Download An International Comparative Analysis of Blood

 An International Comparative Analysis of Blood Collection
Regulations with Evidence-Based Scientific Findings
By
Rachel Weissman
Professor Darren Zinner, Advisor
A thesis submitted in partial fulfillment
of the requirements for the
Degree of Bachelors of Science with Honors
in Heath: Science, Society, and Policy
Brandeis University
Waltham, Massachusetts
May 2015
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Every 2 seconds, someone in the United States (US) requires a blood transfusion. There
is currently no clinical replacement for human blood, leading to a high dependence on volunteer
blood donors for the necessary transfusion products. On average, the donor population
increases by 3% every year. However, the demand for blood products is growing at an annual
rate of 6%, placing the US on a trajectory towards a continuous blood shortage. The donor
population is currently limited by hundreds of eligibility requirements, which are implemented to
protect the donor from adverse reactions, and protect the patient receiving the blood from
transmitted infections. These regulations should be developed using the most current, widely
accepted, evidence-based data. A comparison was completed to analyze the relationship
between peer-reviewed clinical findings, and the US policies developed by the Food and Drug
Administration, AABB (formerly the American Association of Blood Banks), and the American
Red Cross. An additional analysis was conducted between international policies from 15
comparable countries and US’s policies. The US’s policies closely identify with policies
implemented in Australia, Canada, and the United Kingdom (UK). However, the policies
currently in place in the European countries included in the study, France, Austria, Spain, Italy,
Switzerland, the Netherlands, and Germany, more closely reflected available scientific data,
with more lenient policies concerning patient’s, who receive to donated blood, safety, and
stricter policies regarding donor safety. Thus, compared to available scientific data, US policies
are more lenient towards regulations meant to protect the donor, and stricter for regulations
meant to protect the patient receiving the blood. These findings suggest reassessment and
revision of the US blood collection policies to more closely follow current scientific knowledge,
which will greatly increase the blood supply while maintaining safety.
ADR- Adverse Donor Reactions
FTD- First Time Donors
RD- Repeat Donors
TTI- Transfusion Transmitted Infection
ARC- American Red Cross
FDA- Food and Drug Administration
3 Acknowledgements
I have the pleasure of being able to extend my gratitude to so many different people who
took time out of their busy schedules to support me in this accomplishment. First I would like to
thank Professor Darren Zinner. As my thesis advisor, he has supported me as I researched,
analyzed, and wrote this work. His investment in both the research and me was endless.
Without his consistent patience, guidance, trust, and encouragement, I would not have been
able to complete this senior thesis.
In addition to Professor Zinner, Professors Cindy Thomas and James Morris were
invaluable contributors to this work. Along with Professor Zinner, they both expressed their lack
of background in this relatively archaic topic, and yet they were completely willing to take on the
positions of reader, learn along side me, provide unique insights, and sit on my thesis
committee. I am so thankful for all three of these professors and their continued support
throughout this process.
Before starting my thesis, I conducted preliminary interviews of individuals who I felt had
a unique perspective on the topic to help guide me as I began to form my research questions.
Thank you Allison Weissman, Ben Berson, and Mr. and Mrs. Nelson for speaking with me about
their experiences as blood donors. Thank you to Al Vernacchio who is a Sexuality Educator and
spoke with me about the societal effects of some of the deferral criteria, and there relationship
to discrimination, and thank you to Adam Berger a Blood Drive Coordinator at Brandeis, who
spoke with me about the inner workings of a blood drive.
During my research, I reached out to many different professionals involved in blood
collection organizations from around the world. I did not expect the outpouring of interest I
received. I am so appreciative for the kindness of Manel Gasto Rodriguez, of the Blood and
Tissue Bank of Catalonia, Keltie Cameron-Choi, Assistant at Canadian Blood Services, Una
O'Doherty with University of Pennsylvania, Vernice Wright, Membership/Sales Coordinator with
AABB, Shira Katiy, Assistant to Blood Services Director of Magen David Adom in Israel, and
Veronica Gendelman, Director of Magen David Adom in Israel. All of these individuals provided
me with so much data, and aided me in my research process. I am especially grateful for Anne
Eder MD PhD, Executive Medical Officer of American Red Cross, Brian Custer, PhD, MPH,
Associate Investigator of Epidemiology and Health Policy Research at Blood Systems Research
Institute, and Mindy Goldman MD, Director of Canadian Blood Services, who all set aside time
to speak with me about my research. All of these individuals are leading researchers in this
field, and I am humbled by the fact that they were willing to take time out of their day to speak
with me for hours about their research, my research, and provided me with advice and
guidance. There are very few people who have a background in this topic, and I am thrilled I
was able to speak with the top researchers in the world.
I would also like to thank my friends and family for the continued patience and support
throughout this long process. In particular I would like to thank Miriam Fink, Yuya Yoshida, and
Petra Nelson for helping me translate the hundreds of different documents I searched through.
Finally, I would like to thank my parents for the incredible opportunities they have provided me
with. My mother for her unwavering encouragement and reassurance, and my father for always
being their when I needed him, and having an answer for everything.
I am truly so lucky and thankful to have been able to go through this experience with such
an incredible support system.
4 TABLE OF CONTENTS
CHAPTER 1
• Introduction
o Importance of Topic
o Relevance for HSSP
§ Health
§ Science
§ Society
§ Policy
• Blood Components
o Red Blood Cells
o Platelets
o Plasma
• Typology
o Figure 1: Whole Blood, Red Blood Cell and Plasma Donor and Recipients, by
Type
• Blood Borne Infectious Diseases
• Blood Tests and Screening
o Figure 2: Timeline of Blood Test and Screen Implementations
CHAPTER 2
• The US Blood Supply
o Donor Demographics
o Blood Shortages
o Federal Involvement
§ The Food and Drug Organization
§ Advisory Committee
§ Code of Federal Regulations and Guidance to Industry
o Private Involvement
§ AABB
§ The American Red Cross
§ Private Blood Banks, Centers, and Services
• Figure 3: Blood Systems Hierarchy of Associated Blood Services,
Centers and Banks
CHAPTER 3
• Blood Donations
o The Collection Process
o Effects of Deferrals
o Adverse Donor Reactions (ADR)
• Transfusion Complications
o Infectious Transfusion Complications
§ Table 4: National Average of Allogeneic Blood Transfusion Related
Infections
o Non-Infectious Transfusion Complications
CHAPTER 4
• Goal
• Hypothese
• Methods
o Table 5: Regulation Topics Categorized by Purpose
o Categorization
o Study Population
5 o
§ Inclusive Criteria
§ Exclusive Criteria
§ Included Countries and their Blood Collection Organizations
Data Collection
§ Metrics
CHAPTER 5
• Results
o Regulations to Protect the Donor
§ 1. VITALS: Pulse, Blood Pressure, and Hemoglobin
• Pulse
o Figure 6: Required Pulse Range for Donors by Number of
Countries with Regulation
• Blood Pressure
o Figure 7: Lower Limit for Systolic Blood Pressure
o Figure 8: Upper Limit for Dystolic Blood Pressure
o Figure 9: Lower Limit for Dystolic Blood Pressure
• Hemoglobin
o Figure 10: Minimum Hemoglobin Levels by Gender
o Figure 11: Minimum Hemoglobin Levels for Females
o Figure 12: Minimum Hemoglobin Levels for Males
§ 2. AGE: Minimum Age for First Time Donors (FTD), Maximum Age for
FTD, and Maximum Age for Repeat Donors (RD)
• Minimum Age
o Figure 13: Reaction Rate (per 1000 donation) for First
Time and Repeat Donors by Age
o Figure 14: Minimum Age for First Time Donors
• Maximum Age
o Figure 15: Maximum Age for First Time Donors
o Figure 16: Maximum Age for Repeat Donors
§ 3. BLOOD COLLECTION: Estimated Blood Volume, Volume and
Frequency of Donation
• Estimated Blood Volume (EBV)
• Volume and Freqency of Blood Donation
o Figure 17: Maximum Amount of Whole Blood Collected
During a Donation
o Figure 18: Maximum Frequency of Blood Donations for
Females Over 18 Donating 400 mL or More
o Figure 19: Maximum Frequency of Blood Donations for
Males Over 18 Donating 400 mL or More
§ 4. PREGNANCY
• Figure 20: Deferral Period After Childbirth
§ 5. CHRONIC DISEASES: Cancer, Heart and Lung Diseases, and
Diabetes
• Cancer
• Heart and Lung Health Issues
• Diabetes
o Regulations to Protect the Patient
§ 6. EXPOSURE: Tropical Infecions (Malaria, Chagas Disease,
Babesosis, West Nile Virus, Creutzfeldt-Jakob’s Disease, and
Varient Cruetzfeldt-Jakob’s Disease)
6 Malaria Infection and Travel to Malaria Endemic Areas
o Figure 21: Deferral After Travel to a Malaria Endemic Area
• Chagas Disease and Babesiosis
• West Nile Virus
• Increased Risk of Classic Cruetzfeldt-Jakobs disease or
Varient Creutzfeldt-Jakobs disease from Travel, Clinical
Exposures, or Family History
o Table 22: International CJD and vCJD Regulations
§ 7. EXPOSURE TO INFECTIOUS DISEASES: Sexually Transmitted
Diseases (HIV/AIDS and Viral Hepatitis Infections), and Other
Infections (Bacteria, Virus, Fungi)
• Table 23: FDA US Guidelines for HIV and Hepatitis Virus
Exposures
• Direct HIV Exposure
• MSM Exposure
• Sub-Saharan Africa Exposure
• Direct Hepatitis Exposure
o Table 24: Viral Hepatitis A, B, and C Risk Factors,
Prevalence, Indicidence, and Fatalities
o Figure 25: Deferral After Sexual Activity with Hepatitis
Carrier
• Exposure through Broken Skin
o Figure 26: Deferral Period After Peircing in Possibly
Unsterile Setting
o Figure 27: Deferral Period After Exposure to Another
Person’s Blood
o Figure 28: Deferral Period After Tattoo in Possibly
Unsterile Setting
• Exposure through Sexual Activities with High Risk
Individuals
o Figure 29: Deferral Period After Sex with a “High Risk”
Individual by Deferral Length
• Incarceration Exposure
• Clotting Factor Concentrate Exposure and Other
Contaminated Blood Products
• All Exposures
o Figure 30: Deferral Period After Cessation of “High Risk”
Activity by Number of Countries with Regulation
• Other Infectiond
o Figure 31: Deferral Period After Completion of Antibiotics
§ 8. BLOOD QUALITY: Smallpox Vaccination
• Vaccinia Virus from Smallpox Vaccine
o Table 32: Deferral After Receiving the Smallpox Vaccine
by Country
Study-Wide Themes Between US Policies, Scientific Data and International
Policies
§ Policies to Protect the Donor
§ Policies to Protect the Patient
§ Figure 32: Diagram of Policies’ Relationhips to Scientific Evidence and
International Regulations
•
o
7 §
§
Table 33: Summary of Results
Figure 34: Summary of Classification of the Comparison between US
Policies, Scientific Data, and Internaitional Policies
• Key for Figure 34
CHAPTER 6
• Discussion
o Large Discrepancies Between US Policies and Scientific Data
o Large Discrepancies Between US Policies and International Policies
CHAPTER 7
• Policy Recommendations
o Structure of Policy Decision Making and Important Factors for
Consideration
§ Public Health Services
§ Donors Lying
§ Discrimination
o Policy Suggestions
§ High Risk Exposure Policy Suggestions
§ Suggested Wording for Health Histories Questionnaire
§ vCJD Deferral Policy Analysis
§ Protection of Donors Policy Suggestion
§ Travel Regulations for Malaria Policy Suggestion
• Limitations
• Future Studies
• Conclusion
8 CHAPTER 1
Introduction
Importance of Topic
For well over a century, people have relied on collected human blood and products to
treat trauma, blood diseases, and chronic illnesses. There is no FDA-approved synthetic blood
replacement that is capable of transporting oxygen. It cannot be manufactured commercially or
collected from non-human sources. Blood is almost entirely collected from volunteer donors who
altruistically provide this lifesaving treatment to critically ill patients. The critical concern of the
use of blood, beyond its availability, is the possible transmission of pathogenic organisms by
blood to the receiving patient. In the 1960’s, one third of blood transfusion recipients became
infected with viral hepatitis due to contaminated blood. The HIV/AIDS epidemic increased this
problem, further pointing to the need for gold standard blood testing and donor screening. If an
individual is not able to donate blood, due to an exposure or high-risk activity, that individual is
“deferred” from donating blood. Individuals can also be deferred for characteristics that make
them or the recipient higher risk for experiencing an adverse health outcome from the donation
process. The policies that dictate who can and cannot give blood have major effects on the
national supply of blood, and can be detrimental when the number of willing and eligible donors
is exceeded by the number of patients requiring human blood.
Relationship to HSSP
Health
In 2011, blood transfusions were the most common health procedure carried out during
hospitalizations.1 The rate of blood transfusions has increased by 138% since 1997, to nearly 3
million inpatient transfusion recipients, or 12% of all hospitalizations in 2011.1 The safety,
efficiency, and reliability of the blood collection process is vital to maintaining the health of the
country.
9 Science
The driving factor behind blood donor eligibility should be the capacity for technology to
screen out blood that might cause the spread of infections, specifically Hepatitis B Virus (HBV)
and Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV)/ Acquired
Immunodeficiency Syndrome (AIDS), Chagas Disease, Syphilis, West Nile Virus (WNV), and
Human T-Lymphotrophic Virus (HTLV). These tests are constantly being improved and adjusted
to increase the specificity and sensitivity, as well as the detection ability for possible new
infections, or new strains of infections, which could infect the recipient of the blood. The more
specific the screens are, the shorter the deferral times need to be, and the quicker individuals
can rejoin the donor population and begin donating again.
Researchers are also constantly looking for possible ways to develop synthetic blood or
a blood substitute that is able to carry oxygen to remove the need for human donors altogether.
There have been a few possible breakthroughs in the search for an alternative blood source and
some clinical trials have been carried out in the US and the UK. There was even one oxygencarrying substitute that was approved by the FDA, but it was soon retracted due to the
complexity of its use and its substantial side effects. There are many synthetic products
available that are able to fulfill other functions of blood, like hydration and volume. However
there has not been a suitable oxygen carrying substitute to properly replace all of the needs of
the country. Until this replacement is discovered, tested, produced, and made cost-efficient,
patients will continue to depend on donated blood with the capacity to carry oxygen.
Society
Society’s perception of risk is well represented in blood donor eligibility policies and the
acceptable capacity for risk is a major component of policy development. A line must be drawn
where the risk outweighs the need, and vice versa. Deferral periods and lifetime bans remove
huge populations from the donor pool. This is acceptable if it is also removing a proportionate
amount of risk. As risks shrink to the range of one in a million, further reducing risk becomes
10 more and more difficult without the aid of technological breakthroughs. When just faced with
epidemiological information and demographics about risk, removing high-risk populations
becomes the only option.
Policy
Blood donation regulations are partly based on the laws in the Code of Federal
Regulations Title 21 (CFR) and partly based of suggestions from the US Food and Drug
Administration (FDA). The FDA oversees all US blood collection organizations to ensure the
proper safety precautions are in place. The regulations suggested by the FDA are often adopted
fully by collection agencies. Any type of change to the eligibility of donors, the screening
process, or the collection process must be developed as policy and either included in the CFR
as federal law or suggested by the FDA.
Blood Components
Red Blood Cells
Red blood cells (RBC), also known as erythrocytes, transport oxygen collected from the
lungs through the body via the circulatory system.2,3 RBC travel through the pulmonary vein to
the capillaries of the lungs where the oxygen molecules bind with iron, a component of
hemoglobin (Hb), which is the active subunit within RBC. The oxygenated RBC enter the heart
through the pulmonary artery where they are pumped systemically. When the RBC arrive at the
necessary tissue cells, the dissolved oxygen molecules diffuse through the membranes.2 The
RBC then become deoxygenated and continue circulating until they become oxygenated in the
lungs once again. The RBC life span lasts about 120-days and begins with their formation in the
bone marrow, along with white blood cells and platelets, which are all formed from the same
precursor stem cell through a process known as hematopoiesis.4
RBC transfusions are used in many medical situations, including trauma and surgery, as
well as, treatments for chronic blood diseases, like anemia and sickle cell disease.3 RBC
transfusion units are created by centrifuging whole blood and collecting the sedimented RBC,
11 which fall to the bottom of the centrifuge vial due to their high density. This process removes the
majority of the plasma and platelets, which then can be used to create other blood products.
Once RBC are isolated, they can be transfused into another individual. Most studies show RBC
must be transfused within 42 days of collection or they no longer viable.5 Due to the short
lifespan of RBCs, a significant portion of the RBCs in the unit will have reached the end of their
120 day lifecycle. The greater the time between the collection and transfusion, the lower the
quality of the RBC; data suggest this can lead to poorer post transfusion outcomes.6 To
maintain viability, RBC are stored in their liquid state at 6 degrees Celsius or lower.7 However
this constant temperature is only imperative to the health of the RBC after 14 days postcollection. Before that time, the cells are more resilient and can withstand the changes in
temperature that can be associated with transportation.7
Platelets
The smallest component of whole blood, platelets, also referred to as thrombocytes, are
the primary cells involved in the clotting process where they accumulate in the vessel under a
wound to reduce blood loss.8 The importance of platelets can be observed when patients with a
reduced concentration of platelets take longer to stop bleeding after an incision, compared to
those with normal levels.9 Platelets also help to maintain homeostasis within the blood. The
membrane of the platelets are covered with glycoprotein receptors that bind ligands like
fibrinogen, von Willebrand factor, collagen, fibronectin, vitronectin and thrombospondin, all
factors involved in controlling and regulating blood coagulation and clotting.9 Disorders affecting
any of these receptors or ligands can cause increased bleeding time, absence of clots, or
spontaneous changes in blood homeostasis.9
Platelets are used in surgery, but are more commonly included in treatments for cancer
and organ transplants.3 They make up a small portion of the total volume of blood, which is why
many whole blood donations are needed to make up a single transfusion dose. A transfusion
dose is either made up of five units of platelets that have been separated from a whole blood
12 donation, also known as ‘pooled platelets’ or one platelet apheresis donation.8 Storage of
platelets has been a challenge and transfusion units have been shown to be very sensitive to
lack of oxygen, sedimentation, changes in pH, and bacteria growth.10 Consequently, platelets
must be used within 5 days of collection.3,8 This timeline creates a constant demand, and
collection agencies must work quickly to prepare platelets for transfusion. In most cases,
platelets are stored between 20 and 24 degrees Celsius in plastic membrane bags with a
specific surface-to-volume ratio, which allows for adequate oxygen diffusion.10 To make sure all
of the cells in the unit are able to receive oxygen the bags are kept in an agitated state, even
during transportation, to make sure the cells do not sediment and suffocate, causing cell
death.10 Data have shown that exposure to temperatures below 18 degrees Celsius damages
the cells, however, temperatures above this create the perfect environment for bacteria
growth.10 Their susceptibility to bacterial contamination means each platelet unit must be
carefully inspected for safety and quality before transfusion. Using a closed collection system,
where separation and inspection happen within the collection bag and the sample is never
exposed to open air, has minimized contamination risk.10
Platelet transfusions can also include some types of leukocytes, also known as white
blood cells.10 There are five different types of leukocytes separated into two categories:
granulocytes, named for their grain-like sacks of enzymes that digest microorganisms, and
agranulocytes, cells devoid of these sacks. There are three types of granulocytes: basophils,
eosinophils and neutrophils, and two types of agranulocytes: lymphocytes and monocytes.11,12
The major function of all leukocytes is in the immune system. These roles include defenses
against infection from viruses, bacteria, fungi, protists and helminthes.
Plasma
Plasma makes up the majority of the volume of blood, and is the protein-salt liquid
component of blood that is 92% water and contains proteins, glucose, clotting factors,
electrolytes, hormones, CO2, antibodies, and other protiens.13,3 Plasma has multiple functions
13 within the body including transporting cells and other necessary components to the correct
tissue, maintaining blood pressure, blood volume and pH balance to preserve homeostasis, and
facilitating the exchange of minerals like sodium and potassium, which are critical components
to many physiological mechanisms.13 Plasma is the most stable component of blood and can be
stored for up to a year if frozen within 24 hours post-collection.13 Unlike RBC or platelets,
plasma can be treated with solvents or heat to destroy viruses like HIV, Hepatitis B, and
Hepatitis C.13
Donated plasma is often processed into ‘plasma derivatives,’ which are concentrations
of specific proteins found in plasma. Some common plasma derivatives include Immune
Globulins, used to treat very immunocompromised patients like those with X-Linked
Agammaglobulinemia, Factor VIII concentrate, which contains the Antihemophilic Factor (AHF),
and Factor IX concentrate and Anti-Inhibitor Coagulation Complex, both treatments for bleeding
events in hemophilic individuals.13 Plasma is also used to create Cryoprecipitate AHF, also
commonly referred to as Cryo. Like plasma, cryoprecipitate can be frozen and stored for up to
one year after the collection and is manufactured by collecting the precipitate from thawing
plasma.5,3 Cryo contains fibrinogen, factor VIII, factor XIII, fibronectin, and von Willebrand
factor.14 Plasma and plasma derivatives have a wide range of uses, including treating shock and
burn patients, as well as managing bleeding and immune disorders.3 Cryo has much more
specific uses, like treating some chronic blood diseases like hemophilia and Von Willebrand
disease, and it is also the only source for high concentrations of fibrinogen.3
Typology
Blood is physiologically separated into four ABO types (A, B, O and AB) and two Rh
factors (positive and negative). A patient must receive a compatible blood transfusion or they
can experience complications like acute hemolytic transfusion reaction (AHTR) due to ABO
incompatibility (see Transfusion Complications).15
14 Whole blood, RBC, and plasma have different transfusion-compatible blood types. Just
looking at ABO types for RBC, Type O is the universal RBC donor and can have their blood
transfused to any patient regardless of their blood type, while type A and type B can only be
transfused into other individuals of the same type, as well as, AB individuals.2 AB individuals are
universal RBC accepters, but are only able to donate RBC to other AB individuals who can
receive any time of RBC transfusion.2
Plasma donations are the reverse of RBC. Type AB is the universal plasma donor, while
type O is the universal plasma receiver.2 Types A and B can donate plasma to their respective
types in addition to type O, while AB can only receive plasma from other AB individuals.2 Whole
blood includes plasma and RBC so whole blood types can only be transfused to individuals of
the same type.2 For example, type O can only donate whole blood to other type O individuals.
There are no universal donors or receivers for whole blood transfusions.
Rh antigen factors must also be considered for whole blood and red blood cells, but they
do not apply to plasma.2 Each blood type can be Rh antigen factor negative or positive, and are
annotated by and plus (+) or minus (-) sign following the ABO type. Negative means that the
individual’s blood lacks Rh antigens. Negative blood can be donated to both positive and
negative individuals, while positive can only be donated to other positive individuals. This is
necessary because the presence of the Rh antigens will cause a Rh negative individual’s
immune system to attack and kill the RBC, which are chemically associated with the foreign Rh
antigens. The ABO type and Rh antigen factor must be considered and matched correctly
before a transfusion is conducted (Figure 1). There are eight different types of RCB and whole
blood (O+, O-, A+, A-, B+, B-, AB+, and AB-) and four types of plasma (O, A, B, and AB).
Apheresis makes it possible to isolate and remove a specific blood component from an
individual and return the remaining blood back into the body. For example, Red Cell Apheresis,
often referred to as ‘Double Red,’ removes two pints of blood from a donor, one pint at a time,
and separates out the RBC. The machine then returns the rest of the blood, including the
15 plasma and platelets, back to the donor and keeps the RBC. The lost volume is replaced by
saline solution to maintain proper blood pressure and reduce the risk for adverse donor
reactions (ADR). This process can be beneficial because it produces two ‘units’ of red cells to
be given to a donor. It is safer for a patient to receive blood from a single donor, rather than
multiple donors, because it minimizes the possible risks (see Transfusion Complications).
Whole Blood, Red Blood Cell and Plasma Donor and Recipients, by Type, Figure 1
Can Receive Blood From:
Can Donate Blood To:
O+
O-
O+
plasma
O-
plasma plasma
A+
A-
A+
plasma
A-
plasma plasma
B+
B+
plasma
B-
plasma
B-
AB+
AB-
plasma
AB+
plasma
AB-
plasma plasma
Type O blood is the most common in the US, accounting for 45% to 48% of the general
population.2,5 Minority populations, like Hispanic-Americans and African-Americans, have a
higher percentage of type O blood, 57% and 51% respectively.5 O- blood is the most highly
demanded RBC type for medical purposes, because it is the only type of blood that can be used
in emergency situations where the patient’s blood type is unknown.5 Only 7% to 9% of the US
population has O- blood.5,2 Only 3% of individuals have AB+ blood, and while they can only
donate RBC and whole blood to other AB+ individuals, they are universal plasma donors, which
is often used in emergency situations with patients requiring huge volumes of blood and with ill
newborns.2,5
16 Blood Borne Infectious Diseases
Transfusion-transmitted infections (TTI) are infections caused by a blood transfusion
contaminated with bacteria, viruses, parasites, or prions. These types of infections can be
transferred through many different mechanisms, including association with blood cells, free
floating cells in plasma, or introduction of the pathogen via the injection site on the donor’s skin.
Many pathogens are able to survive within stored blood as long as the blood cells are being
kept alive. In many cases, stored blood is the perfect proliferation environment for bacteria,
which are carefully protected through temperature, aggregation, and glucose supplements.
Blood Tests and Screening
One of the main limitations for protecting the national blood supply is the restricted
capacity to test for harmful, and possibly fatal, infectious diseases. This challenge is combated
by strict eligibility practices, implementation of gold-standard tests, and treatments of the blood,
when possible. Blood collection organizations routinely test for 7 infectious diseases: Hepatitis B
Virus (HBV) and Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV)/ Acquired
Immunodeficiency Syndrome (AIDS), Chagas Disease, Syphilis, West Nile Virus (WNV), and
Human T-Lymphotrophic Virus (HTLV).a
The first blood screen was implemented in the 1940’s to test the collected blood for
syphilis.16 While now more sensitive and specific, the same type of screen, an antibody test, is
still currently used to test for syphilis. There has not been a single reported case of transfusiontransmitted syphilis in over 30 years. Antibody testing was also implemented to screen for HTLV
in 1988, HIV in 1985, HCV in 1990, WNV in 2003, and Chagas Disease in 2007. HBV testing
was first introduced in 1971 with the introduction of the B Surface Antigen test (HBsAg). As
technology improved, the Hepatitis B Core Antibody test (HBc) was included in 1986. Nucleic
Acid Testing (NAT), the current gold-standard in blood screening, was implemented in 1999
a Unless otherwise indicated, data for this sections is based on American Red Cross, Blood Testing, accessed 16
August 2014. 17 when it supplemented the Antibody Tests for HCV and HIV. Ten years later, NAT was able to
supplement HBc to test for HBV as well (Figure 2). Both Antibody tests and NAT can have false
negatives in specific cases where individuals are able to “control” their viral load, or in cases
where antibodies have not yet been developed. By including multiple tests for the same
infection, the likelihood of false negatives becomes extremely slim.
HBV NAT (2009)
Chagas Disease (2007)
WNV (2003)
HCV and HIV NAT (1999)
HCV Antibody Testing
(1990)
HTLV Antibody Testing
(1988)
HBc (1986)
HIV/AIDS Antibody
Testing (1985)
HBsAg (1971)
Syphilis Antibody Test
(1940s)
Timeline of Blood Test and Screen Implementations, Figure 2
While blood screening has improved immensely, one insurmountable limitation is the
‘window’ or ‘eclipse’ periods associated with many infectious diseases. The window period is the
amount of time directly after infection when the individual is still contagious but they test
negative on available screens. This is due to the individual’s viral load being too low to detect, or
from the lack of antibodies, which have not had adequate time to develop. The American Red
Cross states their current version of NAT has reduced the average window for HBV and HIV to
between 4 and 7 days. HCV is a little bit more difficult to screen for due to the long window
periods. Using an enzyme immunoassay, HCV infections can usually be detected anywhere
between 4 and 10 weeks after infection, and more than 97% of infected individuals will test
positive using this test 6 months after infection.17 However, HCV can be detected as early as 2
weeks by observing viral RNA through PCR testing. It is also common to observe normal liver
enzymes in individuals with chronic HCV for over a year after infection.17 Collection agencies
must depend on strict eligibility regulations to address the window periods.
During the collection, several small sample tubes are filled along with the unit of whole
blood. Most blood collection organizations conduct their screening using a process known as
18 ‘mini-pooling.’ A testing facility will combine, or pool, of approximately 16 different samples.16
The mixture is then tested for each of the infectious diseases. If each test is negative, then all
16 donations are cleared. If the pool tests positive for one of the infections, the 16 donations are
split into two groups of 8 and new pools are made and tested. The samples included in the
mixture that tests negative are cleared. The donations involved in the positive mixture are
divided into two new pools of 4 and tested again. This process continues until the positive
donation is identified. Mini-pooling increases the efficiency of blood screening by up to 93%, by
removing the need to test each donation individually for all 7 infectious diseases.
19 CHAPTER 2
The US Blood Supply
Donor Demographics
There are 30 million blood components (whole blood, plasma, platelets, RBC or Cryo)
that are transfused every year in the US.5 Every 2 seconds, someone in the US requires a blood
transfusion, totaling over 40,000 blood transfusions a day.5 A collected whole blood donation is
approximately one pint of blood, but the average whole blood transfusion into a patient requires
three times that amount. It is possible for a trauma victim to need 100 pints of blood over the
course of their treatment.5
It is estimated that 41.0% of the US population is eligible to donate blood, totaling 122
million Americans.18 However, only 9.2 million Americans donate each year.5 Each whole blood
donation, which contains one pint of whole blood, can produce up to three different blood
products.5 Individuals can also donate specific blood components like RBC, plasma, or platelets,
through apheresis. Apheresis donations have different eligibility requirements, which are
implemented to reflect the necessary characteristics of the specialized equipment. While
apheresis donations can be very beneficial in some cases, whole blood donations are by far the
most common type of donation.
Blood Shortages
The increase in demand for blood is associated with the increase in complicated
treatment plans for conditions like cancer and organ transplants. These complex medical
interventions require more frequent transfusions or human blood components included in the
care path. In September of 2014, the US experienced one of its worst blood shortages, with the
American Red Cross supply 40,000 units below their daily need.19 This shortage was thought to
be due to the difference in annual growth trends between donors and patients needing
transfusions, 3% and 6% respectively.19 Shortages not only put individuals at risk, but also
make entire communities more vulnerable to fatalities during natural disasters or accidents. In
20 situations where blood cannot be supplied to an unexpectedly large group, it must be rationed.
Frequently, elective surgeries must be canceled or postponed due to lack of available blood.19 A
study published in 2010 by the American College of Surgeons has found that elective surgeries
that are postponed after the patient has been admitted into the hospital increases their risk of
infections and their direct medical costs.20 A prospective study completed in Canada concluded
that the risk for death increases the longer individuals must wait for coronary artery bypass
grafting (CABG), one of the most common elective surgeries.21 Blood shortages may not directly
cause fatalities, however, the long-term effects on traditional treatment paths can have
detrimental outcomes for Americans seeking healthcare. Additionally, if the demand for blood
continues to increase at a faster rate than the supply, the outcomes will continue to grow in
severity.
Federal Involvement
The Food and Drug Administration
The Food and Drug Administration (FDA), part of the U.S. Department of Health and Human
Services, oversees all federal interests in food, tobacco, and medical products, which include
drugs, medical devices, and human blood and tissue products. The regulations regarding blood
and blood products fall under the jurisdiction of the Center for Biologics Evaluation and
Research (CBER). CBER’s mission is: “To ensure the safety, purity, potency, and effectiveness
of biological products, and cells, tissues, and gene therapies for the prevention, diagnosis, and
treatment of human diseases, conditions, or injury.”22 CBER creates documents to reflect
evidence-based best practices for safety and efficiency by conducting their own research,
monitoring external and privately conducted research, carrying out surveillance on all aspects of
the market, and employing specialists to analyze necessary data. One of the many goals of
CBER’s office of Vaccines, Blood and Biologics is to regulate and establish standard practices
for the collection of blood and blood components to be used for human transfusion.22
Additionally, CBER develops regulations that apply to the treatment of the blood products
21 themselves, including storage practices, quality standards, screening processes, and bestpractice product preparations for transfusion.23 CBER is also responsible for enforcing
regulations, investigating and monitoring all accident and error reports, and inspecting relevant
organizations and establishments, like blood collection organizations.23 The development of
CBER’s regulations is conducted through multiple channels including Advisory Committees,
input and recommendations from the industry, and collaboration with necessary public health
organizations, both private and public.
Advisory Committee
The Blood Products Advisory Committee was mandated by the Federal Advisory
Committee Act to advise the Commissioner of Food and Drugs and is a private external group
of specialists who act as support for CBER in analysis of current and relevant data.24 The Blood
Products Advisory Committee is made of the Chair of the Committee and 16 other voting
members who are chosen by the Commissioner and represent all sectors of the blood
collection, storage, processing, and supply markets. This includes individuals specializing in
medical and biological disciplines like hematology, immunology, surgery, internal medicine,
biochemistry, and epidemiology, and those involved in the more technical and logistical aspects
of the processes, like engineers, physical scientists, computer technology specialists,
statisticians, and blood bankers.24 One voting member, who is usually chosen by a consortium
of consumer-oriented organizations, represents the general public and consumer interests.24
The Committee may also choose to include one non-voting member who represents industry
interests to involve their perspectives in discussions.24 This Committee provides expert analysis
of all technical data to help insure that all requirements and guidelines reflect the best possible
methods to keep the market as healthy and efficient as possible.
Code of Federal Regulations Title 21 and Guidance to Industry
There are two sets of FDA publications that include regulations related to the blood
collected and distribution process. The Code of Federal Regulations (CFR) Title 21 includes all
22 mandatory regulations that are federally enforced. They apply to any organization, public,
private non-profit, and private for-profit, which collects, supplies, stores, or distributes blood and
blood products. CFR covers a limited number of topics and focuses on the most technical
aspects of the system, like gold standard tests to use during the blood screening process, and
the proper storage temperatures for each component of blood.25
The Code of Federal Regulations Title 21, Blood Related Topics Addressed: 25
• Section 600: Biological Products: General
• Section 606: Current Good Manufacturing Practice for Blood and Blood
Components
• Section 607: Establishment Registration and Product Listing for Manufacturers of
Human Blood and Blood Products
• Section 610: General Biological Product Standards
• Section 630: General Requirements for Blood, Blood Components, and Blood
Derivatives
• Section 640: Additional Standards for Human Blood and Blood Products
• Section 660: Additional Standards for Diagnostic Substances for Laboratory
Tests
• Section 864: Hematology and Pathology Devices
• Section 866: Immunology and Microbiology Devices
The mandatory and enforced regulations found in the CFR use specific language, like
“shall” and “will,” to differ them from the second type of blood market related publication, the
Guidance for Industries.25 The guidance documents use “should”, “can” and “may” to reflect
these recommended regulations. While not mandatory, most collection agencies tend to
implement them immediately after their publication. The FDA states the guidance documents
are a summary of the “agency’s current thinking” on each specific topic.26 Each guidance
document begins with an official statement clarifying that the publication, “does not create or
confer any rights for or on any person and does not operate to bind FDA or the public.”26 They
continue on to say that alternative approaches are possible and may be used as long as all
regulations satisfy the requirements enforced by CRF 21.26 The guidance documents include
large sections of background material and “rationale” sections to lay out the thought process
behind each new suggested regulation.27 They also include any predicted implications these
changes might have on the market.27 Despite the guidelines being optional, each organization’s
23 set of guidelines must first be approved by the FDA before they may enter the market. The FDA
may reject the proposed guidelines if for any reason they do not represent the best possible way
to protect donors and patients. Due to the FDA oversight over all collection agencies, there is
very little variation seen between collection agency’s regulations in the US.
Private Involvement
AABB
AABB, formally known as the American Association of Blood Banks, is a private
organization whose primary goal is to research and develop standards for transfusion medicine.
All those involved in the process of collection, storing, and distributing donated blood can join
AABB as members and go through accreditation programs to be labeled AABB approved. AABB
institutional members consist of 869 transfusion services, 210 blood centers, 217 hospital blood
banks, 164 specialty facilities, and 69 corporate affiliates.28 The mission of AABB is to advance
“the practice and standards of transfusion medicine and cellular therapies to optimize patient
and donor care and safety.”29 AABB began their work and published their first issue of
Standards for Blood Banks and Transfusion Services in 1957.30 Compliance with these
standards is voluntary but reflect what AABB views as best practices.30 In addition to developing
and publishing the market standards, AABB conducts research through the National Blood
Foundation and publishes a peer-reviewed scientific journal, Transfusion, which is “the primary
international vehicle for publication of scientific, technical and administrative papers relating to
blood banking; transfusion medicine; hematopoietic; cellular and gene therapies; and tissue
transplantation.”30 Both of these services have been valuable assets to the blood collection,
storage and distribution research climate by providing the needed financial support and avenue
for publishing relevant data.
AABB developed the National Blood Exchange in 1953, which is a service that has
attempted to create a network of blood sharing between unaffiliated facilities to combat
shortages and surpluses across the country.31 This is the largest resource-sharing program to
24 exchange blood components, and they coordinate the distribution of over 185,000 transfusion
units annually.31 The goal of this program is to increase efficiency and reduce waste, however,
at this time it is only responsible for coordinating less than 1% of the nation’s blood meant for
transfusions.5,31 AABB charges a 1% transaction fee from both buyer and seller, which brought
in over $600,000 in FY2013.28,31 They have recently developed an online system where blood
banks and hospitals can manage their supply and demand, further increasing the efficiency and
interconnectedness of the market. This exchange improves national access to blood, especially
during times of emergency shortages, like natural disasters. For situations that require this kind
of assistance, AABB dispatches their Interorganizational Task Force on Domestic Disasters and
Acts of Terrorism to transport the necessary blood products as quickly as possible to the
affected areas without jeopardizing the supplying blood bank’s patrons.31 AABB influences the
blood collection and distribution market in many different ways including standardization
techniques, best practice education, outreach, research, encouraging utilization of existing
resources, and combating area shortages. However, they are only one of the major private
influencers involved in the blood collection and distribution process.
The American Red Cross
The American Red Cross (ARC) blood collection and distribution program began in 1940
as one of the services provided to fulfill their mission to prevent and alleviate suffering both
nationally and internationally.32 The blood service program is only one of the five key main
services ARC provides. The other four being international services, disaster relief, support for
America’s military families, and health and safety services like first aid and CPR training.32 ARC
is the largest private blood distributor, supplying on average 40% of the nations blood to
approximately 2,700 U.S. hospitals.5 The majority of the blood is collected through more than
200,000 mobile blood drives ARC conducts annually with over 50,000 community sites.5 These
mobile blood drives are held at high schools, colleges, community centers, military bases,
offices, and places of worship. The remaining 20% of the blood is collected from ARC’s
25 permanent blood collection centers.5 During FY2013, ARC collected 5.7 million units of blood
from 3.3 million volunteer donors.32 These units of blood were manufactured into over 8 million
blood products, which were than distributed nationally.32
Private Blood Banks, Centers, and Services
Blood banks, blood centers, and blood services are all private blood collection
organizations operating independently or associated with regional hospitals. In most cases,
blood centers are locations where blood is collected but then sent to another location for
screening and storage. Blood banks are usually collection and storage facilities; they are also
commonly the midpoint between blood centers and hospitals or transfusion services. Blood
services are collection agencies with more than one location. These larger organizations usually
deal with a cohort of hospitals who they are responsible for supplying entirely. The distinction
between centers, banks, and services is not always clear, many centers and banks are privately
run while being associated with a larger service. This is common practice when services
purchase or buy the rights to individual centers or banks to increase their coverage. For
example, Blood Systems, one of the largest private collection organizations in the nation,
consists of one blood service and four blood centers, and spans 13 states with 52 collection
locations.33 Some of these partnerships are affiliations, which allows more independence within
the hierarchy, while others are acquisitions. In 2013, Blood Systems collected 924,695 whole
blood units to be transfused to patients in regional hospitals.33
26 Blood Systems Hierarchy of Associated Blood
Services, Centers and Banks, Figure 3
United Blood Services of AZ United Blood Services of ND United Blood Services of CA United Blood Services of LA United Blood Services of MS United Blood Services of MT United Blood Services United Blood Services of NV United Blood Services of NM United Blood Services of SD United Blood Services of TX United Blood Services of WA Blood Systems Blood Centers of the PaciSic United Blood Services of WY Blood Centers of the PaciSic Bay Area BonSils Blood Center Blood Centers of the PaciSic East Bay Blood Centers of the PaciSic North Bay Lifestream Blood Centers of the PaciSic North State Inland Northwest Blood Center 27 CHAPTER 3
Blood Donations
The Collection Process
The collection process is the first method collection organizations use to protect patients
that will receive the blood from blood borne infections. They do this by screening donors for the
possibility of transmitting an infectious disease through background questions and health history
questions. When a donor arrives at a collection site, they are given booklets to read, which
provides them with safety information, explains the collection process, and gives them
information about ‘self-deferrals.’ Self-deferrals are a list of possible exclusion factors, like
weight, medications, diseases, and behaviors, that would immediately restrict an individual from
donating. This information is given to the donors to reduce the amount of resources and time
wasted on an individual that is unable to donate.
Once they enter into the health histories section, nurses test their vital signs, ask them
questions about their past behaviors and exposures, and try to identify anything that would
cause the donation to negatively effect them or the patient that receives the blood. During this
time, nurses also assess the ability for the individual to donate blood safely and withstand the
blood loss. Collection agencies aim to minimize the number of negative ADR experienced. If the
individual is eligible to donate they will move to the second part of the process, where a
phlebotomist disinfects the donor’s arm and collects a pint of whole blood. The collection usually
takes about 10 minutes, and is dependent on the donor’s blood pressure and hydration level.
Once the donation is complete the blood is sent to a blood bank to begin testing, the second
half of how transfusion patients are protected, and the donor is given refreshments to increase
hydration and blood sugar. Most collection sites require the donors to stay on the premises for
at least 15 minutes following donation. This is done to monitor any ADR, which can be dealt with
by the nurses in the controlled setting of the blood collection site.
28 Effects of Deferrals
Deferrals that appropriately protect the donor or patient from ADR are completely
necessary to have a safe and well functioning supply. However, if current policies are causing
deferrals that are preventing eligible donors from donating the sustainability of the national
supply comes into question. A study observing the effects of temporary deferrals found that only
25% of first time donors will return to try to donate again, if they were temporarily deferred. This
quarter return rate is compared to the 47% of first time donors that will return to donate again
after a successful first donation. This study explains the effects of different temporary deferrals
on the donor population, concluding that deferrals of any kind, even short 24 hour deferrals, will
greatly decrease the donor population, not just at the time of deferral but for all future
donations.34 This information confirms the need to remove any unnecessary deferrals to
maintain the current and future national blood supply.
Attention has been turned towards ways to increase the minority presence in the blood
supply. One motivation for this is the demand for blood that carries the sickle-cell trait, which is
found primarily in people of African descent.18 Another important consideration is the high
prevalence of type O blood in both African American and Hispanic donors compared to white
donors.18 These efforts are being skirted by the high deferral rates for minority populations. A
study comparing donor centers over a 3 year period found 12.4% of white presenting donors
were deferred compared to 21.3% of Asian presenting donors, 19.7% of Black presenting
donors, and 19.5% of Hispanic presenting donors.35 These results indicate that simply an
increase in minority donor populations may not solve their contribution to the supply.18 Both
Hispanic and African American individuals have significantly lower average hemoglobin levels
compared to individuals of European and Asian descent. This leads to a substantial difference
between deferral rates due to low hemoglobin for African Americans, Hispanics, and white
presenting donors, 11.97%, 6.20%, and 3.65% respectively.18 Other discrepancies are deferrals
due to STI’s, prison, tattoos, and IV drug use, all more frequent in minority populations.18 The
29 majorities of these deferrals are for at least 12 months, and disproportionately effect the minority
populations.
Adverse Donor Reactions (ADR)
During a donation, the body is losing a significant volume of blood over a short period of
time, potentially causing the body to react as if it is experiencing an acute injury. Through a four
reflex pathway, including chemoreceptors and baroreceptors, the sympathetic nervous system
triggers the release of epinephrine and norepinephrine. On the most basic level, hemorrhage
causes increased heart rate, increased contractility, and arteriolar and venous constriction. This
is one reason why some donors react badly to the donation process and will experience ADR
due to the rapid drop in blood volume.
Another source of ADR is the physiological manifestation of anxieties about the donation
process, and hemophobia, also known as the fear of blood. Fainting due to blood loss is a trait
that researchers believe adapted to respond and protect the body against anticipated blood
loss.36 Loss of consciousness causes blood to travel away from the extremities to the head to
restore oxygen flow to the brain.36 The most common type of fainting is vasovagal fainting,
which is brought on by a trigger, like standing up quickly.37 It can also be a response to an
emotional trauma, this type of fainting is termed “emotional fainting” because it is a physiological
response due to a perceived outcome, rather than an active injury.36,37Many studies have found
that individuals who express more fear about the donation process, or fear of blood in general,
are at a higher risk to experience ADR, especially dizziness and loss of consciousness.38,36 A
study conducted in 2012 suggested that assessment of a donor’s fear may be a better
predictive measure for ADR than any other donor characteristic, like age, weight, or pulse.39
Females, first time donors (FTD), and young donors are all at an increased risk for emotional
fainting.40
ADR affect the likelihood for donors to return and continue donating. This trend is
especially evident for FTD. Approximately 30% of FTD who experience a mild ADR and 20% of
30 FTD who experience a moderate or severe ADR will return to donate again, compared to 40%
to 47% of FTD who will return after having no adverse effects.41,18
ADR are categorized as mild, moderate and severe. Mild ARD are the most common
and can include:
•
•
•
•
•
•
•
•
•
•
increased respiration,
rapid pulse,
pallor and mild sweating,
bruising at donation site,
anxiety,
dizziness,
continuous yawning,
nausea or vomiting
arm soreness,
or tingling of the arm or fingers.42
Moderate ADR can include loss of consciousness, repeated periods of unconsciousness, slow
and/or faint pulse, and shallow respirations.42 Moderate ADR can lead to more severe outcomes
if an individual injures himself or herself when losing consciousness. A severe ADR
encompasses any of the other symptoms, in conjunction with prolonged periods of
unconsciousness; they can also include convulsions, usually following periods of loss of
consciousness.42
By far the most unlikely post-donation complication is death. The FDA requires all
deaths connected to the collection or distribution of blood to be reported and investigated.
Between October 1st, 2012 and September 30th, 2013 there were 7 post-donation fatalities.43
Investigations found that two of the deaths were unrelated to the donation, despite the close
time proximity, and adequate evidence absolved any connection to the collection process.43 For
the remaining five fatalities, a “temporal link” to blood collection was identified but a causal
relationship could not be established.43 During this time frame, there were no fatalities
definitively linked to the blood donation process.43
To avoid ADR, a list of physical characteristics is used to identify those at an increased
risk. This includes blood pressure and pulse to ensure heart health, height and weight to
31 calculate estimated blood volume (EBV), hemoglobin levels, temperature, and age. A study
published in 2013 measured the overall demographic breakdown of ADR and identified the most
common symptoms post-donation. The study population was composed of 1,371 male FTD,
2,080 female FTD, 7,142 male repeat donors (RD) and 7,025 female RD.44 This study employed
a survey that assessed both systemic ADR (fatigue, feeling faint, dizziness, loss of
consciousness, etc.) and donation site ADR (bruising around needle site, arm soreness,
tingling, numbness or weakness in fingers or arm, etc.). This study found that 32% of FTD and
14% of RD experienced some kind of ADR.44 For every race, age, and type of reaction, all ADR
were most common in female FTD, and least common in male RD. “General arm symptoms”
were the most common ADR in all demographics, effecting 28.0% of female FTD, 16.2% of
female RB, 13.4% of male FTD, and 8.5% of male RD.44 When the data was controlled for age,
results showed a significant association between ADR and young age. Donors ages 17 to 22
were 8.1 times more likely to experience systemic symptoms, and 4.1 times more likely to
experience arm symptoms, compared to donors 50 and older.44 The strongest association
identified was the increased likelihood of any type of ADR and EBV, calculated using the sex,
height, and weight of a donor. The study found, 17.1% of female donors who’s EBV was less
than 3.5 L experienced a systemic reaction, compared to 7.3% of female donors whose EBV
was greater than 4.5 L.44 The study concluded that risk factors for ADR are young age, FTD,
low EBV, and the female sex.
The American Red Cross (ARC) states syncopal, or fainting, reactions occur between
0.13% and 0.27% of all donations.45 A major concern surrounding loss of consciousness is not
the reaction itself but possible injuries the event may cause. On average, 8.8% of all syncopal
reactions lead to an injury.45 Age and likelihood of a syncopal reaction causing an injury display
an inverse relationship, with the younger donors experiencing a significantly higher rate of
injuries due to fainting compared to the older donors.45 Females and FTD are also more likely to
experience an injury due to a syncopal donor reaction compared to males and RD.45
32 Transfusion Complications
Like any medical intervention, patients receiving blood transfusions are at risk for
adverse effects due to the treatment. There are many precautions put in place to avoid as many
transfusion complications as possible, including a closed and sterile collection system, strict
eligibility requirements, and extensive blood testing. Transfusion complications can be
categorized as infectious complications, which are caused by the donor passing along a virus,
bacteria, parasite, or fungi via the blood to the patient, and non-infectious complications, which
are due to a patient’s adverse physiological reaction to the transfusion. Transfusion transmitted
infections (TTI) can be avoided by blood testing and extensive screening of blood donors. Noninfectious transfusion complications are avoided by preventive care prior to the planned
transfusion and are usually addressed with general supportive care and observation.
The most common causes of transfusion related mortality are the patient’s physiological
response to the foreign blood. These conditions include transfusion-related acute lung injury
(TRALI), hemolytic transfusion reaction, and transfusion-associated circulatory overload
(TACO). These adverse outcomes are not due to the quality or source of the blood, but rather
the transfusion process itself. Therefore, they cannot be avoided by changes in donor eligibility
or the collection process. Reducing these reactions can be done in a clinical setting by
identifying high-risk patients and increasing evidence-based practices. A study conducted by
UCLA in 2011 found that less than 15% of allogeneic blood transfusion-related (ABT-related)
deaths were caused TTI.46 During FY2012, the FDA reported three ABT-related deaths due to
infections from contaminated blood.43
Infectious Transfusion Complications
Screening and preventative measures for viral infections have been increasing both their
specificity and sensitivity as new threats are identified and technology improves. Transmission
risks for HIV, HBV, HCV, and HTLV have all been substantially reduced with the implementation
of Nucleic Acid Testing (NAT).47 When screening is not feasible for specific viruses, other
33 techniques are employed to protect the patient from viral infections. For example,
cytomegalovirus (CMV) is a major concern for immunocompromised patients, so all high-risk
patients receiving blood transfusions are given specially prepared CMV-seronegative or
leukocyte-depleted blood products.47
An area where there is still substantial risk for infection is bacterial contamination. Often,
the source of the bacteria is from issues with storage and transportation, rather than from the
donor. Platelets require the most specific and complex storage environments due to their
fragility when separated from whole blood, which is why they are most likely to be contaminated
with bacteria. Other areas of concern, which are addressed through donor eligibility, are
protozoal infections (i.e. Malaria, Chagas and Babesiosis) and prion infections (i.e. vCJD).47
Table 4: National Average of Allogeneic Blood Transfusion Transmitted Infections (TTI)
Infection
HIV
HBV
HCV
HTLV
Bacterial infection from platelet transfusion
Bacterial infection from RBC transfusion
Transmission Risk Rate
0.5: 1,000,000
2-5: 1,000,000
0.72: 1,000,000
0.5: 1,000,000
20: 100,000
3.3: 100,000
Sources: Stramer SL. Arch Pathol Lab Med. 2007;131:702-707. Zou S, Stramer SL, Notari EP, et al. Transfusion.
2009;49:1609-1620. Dodd RY, Notari EP, Stramer SL. Transfusion. 2002;42:975-979.
Non-Infectious Transfusion Complications
There are many different types of non-infectious transfusion complications. These can
range from mild and relatively common, to severe and life threatening. The majority of the
complications are due to the body’s response to the introduction of foreign cells. There are
limited prevention methods because a body’s response is difficult to predict, rather many
responses focus on supportive care to reduce any potential long-term damage. A nearly
exhaustive list of possible non-infectious transfusion complications can be found in the
appendix.
34 Acute hemolytic transfusion reactions (AHTR) can be life-threatening depending on the
amount of blood transfused, the rate at which the blood was administered, and the health of the
patient’s kidneys, liver, and heart.48 AHTR is caused by a patient receiving a transfusion that is
an incompatible blood type. AHTR is a very serious complication and requires immediate
medical attention where the primary goal is to maintain blood pressure, which may plummet
during an AHTR event due to uncontrolled bleeding from mucous membranes and open
wounds.48 While rare, AHTR has one of the highest mortality rates for transfusion related
complications, highlighting the importance of correct blood product typing.15,48
Not all long-term effects of blood transfusion are understood. Some studies have shown
a link between repeated transfusions and cancer, indicating that transfusions might play a role
in increasing an individual’s susceptibility to cancer.15 Researchers hypothesize a relationship
like this might be due to the suppression of the host’s immune system, which is necessary for
successful transfusions, but also necessary for attacking mutated cancerous cells.15 The
implications of microchimerism, a situation where foreign cells remain within the host for many
years, are not well known either.15 Microchimerism is usually only seen in patients who have
received massive transfusions, it is estimated that it can affect as much as 10% of this
population, and the foreign cells may make up as much as 5% of the host’s circulating white
blood cells.15 This is a concern because graft-versus-host disease, autoimmune disorders, and
inflammatory disorders are all possible consequences of microchimerism.15 Additionally, several
studies conducted retrospectively have resulted in an association between transfusions and an
increased risk of renal injuries.15
35 CHAPTER 4
Goal
The goal of this study was to empirically examine the variation of US federal guidelines
and regulations associated with the deferral of donors. Donors are deferred if they have been
exposed to something that might put the individual receiving their blood at risk, or if the donor
themselves are at risk for experiencing an ADR. Regulations should reflect the best possible
way to achieve the desired outcomes in production and efficiency, which is reducing as much
risk as possible to both the donor and the patient, while still maintaining a stable blood supply.
Many policies have been implemented to address the scientific uncertainty and risktolerance of the public at the time they were enacted. Since then, new scientific findings or
screening breakthroughs have changed the true risk rates of possible contamination. However,
policy inertia often makes it difficult to update regulations, especially because public perception
may not align with the implications of evidence-based studies. Some groups, organizations, or
countries may choose to update specific regulations when there is overwhelming evidence in
addition to public support, while others may only be influenced by either public opinion or
scientific data. Regulations concerning the blood collection process vary by country’s
government policies, and are not uniform internationally.
Hypotheses
H1: Guidelines which closely align with available data and appropriately reflect the risk rate and
transmission rate will be associated with less variation across international countries, and be the
more common regulation observed.
H2: Greater variation across organization’s guidelines will be seen when the scientific risks have
not been quantitatively summarized into transfusion-transmitted risk rates due to lack of
research or gaps in scientific knowledge.
H3: Strict US policies, which have been clouded by non evidence-based information, will be
more likely to differ from international regulations. These situations are most commonly
36 associated with exposures and risks that have been historically difficult to research, control,
measure, or screen, or carry a large social stigma.
H4: Guidelines that do not have concrete scientific data will provide information about the level
of caution a country decides to take towards protecting the donors or patients receiving the
blood.
H5: Looking at all regulations, there will be less variation between countries whose guidelines
consistently represent current scientific knowledge and greater variation between countries who
are stricter or more lenient than scientific evidence suggests.
Methods
The current FDA guidelines and regulations associated with each risk factor will be
identified and relevant background information will be provided. The regulations are separated
into two categories, those to protect the donor from having an ADR, and those that protect the
patient from contracting any type of TTI.
Regulation Topics Categorized by Purpose, Table 5
Protect the Donor
• Pulse
• Blood Pressure
• Hemoglobin
• Minimum Age for FTD
• Maximum Ages for FTD and RD
• Estimated Blood Volume
• Volume of Donation
• Frequency of Donation
• Pregnancy
• Cancer
• Heart and Lung Health Issues
• Diabetes
Protect the Patient
• Risk of TTI:
o Malaria
o HIV/AIDS
o Hepatitis Viruses
o Classic Cruetzfeldt- Jakobs
and Variant Cruetzfeldt
Jakobs Disease
o Chagas Disease
o Babesiosis
o West Nile Virus
o Other Infections
The FDA guidelines all included their reasoning for suggesting each guideline as well as the
expected implications. This reasoning was compared to the data synthesized from scientific
papers. Peer-reviewed scientific articles were analyzed to identify experimentally collected,
evidence-based data applicable to the regulation. This included incidence, prevalence,
37 transmission rate, available screening, true risk, infectious period, latent periods, and
demographics. Combining this information, the quantitatively collected risk for each threat was
found. This data was then compared to the US federal policies to identify how closely the FDA
policies reflected the available scientific data.
Categorization
•
•
•
•
If the FDA policies reflected the scientific data, they were categorized as appropriate.
If the FDA policies were more cautious then scientific data suggested it should be, they
were categorized as strict.
If the FDA policies were less cautious then scientific data suggested it should be, they
were categorized as lenient.
If there were no FDA policies that addressed an identified risk to the donor or patient,
that topic was categorized as absent in addition to one of the three above classifications
to assess the necessity of the existence of the policy.
Variation within the US between collection agencies is minimal. This is due to the US
approval process for collection organizations, which is monitored by the FDA. While the majority
of the details and metrics involved in determining eligibility are outlined within non-mandatory
and unenforced guidance documents, almost all organizations choose to follow their
recommendations in their entirety instead of finding alternate guidelines which fulfill the
requirements enforced in CFR Title 21. The FDA approval process is done to make sure each
organization is accounting for all of the necessary risk factors. While the FDA guidance
documents are not enforced, the FDA can still deny any proposed regulation that deviates from
their guidelines if they feel they do not adequately protect the patient or donor. Consequently,
this study focused on comparing US policies to those of other countries.
Study Population
Inclusive Criteria
Countries were included if they fit the following criteria:
1. Was within the top 50 countries with high human development, as defined by the United
Nations Human Development Index (HDI) 49
38 a. HDI is “a composite index measuring average achievement in three basic
dimensions of human development- a long and healthy life, knowledge and a
decent standard of living.”49
b. See appendix for list of the top 50 on the HDI
2. Was one of the top 30 countries in health care spending per capita, this reflected all
countries who spent at least US $1,950 per capita.50
a. Total health expenditure is the sum of public and private health expenditures
compared to the total population. It includes health services like preventative
care, curative care, family planning, nutrition and health activities, and
emergency health services. It does not include spending on water and
sanitation.50
b. See appendix for list of countries with health expenditure over US $1,950 per
capita.
3. Had a population of over 7 million people.51
US federal regulations and guidelines were analyzed against international collection
agencies of comparable standards. Comparable standards was defined as being the collection
agency that supplies the largest percentage of blood meant for transfusion processes in each
country in the study, as well as having met the requirements outlined in the inclusive and
exclusive criteria.
I identified countries with comparable demographics, populations, and risk factors to the
US, based on the Human Development Index (HDI) in the belief that similarly-developed nations
should have similar access to the necessary blood tests and collection infrastructure. This was
done to control for countries whose regulations reflect their technological capability, rather than
their idea of gold-standard safety precautions and the country’s risk tolerance. To insure
independence in observations, only countries with their own independent blood collection
organizations were included. Many small countries adopt neighboring country’s regulations and
policies instead of developing their own national standards. For example, Ireland uses the UK’s
policies. These criteria were accounted for by only including countries with 7 million people or
more. The last necessary characteristic for comparison I included is an equivalent amount of
spending for healthcare. This factor ensured countries had a similar view on health spending
39 per capita and results were not be skewed by poverty stricken countries whose blood supply
reflected lack of access to medical care rather than their volunteer donor population.
Inclusive criteria includes: Australia, Switzerland, the Netherlands, United States, Germany,
Canada, Sweden, United Kingdom, Japan, Israel, France, Austria, Belgium, Italy, Spain, Greece
Exclusive Criteria
The above countries were excluded from the study if there were no collection
organization that supplied at least one third of the nation’s blood. This was done to ensure an
adequate source of data that reflected the nationally policies on blood collection. The collection
agencies that were included were the largest blood collection organization in each country.
These criteria removed Greece, who relies primarily on surrounding countries for not only their
policies, but also a portion of the blood products themselves.
Included Countries and their Blood Collection Organizations
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Australia- Australian Blood Services
Austria- Osterreichisches Rotes Kreuz (Austrian Red Cross)
Belgium- Rode Kruis (Belgium Red Cross)
Canada- Canadian Blood Services
France- Etablissement Francais du Sang
Germany- DRK Blutspendedienst
Italy- Associazione Volontari Italiani Sangue (AVIS)
Israel- Magen David Adom
Japan-日本赤十字社 / Nihonsekijūjisha (Japanese Red Cross)
Spain- Banc de Dang I Texitits
Sweden- GeBlod
Switzerland- Blutspende Srk Schweiz (Swiss Red Cross)
The Netherlands- Sanquimn Bloedvoorziening
United Kingdom- National Health Services Blood and Transplants
United States- American Red Cross (ARC)
Data Collection
The eligibility data was collected from the included collection agency’s websites. If the
website did not have all of the necessary information, the agencies were contacted individually.
If information was still unavailable on that specific topic it was indicated on the data table by
40 shading out the box (see Appendix) and that country was excluded from the comparison for that
specific policy.
Metrics
Variation was defined as:
1. Any difference in deferral time over 24 hours for any identified risk.
a. i.e. a lifetime deferral versus a 12-month deferral for the same exposure, or a two
day deferral versus a one day deferral for the same risk
2. Any deviation between allowed ranges for measured vital signs.
a. i.e. allowed pulse range from 40-90 bpm versus 50-100 bpm
3. A absence of an applicable regulation for a factor that is addressed in another country as
a risk and has deferral times associated with its exposure.
a. i.e. 12-month deferral for use of clotting factors versus no stated or implemented
regulation concerning clotting factors
Graphs and Figures
All data used to create the following graphs, figures and tables was gathered from the following
organizations:
Australian Blood Services, Osterreichisches Rotes Kreuz, Rode Kruis, Canadian Blood
Services, Etablissement Francais du Sang, DRK Blutspendedienst Niedersachsen, SachsenAnhalt, Thuringen, Oldenburg und Bremen, Associazione Volontari Italiani Sangue (AVIS),
Magen David Ado, 日本赤十字社 / Nihonsekijūjisha, Banc de Dang I Texitits, GeBlod,
Blutspende Srk Schweiz, Sanquimn Bloedvoorziening, National Health Services Blood and
Transplants, American Red Cross, United States Food and Drug Administration, AABB
Unless otherwise notes, the above is an inclusive list of all sources for the graphs, figures, and
tables, that do not have sources listed beneath them.
41 CHAPTER 5
Results
There are hundreds of reasons a potential donor can be deferred from donating.
Types of deferrals:
A) short-term- allowing the potential donor to reattempt as soon as 24 hours later
B) long-term- lasting a period of several years
C) indefinite- meaning currently they are not eligible to donate but this policy may be
subject to change as technology or understanding changes
D) permanent- which is also referred to as a ‘lifetime ban’
Motivation for deferrals can be separated into two major categories, characteristics that would
put the patient receiving the blood at risk, and risk factors a potential donor might have that
would increase their likelihood of an adverse donor reaction (ADR).
Regulations to Protect the Donor
To avoid ADR, there are several eligibility requirements and recommendations that the
FDA has developed. An analysis of the ARC’s donor data found that for every 1000 presenting
donors, 92.53 are deferred for reasons meant to protect the donor. Of this population, 91.8
individuals will be deferred temporarily, and 0.73 individuals will be deferred indefinitely.52 This
same study conducted over 5 years, found that only 61.2% of donors will return to donate again
after being temporarily deferred for donor safety reasons during their last attempted donation.52
42 1. VITALS: Pulse, Blood Pressure, and Hemoglobin
Pulse
•
Pulse must be between 50 and 100 bpm with few irregular beats to donate, outside that
range will be a 24-hour deferral.
Deferrals based on pulse are enforced to protect the donor's health and reduce the risk
for presyncopal or syncopal reactions. The CFR Title 21 requires all donors to have a “normal”
pulse to be eligible to donate, however they do not assign values to that range.25 ARC defines
“normal” as a pulse between 50 and 100 beats per minute (bpm) with a regular rhythm.53 All
individuals outside of this range will be identified as having an ‘atypical pulse’.
The primary motivation for deferring donors based on pulse is to reduce the likelihood of
donors experiencing a syncopal reaction. A study published in 1961 concluded a high pulse rate
“to be significantly related to subsequent fainting.”54 Very few studies have found such a strong
correlation; in fact, many have concluded that the association is very weak at best. AABB
released a statement in 2009 arguing for the removal of the pulse and blood pressure
regulations.55 When adjusted for confounding factors, a study published in 2008 identified a
weak positive correlation between an elevated pulse (defined as greater than 90 bpm) and any
type of ADR (OR=1.25 CI=1.16-1.34).56 The study also identified a negative correlation between
a slower pulse (defined as less
than 65 bpm) and ADR (OR=0.73
Required Pulse Range For Donors by Number of Countries with Regulation, Figure 6 CI=0.66-0.78).56 These results
50-­‐110 suggest that a lower pulse is
50-­‐100 actually associated with a
reduced risk, and a high pulse is
not the most reliable way to
predict who is at a high risk for
Not Measured Unknown 0 1 2 3 4 5 6 7 Number of Countries with Regulation (n=15, includes US) 43 ADR. The majority of individuals who are deferred for a high or low pulse would have been able
to successfully donate, which is why the current US pulse regulations is classified as strict.
Studies conducted since the 1930’s describing the association between pulse and the
risk of ADR, have varied significantly.55 For this reason, it is not surprising that there is variation
in this policy between countries who have their pulse regulation available to the public. Half of
the countries did not have their regulation on pulse publically available, so with such a small
cohort, it is unclear whether the current distribution, seen in Figure 6, would be maintained with
more data.
Some countries are beginning to transition out of using pulse to assess the eligibility of
donors. The UK completely phased out the measurement of pulse before 2009, and the overall
rate of donors experiencing pre-syncopal ADR was less than 2% in 2010.57 Observing the
outcomes from the UK, Canada has recently announced the removal of their pulse regulation
beginning in May 2015.58 The US regulation does not reflect the most currently available
evidence-based findings, despite AABB’s statement, which advised the FDA to remove the
blood pressure and pulse regulations, because they were not an appropriate risk-measurement
of a person’s likelihood to experience an ADR.55
Blood Pressure
•
Blood pressure must be between 180/100 mmHg and 80/50 mmHg, outside that range
will be a 24-hour deferral.
Blood pressure measurements provide information about an individual’s heart health.
The blood pressure measurement is composed of two parts, the systolic and the diastolic
pressure, written “systolic/diastolic”. The systolic value provides information about pressure in
the arteries as the heart beats. This is used to estimate the strength of the heart contractions.
Diastolic blood pressure measures pressure in the artery between beats. This is done by
constricting the artery and timing how long it takes for the vessel to fill completely with blood
after it is released. The American Heart Association describes a normal blood pressure to be
44 equal to or less than 120/ 80 mmHg and above 85/55 mmHg.59 High blood pressure, also
known as hypertension, is a clinical concern due to the excess force expanding the vessels and
causing damage over time and the increased work of the heart muscle to maintain the pressure.
Varying severities of hypertension lie between 120/80 mmHg and 180/110 mmHg.59
Hypertensive crisis occurs above 180/110 mmHg and requires immediate medical attention, as
it can cause organ damage and other serious complications.59 The current ARC high blood
pressure regulation sets the maximum at 180/100 mmHg, which implies anyone with high blood
pressure who does not need emergency medical attention is eligible to donate.53 A study
observing the ADR rate for individuals with high blood pressure found that donors whose
systolic blood pressure was above 140 mmHg were less likely (OR 0.82, CI 0.74-0.9) to
experience an ADR compared to individuals with a systolic blood pressure between 90 and 65
mmHg.56 Additionally, individuals with a diastolic blood pressure above 85 mmHg were nearly
half as likely (OR 0.62, CI 0.57-0.66) to experience an ADR compared to individuals between 70
and 85 mmHg.56 These findings support the current regulation of having a maximum blood
pressure regulation at the level where it becomes a medical emergency, making the US’s high
blood pressure regulations appropriate.
While high blood pressure can be a major health concern, low blood pressure is the
factor that could potentially have an effect on a donor’s risk for an ADR. Low blood pressure is
usually classified as equal to or below 85/55 mmHg, and is rarely a clinical concern unless an
individual is experiencing symptoms, such as dizziness, fainting, blurred vision, or nausea.59
The majority of these symptoms are also symptoms of an ADR, so it is not unexpected that low
blood pressure can be associated with severe bleeding, like what is experienced during a blood
donation.59 Low blood pressure is also associated with pregnancy, heart or endocrine problems,
septic shock, or anaphylaxis.59 Blood loss exacerbates the possible health concerns for
individuals with low blood pressure.
45 105 Strictest Average Most Lenient 100 g/dL 95 90 minimum regulation to donate blood is
100 97.1 80/50 mmHg.53 This regulation actually
falls below the American Heart
90 85 80 ARC’s blood pressure
Lower Limit for Systolic Blood Pressure, Figure 7 Associations classification for clinically
85 80 relevant low blood pressure.59 When
75 US Regulation International Regulations (n=7) ScientiSic Evidence *Does not include countries with no enforced limit or unmeasured blood pressure 115 g/dL 110 105 100 blood pressure and risk of an ADR, a
Upper Limit for Diastolic Blood Pressure, Figure 8 Most Lenient Average 100 Strictest 110 looking at the relationship between low
study found that individuals whose
diastolic blood pressure is below 70
110 mmHg are 1.38 (CI 1.23-1.54) times
more likely to experience an ADR,
101 100 compared to individuals whose
95 US Regulation International ScientiSic Evidence Regulations (n=7) diastolic blood pressure is between 70
*Does not include countries with no enforced limit or unmeasured blood pressure 65 g/dL 60 55 50 and 85 mmHg.56 This is a slightly
Lower Limit for Diastolic Blood Pressure, Figure 9 50 Strictest Average Most Lenient significant finding, however not a
huge risk factor compared to other
60 55 54 first time donor status. Due to the
50 discrepancy between the lower blood
45 US Regulation International Regulations (n=5) ScientiSic Evidence *Does not include countries with no enforced limit or unmeasured blood pressure risk indicators like age, gender, and
pressure limit and the clinically
relevant cut off for low blood
pressure, the US’s low blood pressure minimum will be labeled as lenient.
Out of the nine countries, including the US, with available data for their systolic blood
pressure upper limit, eight of them had an upper limit of 180 mmHg, and one did not have an
46 enforced upper limit. Ten countries had data available for their systolic blood pressure lower
limit. There was more variation seen in this regulation, with two countries having no lower limit,
the US having a lower limit of 80 mmHg and the remaining countries divided between 90 and
100 mmHg. There was very little variation between the eight countries with information available
on their diastolic blood pressure upper limit. Three out of the nine countries with their diastolic
lower limit regulation posted did not have a lower limit enforced. There is variation for every
value of the measured blood pressure, and overall the US is within the range of the international
collection organizations or the most lenient.
Hemoglobin
•
To donate whole blood, the minimum hemoglobin level for all donors is 12.5 g/dL.
Hemoglobin (Hb) is a critical component of blood and is one of the main determining
factors of screening for healthy donors. To test donor’s Hb levels, collection agencies test a
small amount of blood during the screening process. Normal levels vary by age, race, and
gender, but on average, healthy females are be between 12.0 g/dL and 15.5 g/dL, and healthy
males are between 13.5 g/dL and 17.5 g/dL.60 Despite these significantly different ranges, the
FDA requires all donors, regardless of gender, to have a Hb level above 12.5 g/dL to donate.25
Low Hb is one of the primary reasons for donor deferrals. A study looking at ARC’s donor
populations found that 78.91 individuals in every 1000 presenting donors will be deferred for low
Hb levels.52
Hb levels are an important part of calculating an individual’s allowable blood loss due to
its critical role of shuttling oxygen throughout the body. While Hb and iron levels are related, it is
important to know that the two do not always properly reflect the health of the other. Iron
deficiency does not directly translate into anemia, and vice versa. Individuals can be iron
deficient with or without anemia, and iron deficiency is only one of the many causes of anemia.
Anemia is often a symptom of an underlying condition, like vitamin deficiencies, kidney and liver
disease, hypothyroidism, and some cancers.60
47 Iron depletion (ID) is currently the only well understood, long-term effect of high
frequency blood donations. Iron stores within a donor’s body can be slowly depleted over time, if
there is not adequate time for the body to recovery from the Hb loss.61 ID can lead to long-term
negative health effects for the donors. RD, especially females of childbearing age, are at the
highest risk for iron depletion anemia (IDA). Furthermore, ID is not always reflected on
hemoglobin tests. Hemoglobin levels will remain relatively normal even when donors are
suffering from the beginning stages of IDA. Hemoglobin tests often fail to detect ID, they only
test the amount of hemoglobin currently circulating within the body.
Deferral rates for low hemoglobin in RD do not reflect the high likelihood of ID in frequent
donors. An inverse relationship between frequency of donations and rate of deferral due to low
Hb level was identified.62 The researchers found that 12.3% of the cohort who donated between
one and three times in the past two years were deferred for low Hb.62 This is a noticeably
different rate than the cohort of individuals who donated ten or more times in the past year, of
which only 5.1% were deferred for low Hb.62 The study identified a linear trend, with the rate of
deferral for low Hb decreasing as the amount of blood donations within the two years
increased.62 These same populations were tested for iron stores. The data shows a very
substantial increase in the percentage of individuals with absent iron stores (AIS) within the
cohorts with the highest donation frequency. Donors who have donated between one and three
times in the past two years were 2.5 times more likely to experience AIS compared to
individuals who have never donated blood.62 As the frequency of donations increased, the odds
of AIS in donors increased as well. Compared to non-donors, individuals who donated ten times
or more were 8.6 times more likely to experience AIS.62
There are many ways ID can be addressed in RD, including a longer minimum
frequency between donations, to allow for ample time for the iron store to regenerate through
diet, and a cap on the amount of blood an individual can donate per year. Many countries worry
about the effect on their blood supply if they were to increase the minimum wait between
48 donations, or decrease donation maximum frequencies. Some countries have tried to implement
an iron supplement program to increase iron intake directly after a blood donation to increase
regeneration. However, studies
Minimum Hemoglobin Levels by Gender, Figure 10 Female Minimum Hb 13.5 g/dL have shown that this
Male intervention is not clinically
13.0 g/dL beneficial for non-anemic low
12.5 g/dL iron donors.63
12 g/dL The majority of countries
Unknown 0 1 2 3 4 5 6 7 8 have two different regulations,
Number of Countries with Regulation (n=15, includes US) one for men and one for
14 Minimum Hemoglobin Level for Males, Figure 11 13.5 13.5 g/dL 13 12.5 13 12.5 12 12 Strictest Average Most Lenient 13.5 women. This duality allows for
an appropriate regulation to be
made for both men and women.
When there is one regulation
for both genders, there is no
11.5 value that would avoid
11 US Regulation International Regulations (n=9) ScientiSic Evidence excluding a portion of healthy
women and/ or allow a portion of potentially anemic men to donate. For example, the US
regulation, 12.5 g/dL, defers women between 12.0 g/dL and 12.49 g/dL despite them being
within their normal range. At the same time, this regulation also allows men who’s Hb is
between 12.5 g/dL and 13.5 g/dL to donate, which is below the healthy range for men.
Therefore, the US regulations do not properly reflect the available scientific data, and
instead have chosen to be lenient towards minimum male donor Hb policies and strict
towards minimum female donor Hb policies.
49 There is a significant amount of variation in the Hb regulations between countries. Many
other countries adjust for the difference between genders and have implemented a more
Minimum Hemoglobin Level for Females, Figure 12 12.6 12.5 12.5 12.4 g/dL 12.3 12.2 12 12 11.8 Strictest Average Most Lenient appropriate and applicable policy.
The US regulation falls between
the range of minimums
implemented by the international
12 collection agencies for both
genders.
11.6 US Regulation International Regulations (n=9) ScientiSic Evidence 50 2. AGE: Minimum Age for First Time Donor (FTD), Maximum Age for FTD, and Maximum
Age for Repeat Donor (RD)
Minimum Age
•
The minimum age is state dependent. Some states allow 16-year-olds to donate with
parental consent. All states allow 17-year-olds to donate.
Age has been one of the strongest characteristics tied with ADR next to gender, first
time donor (FTD) status, and estimated blood volume (EBV). The minimum age for donation in
the US varies by state. In most states, teenagers may begin donating on their 16th birthday with
parental consent in the form of a signed waiver. All states allow 17 years old to donate without
parental consent. The majority of 16 and 17 year old donors are FTD, which is associated with
an increased likelihood of experiencing an ADR. FTD are 2.63 times more likely to experience a
significant ADR compared to repeat donor (RD).64 When data was controlled for donor status,
the association between young age and ADR was still present.64 Not only was this relationship
evident, but age was found to have an even stronger association with ADR. Individuals under 18
are 3.05 times more likely to
Reaction Rate (per 1000 donations) for First Time and Repeat Donors B y Age, Figure 13 experience an ADR
compared to donors over 20
years old.64 Additionally, as
shown in Figure 13, while
FTD are more likely to
experience an ADR
compared to RD in the same
Source: T. Wiltbank et. al. Transfusion. 2008.
age bracket, younger RD are
still at a higher risk for experiencing an ADR compared to older FTD.56 Once again, showing a
stronger relationship between age and the likelihood of experiencing an ADR compared to FTD
status.
51 Donors under 18 make up a relatively small portion of the donor population, accounting
for 700,000 donors per year, or 8.09% of the total annual donor population.65 Individuals ages
16 to 19 account for approximately 40% of FTD, making this a more important population to the
future of the blood supply, rather than the current supply due to their disproportionate
contribution to the incoming population.41 On average, 32% of all FTD experience an ADR.
Additionally, FTD are 25% less likely to return to donate if they experience an ADR, compared
to FTD who did not experience an ADR. Each year, 280,000 FTD under 18 will experience an
ADR. Only 30% of this population will return to donate again, accounting for a loss of nearly
200,000 donors annually. The increased likelihood of FTD between the ages 16 to 18
experiencing an ADR ends up having a significant and sustainable negative impact on the future
population of blood donors, making the US policy lenient in comparison to scientific data.
There are only two countries
Minimum Age for First Time Donors, Figure 14 that allow individuals under 17 to
18.5 18 Age (Years) 18 17.5 17.5 17 16.5 16 16 16 donate 400 mL or more of whole
Strictest Average Most Lenient 18 15.5 US Regulation International ScientiSic Evidence Regulations (n=14) blood, the US and Australia. The
partial exception to this is Japan,
where 16 year old males may begin
donating 200 mL, however, they
may not begin donating 400 mL until
after their 17th birthday. The average
for the minimum required age for FTD in the international study population was 17.5, with 9 out
of the 15 countries’ first donation occurring after an individual’s 18th birthday.
52 Maximum Age
•
There is currently no maximum age for donation, as long as, the donor is in good health
and meets all other requirements.
In the US, there is currently no mandated maximum age to cease donations. Collection
agencies state, as long as, a donor is in good health and meets all other eligibility requirements,
age should not be a reason for deferral. The aging of the donor population has been a concern
for the US as the baby boomer population moves towards their 60’s and 70’s. A study looking at
ARC donor demographics over 9 years found troubling trends, noticing an annual 1.4% increase
in RD over 50 and an annual 1.3% decrease in donors ages 25 to 49.35 As the donor population
continues to age, the implications of a maximum age limit would have damaging effects of the
future national blood supply.
Many studies have looked at the relationship between ADR and age.66,35,67 A study
conducted in Germany observed the effects of removing an upper age limit. They found RD
over the age of 69 were approximately 6 times less likely to experience ADR compared to RD
between the ages of 18 and 30.68 This reiterated the inverse relationship between age and
likelihood of experiencing an ADR found in many other studies. However, the study also found
that elders who did experience ADR were more likely to experience severe ADR and need at
least 30 minutes until they felt fully recovered.68 This is compared to donors under 68 who were
more likely to experience a moderate reaction and usually recovered in under 15 minutes.68
While the severity of reactions is a concern, the extremely decreased likelihood of an elderly
donor experiencing an ADR greatly reduces the population of individuals who will experience
these severe complications.
In the process of changing their own policies, a Canadian study used data collected from
the US to observe the effects of removing an upper age limit. In addition to the lack of ADR
associated with older age, the publication also points to the discrepancies in their own policies
regulating maximum age limits between “jurisdictions” in Canada as further evidence “that there
53 is no absolute scientific rationale underlying the upper age limit for donation.”67 While there is
wide variation between countries’ maximum age limit for donations, the US policy
appropriately reflects the current scientific information available. Additionally, the fact that
other countries are changing their upper age limit to match the US’s policy further reflects the
appropriateness of the policy.
There is a large amount of
Maximum Age for First Time Donors, Figure 15 72 Most Lenient Age (Years) 70 68 66 64 research is needed in this field to
63.3 Strictest 60 58 54 concerning age. This suggests further
Average 62 56 variation found in all regulations
71 none US Regulation understand how to reduce the impact
60 of ADR on the younger donor
none International Regulations (n=14) ScientiSic Evidence population to feel comfortable
Maximum Age for Repeat Donors, Figure 16 Most Lenient Age (Years) 80 75 70 65 55 81 Average 69.2 Strictest 60 60 none US Regulation continuing to donate into their old
age.
85 50 population, and how to support the RD
none International Regulations (n=13) ScientiSic Evidence 54 3. BLOOD COLLECTION: Estimated Blood Volume,
Volume and Frequency of Donation
Estimated Blood Volume (EBV)
•
The minimum weight for all donors is 110 lbs.
The FDA requires all donors to weigh at least 110 lbs. (50 kg) to make sure they have a
large enough volume of blood to withstand the loss caused by the donation. US regulations
restrict blood collection to 10.5 mL collected per kg of the donor’s weight. This allows for a
maximum of 525 mL to be legally removed from an individual who weighs 110 lbs. While this
greatly varies between individuals, the general understanding is no more than 15% of a
person’s total blood volume, classifying the blood loss as “minor,” can be lost without an
individual experiencing symptoms of massive blood loss.69 Estimated blood volume (EBV) is
calculated using a donor’s height and weight. The average volume of blood for an adult is
approximately 60 mL per kg.
Studies have identified a very strong inverse relationship between EBV and ADR. A
study analyzing over 400,000 donations identified characteristics that were most closely
associated with ADR. They found that 3.49% of donors whose EBV was less than 3,500 mL
experienced some type of ADR.56 As the EBV increased, the percentage of the cohort
experiencing an ADR, with 2.35% of individuals with an EBV between 3,500 mL and 4,000 mL,
1.44% of individuals with an EBV between 4,000 mL and 4,775 mL, and 0.80% of individuals
with an EBV of more than 4,775 mL experiencing an ADR.56 Another study with a total
population of nearly 600,000 concluded that individuals with EBV of 3,500 mL were
approximately 2.5 times more likely to experience an ADR compared to individuals with EBV
above 5,000 mL.70 Results from observational studies strongly suggests low weight is closely
related to an increased likelihood of ADR, making the US policy lenient in comparison to
scientific data.
High school drives have been notorious for having a high rate of ADR, the majority seen
in smaller female students. To address this concern, ARC developed a sliding scale for height
55 and weight requirements, which applies to all high school students until their 18th birthday. The
weight requirements affect males under 5’ and females under 5’6”. The sliding scale uses an
inverse relationship between height and weight to control for the minimum EBV individuals need
to donate blood. This is a policy implemented by ARC and is not something that was suggested
by the FDA, however many other collection organizations are beginning to implement similar
policies after seeing the reduction in ADR.
Internationally, only two countries have chosen to implement a sliding scale for their
younger donors that is similar to ARCs regulation. Canada’s scale applies to all individuals
under 23 years old, and the UK’s scale applies to female donors under 20. Other then those
scales effecting a specific minority donor population, there was no variation for the minimum
amount of weight the donor must be to donate 400 mL or more of blood between the 15
countries in the study. All countries required individuals to weight at least 50 kg. Japan was the
only exception, collection agencies allow donors to choose between two volumes to donate.
In Asia the average body weight is 57.7 kg, which is significantly lower than Europe’s
average body weight of 70.8 kg, North America’s average body weight of 80.7 kg, and
Oceania’s average body weight of 74.1 kg.71 To combat this limitation, many Asian countries,
Japan included, allow individuals to donate either 200 mL or 400 mL. The weight, age, and Hb
requirements are lower for the 200 mL donations compared to the 400 mL donation, leading to a
larger population of eligible individuals. Other countries included in this study do not experience
this same pressure, and therefore have not been forced to create this two volume system.
Overall, the policy that applied to the largest donor population in every country was a minimum
weight of 50 kg.
56 Volume and Frequency of Donation
• In the past 8 weeks have you donated blood, platelets or plasma?
• In the past 16 weeks have you donated a double unit of red cells using an apheresis
machine?
The replacement of the donated blood varies by component, but the overall volume of
blood is quickly equalized within hours by the flow of extravascular fluid into the circulating blood
from surrounding tissue.b This increase in extravascular fluid results in the restoration of the lost
plasma. RBC take longer to regenerate, several weeks before the loss is completely
compensated for. The cell formation rate for a normal adult is about 200 billion RBC per day, 10
billion white blood cells per day, and 400 billion platelets per day. However, this varies widely by
individual. RBC concentration is closely monitored and maintained by the body. For those who
have recently experienced a loss of RBC, the cell formation, or erythropoietic activity in the bone
marrow, will increase until the body returns to homeostasis. Approximately 1% of an individual’s
RBC are created each day, while old RBC are simultaneously removed. For an average adult in
homeostasis, erythropoietic activity produces a little less than one pint of RBC every week.
However, if the body were to experience a large blood loss, erythropoietic activity can be
increased 8 fold. This is not a sustainable formation speed, so prolonged periods of RBC
reduction leads to anemia over time due to the depletion of iron stores. Platelet production can
also be physiologically controlled by the body if it experiences a sudden drop in concentration,
however it is not as closely maintained as RBC.
Some long-term effects of repeat blood donations have been suggested through
experimental and observational studies. A causal relationship between frequent donations and
decreased iron has been well documented, and is especially present in women of childbearing
ages. Multiple studies have also identified a higher prevalence of restless leg syndrome in
repeat blood donors.72 This trend is primarily seen in men, and remains relatively unexplained.
b Unless otherwise indicated, data for this sections is based on Schwartz, RS and Conley, CL. “Blood,” 151
Encyclopedia Britannica, 2014. 57 Most hypothesis of all long-term adverse effects stem from the reduction of iron stores over
time. Therefore, implementing policies that reduce the strain put on donor’s iron stores would
benefit the donor in the long run. Collection agencies in the US usually collect around 500 mL
including the sample tubes used for screening and is among the group of countries that allow
the largest volume of blood to be collected. The amount of blood that is removed from a person
is significantly more than what scientific
evidence suggests should be the upper
510 500 limit, making the US policy on volume
490 of donation lenient. Additionally, the
mL 470 prevalence of IDA in American donor
450 suggests the minimum amount of days
430 between donations is not enough to
410 maintain the problem iron stores,
consequently making the US
frequency policy to be too lenient.
Scientific evidence suggests no
Maximum Amout of Whole Blood Collected During a Donation, Figure 17 Most Lenient Average Strictest 500 478.75 450 400 390 US Regulation International * ScientiSic Evidence Regulations (n=12) * Does not include Japan's smaller volume of 200 mL, which has different donor requirements than their standard 400 mL donation volume more than 15% of blood should be removed from the body during a blood donation and the
average volume of blood for an adult is 60 mL per kg of body weight.69 The ARC chooses to
collect only one volume from their donors. This differs from many other countries, which have a
range of volumes collected based on a donors EBV. For example, Italy will collect 450 +/- 10%
depending on the donor’s height and weight. Due to ARC’s limitation, the volume must
accommodate their lightest allowed donor, 110 lbs. Using this information, ARC should be
collecting no more than 450 mL of blood, including the samples for screening.c The scientifically
c 110 lbs= 50 kg x 60 mL/kg[average blood volume per kg in an adult]= 3,000 mL of blood in a 110 lb adult
3,000 x 0.15 [suggested maximum percent of blood that is safely removed from a donor]= 450 mL of
blood collected
58 suggested 15% of blood volume and the US’s law of 10.5 mL per kg do not coincide, leading to
the discrepancy between the evidence-based volume and the actual volume collected.
Maximum Frequency of Blood Donations for Males Over 18 Donating 400 mL or More, Figure 18 120 Frequency (Days) 100 80 60 56 40 Strictest Average Most Lenient 112 67.5 56 20 0 US Regulation International Regulations (n=12) ScientiSic Evidence Maximum Frequency of Blood Donations for Females Over 18 Donating 400 mL or More, Figure 19 120 Frequency (Days) 100 80 60 56 40 Strictest Average Most Lenient 112 75.5 56 20 0 US Regulation International Regulations (n=12) ScientiSic Evidence 59 4. PREGNANCY
•
Female donors: in the past 6 weeks, have you been pregnant or are you pregnant now?
Very little research has been conducted analyzing the risk of blood donations during
pregnancy, because any increased risk to the mother or fetus would not be advised. Therefore,
the true safety has yet to be established using evidence-based findings. One small-scale study
conducted in the late 1980’s observed 48 women in their third trimester who wished to donate
blood.73 One major concern for blood loss during pregnancy is postpartum anemia and the need
for a transfusion after birth. The incidence of postpartum transfusions was used as one metric to
quantify the risk of donating blood while pregnant. They also monitored the mother and fetus’s
heart and neurological patterns during the collection process for any abnormalities. Before the
donations, the team identified 17 women who they believed were at a higher risk for needing a
transfusion after childbirth.73 Out of the cohort of women, nine were ineligible to donate, and the
remaining 31 women each donated between one and three times during the duration of their
pregnancy, for a total of 61 donations.73 Out of the 61 donations, there was one ADR resulting in
a brief loss of consciousness, and three donors ended up needing postpartum transfusions.73
Two out of the three women needing the treatment were identified as high risk before the
donations.73 The donation itself was safe for both the mother and fetus, however, the long-term
effects of donating blood while pregnant could end up having adverse effects on the mother’s
health resulting in the need for postpartum transfusions.
The large variation for countries’ deferral periods after childbirth is not unexpected due to
the lack of scientific evidence. Some possible justifications for a deferral period is to give the
mother’s body time to recover from the stresses put on the body during childbirth. Additionally,
especially in the case of caesarian sections, the women often experience a moderate amount of
blood loss, which would also support the need for a deferral period. While the US does not have
a regulation surrounding breastfeeding, many other countries require women to wait to donate
blood until after her child has been weaned. The validation for this regulation is because a
60 mother’s milk supply is based on her hydration. Donating blood removes a significant amount of
fluid from the system, putting a woman’s
milk supply in jeopardy. Due to the lack of
Deferral Period After Childbirth, Figure 20 14 12 regulation, the level of appropriateness
of the pregnancy deferral policy is
10 Months evidence to dictate an evidence-based
Strictest Average Most Lenient 8 6 4 unknown, however the limited data
2 suggests it is lenient.
0 12 7.3 6 1.5 US Regulation unknown International Regulations (n=14) ScientiSic Evidence When evidence is lacking, the level
of precaution a country takes in terms of their donor’s health becomes evident. The US has an
extremely lenient policy compared to the other countries included in the study, falling
significantly below the second most lenient policy and nearly 6 months below the average of
international regulations, as seen in Figure 20. The leniency can also be seen surrounding
regulations for deferrals after miscarriages and abortions, and policies related to breastfeeding,
found in the Appendix.
61 5. CHRONIC DISEASES: Cancer, Heart and Lung Health Issues, and Diabetes
Cancer
• Have you ever had any type of cancer, including leukemia?
Due to the minimal research done in this area, very little is known about the risks for the
donor or the patient receiving the blood of cancer survivors donating blood. Multiple studies
have concluded that donating blood is not a risk factor that would cause cancer, but few have
looked as the possibility of cancer cells transferring from a donor who has or had cancer to a
patient, or the health effects on the cancer survivor. Many cancer survivors feel compelled to
donate blood once they have fully recovered because so many of their treatments often
contained human blood components. In the US, individuals who have had malignant cancers
unrelated to the bones or blood may donate after one symptom free year following a complete
recovery from the cancer. Non-malignant cancers most likely will not cause a deferral after
complete recovery, but some exceptions apply. Cancers, which effect the blood, such as
leukemia, can potentially damage the individual’s blood production capacity long after complete
remission. Additionally, some hypothesize that cancer cells within the blood could be
transmitted to a transfusion patient. While there has never been a reported case of this
occurring, the most likely situation it would occur in would be a cancer of the blood. Cancers of
the bone also lead to a lifetime deferral, because they can cause long-term damage to the bone
marrow, where blood cells are produced. This could potentially reduce a donor’s ability to
replace the cells lost from the donation.
Very little research is available on the outcome of cancer survivors donating blood.
However, a retrospective cohort study observed over 12,000 transfusion recipients who were
exposed to blood from “precancerous donors.”74 The entire study population contained over
300,000 transfusion patients, and the researchers concluded there was no evidence to suggest
any additional cancer risk for the patients who were exposed to preclinical cancer via a blood
transfusion.74 The study assumed that individuals who were diagnosed with cancer following a
62 blood donation would provide the necessary exposure to be able to observe a potential negative
outcome. These results suggest that cancer cells within a blood transfusion do not increase the
risk for the patient receiving the blood. For this reason, the regulation should be viewed as a
policy that is put in place to protect the donor, rather than the recipient of the donated blood.
The lack of scientific data available means this policy cannot be labeled at lenient, strict
or appropriate, therefore its relationship to evidence-based data is unknown. However,
from what is known about the physiological aspects of cancer, a year is not an adequate
amount of time to determine complete health, suggesting this policy is lenient.
While many countries allow individuals to donate blood after complete recovery from a
non-malignant caner, the US is one of only two countries which allow donations from donors
who have recovered from a malignant cancer not effecting the blood or bones. The other
country that allows individuals who have had malignant cancers is Australia. However,
Australia’s deferral period is significantly longer than the US deferral period, 5 years versus 12
months, respectively. In this situation, the US is the most lenient country.
There is not a consensus on the reasoning behind regulations for individuals who have
recovered from cancer. The UK explains their lifetime ban is to protect the patients receiving the
blood, because the policy is based on “a theoretical risk that a cancer cell could be passed on in
the blood.”75 However, they also note that they have yet to find “evidence to prove that this is a
possibility.”75 Australia has a different motivation for their regulations surrounding donors who
have recovered from cancer. They state the deferral is “to protect the donor’s health by ensuring
as far as possible that the cancer is gone and will not recur.”76 Australia’s permanent ban on
individuals who have had cancers effecting the blood or bones is also meant to be for the
protection of the donor.76 All other countries included in this comparison have a lifetime ban for
any type of malignant cancers.
63 Heart and Lung Health Issues
•
Have you ever had any problems with your heart or lungs?
Diseases that effect the heart and lungs range drastically in severity, symptoms, and
circulatory resilience. Deferrals based on the health of an individual’s circulatory system are
done to protect the donor’s health and make sure they can withstand the blood volume loss,
they are able to replace the missing cells adequately, and they do not risk experiencing a
serious adverse health event from the body’s shock of the blood removal. The questions many
collection agencies choose to ask are broad to assess the donor’s overall circulatory system
health. Each collection site has different stipulations surrounding the deferral of individuals who
have experienced a stroke or heart attack, or have other related conditions, like heart disease,
heart failure, COPD, and chest pain. For most conditions, including heart attacks, chest pain,
angina, a change in medication meant to treat symptoms from a heart related condition, or heart
disease, ARC defers donors for 6 symptom-free months following their last episode.53 In
general, chronic diseases do not effect an individual’s donation eligibility, as long as, they pose
no risk to the patient receiving the blood, they are otherwise in general good health, and they
meet all the other necessary requirements to donate blood.
The connection between the risk for a heart attack and blood donation has been
disputed for many years. Researchers who believe the act of donating blood could trigger
amyocardial ischemic event put conservative risk estimates at slightly less than 1 in one million
blood donations.77 This risk rate is slightly above the baseline risk for individuals between 45
and 70 years old, 0.3 per one million donations, but half of the increased risk associated with
sexual activity for this population, which would be equal to is 2 in one donations.77 Other studies
looking at the relationship between blood collection and heart attacks have concluded there is
no associated or increased risk for healthy donors.78 Researcher’s analysis of studies which
found a positive association when collecting data on this relationship believe the observed risk
of cardiac events for some studies only occurred in donors who had preexisting heart
64 conditions, making a deferral of this population a possibility for reducing the potential risk.79 The
existence of this finding suggests the US policy for heart and lung issues is lenient,
however, due to the lack of data, the true relationship between the regulation and
evidence- based data is unknown.
All countries, excluding the US and Canada, have instituted lifetime bans for any
individual who has experienced a heart attack, stroke, any type of heart disease, or heart failure.
In some countries, chest pain, arrhythmias, pacemakers, or any type of cardiac surgeries also
lead to a lifetime deferral. Canada allows “asymptomatic” individuals to donate blood, but they
have a lifetime ban for any individual with coronary artery disease. The Canadian Blood
Services explain their method of conducting health histories is done to assess a donor’s
individual level of heath to decide if they are eligible to donate. In many cases, asymptomatic
individuals will be eligible, however, site specific regulations differ in terms of length of time an
individual must be symptom-free, the clinically relevant symptoms which would cause a deferral,
and the deferral period for ineligible donors. The US has a much more generalized policy of a 6
month symptom-free period of time before individuals with circulatory disorders may donate.
Canada and the US are the only sources of variation for the comparison of policies effecting
individuals with circulatory disorders. The US’s nonspecific 6 month deferral period and
Canada’s individualized deferral periods are the most lenient out of all of the countries included
in this study.
Diabetes
There are three types of diabetes, Type 1 diabetes mellitus (Type 1), Type 2 diabetes
mellitus (Type 2), and gestational diabetes. However, only the first two would be relevant to
discuss in terms of eligibility for donating blood, because the last is a temporary condition
associated with pregnancy. Type 1 diabetes, also known as juvenile diabetes, is associated with
a body’s inability to produce enough insulin due to autoimmune destructive mechanisms in the
pancreas. The cause of Type 1 diabetes is unknown, but individuals can keep their condition
65 well managed through injections of artificial insulin. Type 2 diabetes, also known as adult-onset
diabetes, is characterized by the gradual development of insulin resistance, and represents 90%
to 95% of all diabetes mellitus cases.80 Type 2 diabetes is a metabolic disorder and is thought to
generally be caused by obesity, although there are some genetic factors that can predispose an
individual to developing it. Treatment for Type 2 usually consists of diet and exercise to manage
the high glucose levels, however, if the condition progresses, some individuals develop the
need for oral medications or insulin.
Similar to the previous two sections discussing chronic diseases, the relationship
between diabetes and blood donations is relatively unknown. The purpose of some countries
deferring individuals with diabetes is to protect them from ADR caused by changes in an
individual’s glucose levels or insulin sensitivity. Studies have been conducted observing the
relationship between insulin sensitivity and iron stores in blood donors. The results concluded
that frequent blood donors had a higher level of insulin sensitively and a lower level of iron
stores compared to non-donors.81 This study did not use diabetic individuals in their study
population. Due to the lack of data available for diabetic blood donors, the relationship between
evidence-based data and the US diabetic donor regulation is unknown. However, the fact
that a relationship between insulin sensitivity and blood donation exists in non-diabetic donors,
suggests a similar relationship might exist for diabetics. This relationship would suggest that
Type 1 diabetics, who have reduced control over their insulin levels, might be put at risk when
donating blood. So while this policy is labeled unknown, small amounts of data suggest the
policy is lenient.
A systematic review of the safety of Type 2 diabetics donating blood was conducted in
the UK in hopes of providing relevant data to apply to their regulations surrounding the eligibility
of diabetics. The researchers discussed their disappointment in the lack of research surrounding
this topic. They concluded that none of the studies they identified suggested Type 2 diabetics
would have any increased risk for ADR.82 Some studies have even concluded donating blood
66 might have preventative measures against Type 2 for men who have normal to high iron
levels.83 Results showed frequent donors’ insulin and glucose metabolisms functioned at a
higher level compared to non-donors.
US and Australia are currently the only two countries that allow Type 1 diabetics to
donate blood. All other countries may allow Type 2 diabetics to donate depending on their
history with insulin dependence. In most cases, diabetic individuals may donate as long as their
condition is well controlled using only diet and/ or oral medications. Similar to cancer, Australia
and the US are the major outliers, and extremely lenient compared to the other countries
included in the study.
67 Regulations to Protect the Patient
6. Exposure: Tropical Infections (Malaria, Chagas Disease, Babesiosis, West Nile Virus,
Creutzfeldt-Jakob’s Disease, and Variant Creutzfeldt-Jakob’s Disease)
Malaria Infection and Travel to Malaria Endemic Areas
• In the past three years have you been outside the United States or Canada?
• Have you ever had malaria?
Although malaria was eliminated from the US in the beginning of the 1950’s, it still
represents a huge international health burden, accounting for 150 million infections resulting in
up to 2 million deaths annually.84,85 Malaria is an infectious disease caused by parasites that
infects mosquitos who then act as a vector infecting people whose blood they subsequently
feed on.86 The infection begins in the liver and then infects RBC as the disease progresses,
making it transmittable through blood-to-blood contact. There are multiple strains of malaria
which are associated with different endemic regions, latent periods, and severity.87
Non-immune individuals are those who grew up in non malaria-endemic (NME) areas.
They were never exposed to the infection, and therefore, never developed any kind of
resistance. Due to this susceptibility, they are more likely to develop a more severe case of
malaria. In non-immune individuals, severe malaria develops anywhere between 7 and 15 days
after infection, and can kill the individual in as little as 24 hours without medical treatment.87
Less severe forms of malaria can be difficult to diagnose in non-immune individuals because
symptoms like elevated temperature, perspiration, and shivering are often associated the flu or
other common viruses. Non-immune individuals will contract an acute version of the disease,
which will become identifiable well within a year, depending on the strain. At that time more
clinically relevant symptoms appear, like enlargement of the liver and spleen and mild
jaundice.86 Diagnoses are made by observing the parasite in RBC.86
Human immunity will develop in individuals who have been exposed to the parasite by
residence in malaria-endemic (ME) areas. This limited immunity reduces the risk of the more
severe form of the illness and decreases the likelihood of death, however is does not completely
68 protect the individual.87 Immune individuals have still contracted the disease, and can still
transmit the disease through blood-to-blood contact, but the multiple low grade activations of the
disease makes it more likely to remain latent for a longer period of time, making diagnosis
especially difficult.
The CDC publishes the status of all ME countries for reference (see Appendix), with
information about the risk for US travelers, the local malaria species, the recommended
prevention method, any common drug resistant strains, and the individual cities and towns in
each country with the highest risk for infection.88 This information is used by blood collection
agencies to define travel regulations to reduce the risk of spreading malaria to patients. The
travel and residence regulations for malaria apply to anyone who has traveled or resided in a
ME area for more than 24 hours. The FDA defines residence in a ME country as “a continuous
stay of longer than 5 years in a country or countries having any malaria-endemic area.”89 A
potential donor who has resided in a ME country should be deferred for three consecutive
symptom-free (CSF) years after moving to a NME country.89 If such an individual returns to a
ME area before the three-year period is over, the deferral period resets, and they must wait
another three CSF years before being eligible to donate.89 However, if such an individual fulfills
the three CSF year deferral period before traveling to a ME area, they should only be deferred
for one CSF year following their return.89 This is only the case if the travel was less than 5
years. If the trip was longer than 5 years, it would be considered residence, and the deferral
period would be reset to three CSF years. The FDA suggests that individuals who have
traveled to a ME area should be deferred for one CSF year, regardless of whether they took
preventive chemoprophylaxis drug.89 The FDA suggests that an individual who has previously
contracted malaria and undergone treatment should be deferred from donating blood for three
CSF years after complete recovery.89 The deferral periods reflect the maximum amount of time
the disease might remain undiagnosed and untreated within an individual for the strain with the
69 longest latent period. The FDA does not specify between different area’s most prevalent strain
and their average latent period.
A study conducted over 5 years found, on average, less than 9.6% of first time
presenting donors will return to try to donate again if temporarily deferred specifically for malaria
risks.52 This is compared to 63% of repeat donors who returned after being temporarily deferred
for malaria risk.52 Using these percentages, the study predicts that in 5 years, ARC lost over
130,000 donors due to the low return rates after deferrals for malaria exposure.52 A loss of
130,000 donors over 5 years is associated with a loss of over 221,000 donations, and up to
663,000 blood products, the following year. This significant loss of completely eligible donors
due to a temporary deferral is a common theme when looking at trends in donor behavior. The
results enforce the need for as few unnecessary deferrals as possible, to not only protect the
current blood supply, but also the future blood supply.
In 2006, a study collected data from 6 nationally dispersed blood collection centers and
estimated that for every 1000 presenting donors, 10.2 donors were deferred for malaria
exposure due to travel.90,91 Of the 2,108 deferred donors recorded, the majority were exposed in
“low risk” areas like Mexico (41%), the Caribbean (13%), and Central America (22%).90 The
remaining donors were deferred due to travel to “high risk” areas like Africa and Oceania.90
Another study analyzing the same data estimates that over 60,000 donors are deferred annually
for travel to ME areas in Mexico, while travel to ME areas in Africa is only responsible for 5,500
deferrals a year.91 In 2005, 444,936 Americans traveled to ME areas in Africa.91 Of this
population, 611 travelers returned with malaria. In contrast, 4 million Americans traveled to ME
areas in Mexico, yet only 5 people returned from Mexico with malaria.91 Additionally, only 0.03 in
10 million Americans who contracted malaria in Mexico remained asymptomatic after 90 days,
compared 0.9 in 10 million Americans who contracted malaria in Africa who remained
asymptomatic after 1 year.91 The difference in disease manifestations is due to the different
strains found in the area. These results suggest travel to ME areas in Africa is associated with
70 “1100-fold higher risk for malaria” compared to the ME parts of Mexico.90,91 The study also found
if deferral lengths due to travel to ME areas were reduced from 12 months to 3 months, an
additional 56,000 donations would be added to the blood supply annually, with only one
additional malaria contaminated unit collected every 57 years.91 This is comparable to the
possibility of infectious units entering the blood supply from donors who have returned from ME
areas in Africa with our current regulations.
Between 1963 and 2011, 97 cases of transfusion-transmitted malaria were reported.85
An estimated two thirds of the cases were traced back to donors answering dishonestly, and
would have been prevented if the guidelines had been followed.85 Therefore, these
transmissions would still be present regardless of what policies were in place. Only one third, or
0.65 transfusion transmitted malaria cases per year, might have been addressed with a change
in policies.85 The change in policy suggested by the study would increase this figure to 0.667
cases of transfusion transmitted malaria per year, or 2 cases per year if the infections caused by
dishonest answers are
Deferral After Travel to a Malaria Endemic Area, Figure 21 d
included. This new rate of, 0.06
40 35 malaria infections per one
comparable risk of all other
transfusion transmitted
infections of concern, like HIV,
HBV, and HCV.e The absence
Months 30 million transfusions results in a
25 20 15 10 12 5 0 US Regulation Strictest Average Most Lenient 36 9.2 4 African and Oceania Central and South America International Regulations (n=14) 12 3 ScientiSic Evidence d
1/ 57= 0.017 [increase in malaria infected donations per year if the deferral period was shortened from 12 months to
3 months for Mexico alone] + 0.65 [the number of annual malaria infections due to gaps left by the current policies]=
0.667 [cases of transfusion transmitted malaria if the deferral period was shortened from 12 months to 3 months for
Mexico alone]
e
(2 [estimated number of transfusion transmitted cases of malaria if the deferral rate for travel to Mexico was
shortened from 12 months to 3 months]/ 30,000,000 [number of blood products transfused every year]) X 1,000,000=
0.06: 1,000,000 [rate of transfusion transmitted malaria cases if the deferral rate for travel to Mexico was shortened
from 12 months to 3 months] 71 of regulations that properly reflect the relative risk of transfusion transmitted malaria
leads this specific policy to be categorized strict.
There was a significant level of variation surrounding the restrictions for travel to a ME
area between the international countries included in the study. The deferral period for 8 out of
the 16 countries included in the study is 6 CSF months. Two countries, France and Australia
have more lenient regulations, requiring only 4 CSF months. In the case of malaria based travel
deferrals, Italy is the major outlier, with a much stricter deferral period of 3 CSF years. The
average deferral regulation of the international countries included in the study is 9.2 CSF
months following the individuals return. The US’s regulation is above this average with their 12
CSF month deferral period. Scientific evidence is not well reflected in any of the country’s policy,
however it may identify closest with the 6 month deferral found the majority of the study
population.
Chagas Disease and Babesiosis
•
•
Have you ever had Chagas disease?
Have you ever had Babesiosis?
Chagas disease, also known as American trypanosomiasis, is a disease caused by
Trypanosoma cruzi, a parasite carried by the triatomine bug.92 While endemic to the Americas,
Chagas disease has spread to other continents and effects between 7 and 8 million people
internationally.92 The majority of infections take place is Latin America, where they refer to the
Chagas vector as the “kissing bug.”92 Chagas disease initially presents with little, to no,
noticeable symptoms, and begins approximately two months after infection.92 During this time, a
large quantity of parasites circulate in the blood, making it easily transmissible via blood
transfusion.92 One indication of infection is a “purplish swelling” or lesion around a single eye lid,
however this occurs in less than half of all infections, and only in cases where the infection was
caused by excrement entering an individual’s eye.93,92 During the second, and chronic phase of
Chagas disease, the parasites accumulate in the heart and digestive muscle.92 The majority of
72 individuals are asymptomatic during this time but some will suffer from heart or digestive
disorders.92 After several years, an infected individual will suddenly die of heart related
complications due to the parasites’ degradation of the heart muscles.92 Chagas disease can be
easily treated with benznidazole and nifurtimox.92 These drugs are nearly 100% effective if
given right after infection during the acute phase.92 However, the effectiveness of the treatment
decreases as the disease progresses, and the treatment itself is usually disruptive to an
individual’s life, with 40% of individuals reporting adverse side effects over the two month
treatment course.92 Because Chagas disease is endemic the North America, the US currently
does not have any deferrals based on exposure and addresses this health concern by asking
donors if they have ever been infected with Chagas disease. Anyone who has ever been
infected is deferred from giving blood for life, regardless of treatment or time since recovery.
The same policy is used for a very similar parasitic infectious disease, Babesiosis.
Babesiosis is also a parasitic disease carried by a vector found in the US, and shares
many other of the same traits as Chagas disease. The parasite, Babesia microti, is spread by
the deer tick, which is commonly found during the warmer months in the Northeast and upper
Midwest.94 Babesiosis parasites attack and destroy the RBC of an individual, causing hemolytic
anemia, which can lead to jaundice-like symptoms.94 Other common complications include low
blood pressure, hemolysis, low platelet count, and vital organ irregularities.94 In the majority of
Chagas disease and Babesiosis cases, primary symptoms are usually mild, and can include
fever, headache, muscle pain, and other non descript symptoms, making diagnosis difficult.92,94
Babesiosis infections vary in severity, but can be life threating to immunocompromised
individuals, like the elderly, individuals without a spleen, or individuals with serious health
conditions like cancer, HIV/AIDS, and liver disease.94 Treatment is available through a
combination of anti-parasitic medications, however flare-ups have been observed, which
suggests that even when asymptomatic, the individuals still carries the parasite regardless of
treatment.94
73 Both the deer tick and the triatomine bug have been reported in about half of the US,
specifically in the southern and eastern parts of the country.93,95 Because there is no vaccine for
Chagas disease or Babesiosis, the best prevention method is vector control via insecticide
spraying and avoidance of high risk areas.93 Other than through contact with the blood-sucking
vector’s, Chagas disease and Babesiosis can be passed through blood transfusions, organ
transplants, and from mother to child during birth.92,94 The presence of the vectors and parasites
in the US has led to the implementation of screening for Chagas disease on all blood donations
to reduce any possible transmission.93 However, there is currently no approved blood test to
screen for Babesiosis.94 The lack of a sensitive and specific blood screen for Babesiosis has
become increasingly concerning. ARC considers themselves “lucky” that an adequate and
affordable screen for Chagas disease was developed so soon after it was flagged as a public
health concern.96 The CDC estimates one in every 27,500 units of blood tests positive for
Chagas disease.97 The quick implementation of the Chagas disease screen is awarded with
curbing a predicted large spread of the infection throughout the US. Despite researchers’ and
medical technology developers’ best efforts, an equally fitting screen has not be developed for
Babesiosis.
In some ways Babesiosis is currently the most uncontrollable infectious threat to the US
blood supply. There has been a huge push to develop a blood test to protect patients receiving
blood. In 2012, National Institutes of Health awarded the Boston based company Immunetics a
$3.7 million contract to develop a blood test.98 They published their research in 2014 and
concluded that, while the tests they were developing are showing positive results, there are
many limitations to the current model, including questionable cost-effectiveness, and the “grey
area” within the testing results leading to subjective diagnoses.99 While strides are being made,
the lack of screen currently in place is putting patients at risk, posing a major public health
problem.
74 Even while effective treatments for Chagas disease and Babesiosis exist, they may not
completely clear an individual’s system from the parasites, maintaining the risk of transmission if
the individual were to donate blood. The current US regulation indefinitely defers any individual
who has been infected with Chagas or Babesiosis from donating blood.53 These regulations
properly reflects the transmission risks of Chagas disease and Babesiosis, and therefore
are appropriate regulations.
The majority of countries also have a lifetime ban on anyone who was ever infected with
Chagas disease or Babesiosis. Additionally, a travel deferral was seen in many of the countries.
In most cases the travel deferral was grouped together with the deferral for West Nile Virus and
lasted 4 CSF weeks after return from an endemic area like the US, Canada, and South
America.
West Nile Virus
Similar to Chagas and Babesiosis, West Nile Virus (WNV) is also an infection carried by
insect vectors, in this case, female mosquitos, who typically bite between August and
September and are endemic to the US. Historically, WNV primarily infected birds, but it has
since transferred to infecting humans and other mammals, like horses, cats, and other domestic
animals, further increasing the risk that local mosquitos will transmit the infection. The first
human WNV case in the US was reported in 1999, when individuals in New York City developed
meningitis and encephalitis. WNV spread to 10 states by 2001 with 66 cases, and by 2002, over
4,000 people were infected leading to nearly 300 deaths.100 WNV continued to spread through
the continental US, with nearly 10,000 reported cases in 2003, and over 250 deaths.100 By 2004,
WNV was reported in 47 states.100
WNV typically becomes symptomatic between 2 and 14 days following infection via
mosquito bite.100 Despite infection, nearly 80% of individuals will remain asymptomatic.100 The
majority of symptomatic individuals experience very mild symptoms, including fever, eye pain,
and body aches. 1 in 150 infected individuals develop the more severe form of the illness, and
75 between 4% and 14% of this population will die from the illness, with a higher mortality rate
seen in the elderly.100 There is currently no treatment for WNV, however, medications can be
given to reduce the effects of the symptoms.
The first case of ABT-related WNV transmission was reported in 2002.100 Between 2002
and 2003, over 50 cases of confirmed or suspected transfusion transmitted WNV were reported
to the CDC.100 In 2003, the FDA approved the first blood screen for WNV which could be used
in a blood collection setting.100 Blood banks joined the trial period on a voluntary basis. Since
then, WNV screening has become widely implemented, greatly increasing the safety of the
blood supply, and aiding in the reduction of infections nationally. While a huge step forward in
patient protection, it is suspected that 6 WNV infection blood components were released in 2003
despite testing negative for the infection.101 In retrospective analysis, these blood components
carried very low viral loads but were still infectious, as indicated by subsequent patient infection.
In 2009, the FDA published another guidance concerning WNV safety, encouraging the use of a
new NAT which used individual donor screening, ID-NAT, rather than mini-pool screening, MPNAT.101 This switch would increase sensitivity, but also increase costs and reduce resources. To
combat this conflict, the FDA encourages the use of MP-NAT followed by ID-NAT only if the
pool is reactive to the first screen.101 If the pool is not reactive to the MP-NAT, the FDA suggests
the entire group should be labeled negative and continue through the screening process. This is
a great example of utilizing technology to create the most efficient and cost-effective process
while still maintaining safety.
Unfortunately, this system failed in 2012 when a man receiving treatment for cancer
received WNV infected blood.102 The man subsequently died from encephalitis caused by the
WNV infection. When the situation was investigated, it was discovered that during the MP-NAT
the pool tested positive for WNV, but during the ID-NAT, none of the samples reacted. The IDNAT is considered the gold standard, so the results of that screen were used. Since this
incident, the blood bank and organizations involved in this situation have implemented a new
76 policy where an entire pool of blood is discarded if no positive samples can be identified after a
pool tests positive for WNV.102 This policy may lead to large amounts of waste depending on
their mini-pool size. This policy has not been nationally implemented, and WNV infections do
not ban an individual from donating for life, possibly mitigating the loss from this new policy.
If a donor tests positive during the screening process, they are not permanently removed
from the donor population. WNV can be successfully cleared from a donor’s system by their
own immune system, allowing them to continue donating after their complete recovery. The
FDA suggests donors should be deferred for 120 days (4 months) from the onset of symptoms
or the day of diagnosis, whichever was at a later date.100 After this deferral period, individuals
may reenter the donor population and the organization’s discretion. The current policies properly
reflect both the testing capabilities and the risks of the illness, making the WNV regulation
appropriate.
International regulations addressing WNV are reflected in deferral periods following an
individual’s return from the US. In all cases with data for regulations addressing travel to a WNV
endemic area, those that have a deferral period have one that lasts 4 CSF weeks. Some
countries also provided data about an individual’s reentry into the donor population after
successfully completing treatment for a WNV infection. These deferral periods vary, ranging
from 4 to 6 months. In the large majority of symptomatic cases, symptoms appear within 14
days of infection, making the 4 week deferral a proper reflection of this latency period while
accounting for a buffer period of human recall error. Not all countries have implemented the
WNV screen, because it is not cost-efficient in non endemic areas. Instead they depend on the
deferral after return from an endemic area or identification of the illness during the health
histories section of the blood collection process.
77 Increased Risk of Classic Creutzfeldt-Jakob disease or Variant Creutzfeldt-Jakob disease
from Travel, Clinical Exposures or Family History
• From 1980 through 1996, did you spend time that adds up to three (3) months or more in
the United Kingdom?
• From 1980 through 1996, were you a member of the U.S. military, a civilian military
employee, or a dependent of a member of the U.S. military?
• From 1980 to the present did you spend time that adds up to 5 years or more in Europe?
• From 1980 to the present did you receive a blood transfusion in the United Kingdom or
France?
• Have you ever received a dura mater (or brain covering) graft?
• Have any of your relatives had Creutzfeldt-Jakob disease?
Classic Creutzfeldt-Jakob disease (CJD), a fatal neurodegenerative disease, is most
commonly caused by a spontaneous mutation of normal prion proteins into abnormal prions.103
This incredibly rare disease affects one in a million people but is more likely to affect individuals
60 and over, where the incidence is 4.6 per million.103 While development of CJD is primarily
random, an estimated 5-15% of cases are caused by inherited mutations in the prion protein
gene.103 CJD is always fatal and progresses quickly causing early dementia and usually killing
an individual within 6 months of the first symptoms.103 Transmission of CJD has been recorded
in brain product transplants like a dura mater (brain covering) grafts and human pituitary-derived
growth hormone injections.53
Variant Creutzfeldt-Jakob disease (vCJD) is diagnostically unrelated, but physiologically
similar to CJD. Unlike CJD, which is endemic worldwide, vCJD has been associated with the
bovine spongiform encephalopathy (BSE) outbreak, also known as “mad cow” disease, in
Europe, specifically in the UK, where vCJD was first described in 1996.104 vCJD affects a
younger population than CJD, primarily being observed in individuals under 30. It also
progresses slower that CJD, usually killing the individual within 14 months.104 vCJD causes
“prominent” psychiatric and behavioral symptoms and “painful dysesthesias.”104 Consumption of
BSE infected beef puts individuals at a significantly higher risk for contracting vCJD, the human
form of mad cow disease. Since the end of 2010, 184,500 BSE positive cattle were identified,
effecting 35,000 different herds.105 Only a small portion of the infections were reported,
78 researchers estimate that, in total, approximately 4 million cattle were infected with BSE, and
3.3 million infected cattle entered Britain’s food supply.106 What concerns researchers the most
is the estimated 1 in every 2,000 Britons who now carry the human form of mad cow disease,
twice as many as previously thought in the late 1990’s.107 Little is known about disease
progression and latent period, which adds to the difficulty in creating policies which
appropriately protect the blood supply.107
Luckily, scientists have found that the prions, which cause the disease, were not as
dominate as previously thought, causing a much lower mortality rate than expected. This
suggests that many Britons are “subclinical carriers” of the abnormal prion, but will not develop
the symptoms associated with the fatal disease.107 Since 1995, 117 Britons have died from
vCJD.108 The majority of deaths took place between 1996 and 2004.108 The incidence of vCJD
has dramatically decreased, since 2012, only one death in the UK has been attributed to
vCJD.108 Additionally, there is not a single suspected or diagnosed case of vCJD currently alive
in the UK.108 Despite the lack of active cases, research conducted on a similar prion disease,
endemic to Papua New Guinea, found that prion diseases can remain latent for 50 years before
the individual develops symptoms.109 There is a very limited understanding of this disease, which has lead to an extra
precautionary response to other possible modes of transmission. The current understanding is
that the disease has never been transmitted through standard person-to-person contact (i.e.
cohabitation, shared cutlery, sexual intercourse, etc.). However, there have been at least 3
cases of transmission through a blood product donation from an asymptomatic donor.110 The
donors subsequently developed vCJD and died, but at the time of the donation, the individuals
had no clinical signs of vCJD.104,111 Researchers are unsure if subclinical carriers are able to
transmit vCJD through blood transfusions.107 In all of the cases of transfusion-transmitted vCJD
thus far, all of the donors were asymptomatic at the time of the donation, but did develop the
fatal disease soon after the donation. In 2013, experts in the UK estimated that up to 1,000
79 people will die due to tainted blood in their national blood supply.112 The limited knowledge
about the disease and the potential for an epidemic has encouraged the FDA to defer any
donors who are at an increased risk for vCJD. The absence of a blood test to screen for CJD
and vCJD means policy makers must depend on donor screening to protect the blood supply.
To avoid transmission of vCJD and CJD through blood transfusions, the FDA suggests a
permanent deferral of anyone who has been diagnosed with CJD, vCJD or BSE, and anyone at
an increased risk for exposure to the fatal illness. Factors that increase risk of exposure are:
•
•
•
•
•
Dura Mater transplants, Human Cadaveric Pituitary-Derived Growth Hormone, Cornea
transplants, and any other transplants where material could easily cross the blood-brain
barrier,
Xenotransplantation, or the transplantation, infusion, or implantation of animal organs,
tissues, or cells, for example bovine insulin,
blood products produced in the UK or France,
travel or residence to Europe, especially the UK,
and having blood relative who has been diagnosed with CJD, due to the genetic
inheritance risk.27
The travel policies factor in the different locations an exposure could take place, the range of
time an individual might be at highest risk, and the amount of time an individual had to spend in
that area to be considered high risk. They suggest that potential donors should be indefinitely
deferred if they have:
•
•
•
•
cumulatively spent three or more months in the UK between 1980 and 1996,
cumulatively spent five years in France between 1980 to the present,
have been former or current military personnel or civilian family members who resided at
a US military base in either Northern Europe (Germany, UK, Belgium, Netherlands) for
six months or more between 1980 and 1990, or elsewhere in Europe (Greece, Turkey,
Spain, Portugal, Italy) for six months or more between 1980 and 1996,
or if the have cumulatively spent five or more years in Europe since 1980.27
vCJD can remain undetected but still infectious within a carrier, so all individuals at an increased
risk of exposure should not donate. Additionally, anyone who received any type of blood product
transfusion while in the UK or France since 1980 is also indefinitely deferred, regardless of the
amount of time they spent in the countries.27
80 In terms of the US, BSE, vCJD, and CJD have had little effect on the population. In total,
there have been 4 cases of BSE in cattle, none of which entered the food supply due to the
“targeted surveillance” created to monitor BSE. Due to the lack of knowledge concerning
transmission, latent periods, and disease progression, the current CJD and vCJD regulations
will be considered appropriate, pending developments in blood testing and screening
technologies.
Table 22:
International
CJD and
vCJD
Regulations
Australia
Countries, Year
Range, and
Time Spent in
vCJD Endemic
Areas to Cause
Lifetime
Deferral
6 months in the
UK between
1980-1996
Austria
6 months in the
UK between
1980-1996
Belgium
6 months in the
UK between
1980-1996
Canada
3 months in the
UK or France
between 19801996, 5 years in
Western Europe
since 1980, 6
months in Saudi
Arabia between
1980-1996
Clinical Exposure
that Result in
Lifetime Deferral
Cases of
Iatrogenic
CJD
Family
History of
CJD
Blood transfusion in
the UK since 1980,
Bovine Insulin,
Human Growth
Hormone/ Human
Pituitary Hormone
before 1986
Blood transfusion or
other blood product
since 1980, Human
Growth Hormones/
Human Pituitary
Hormone
Human Growth
Hormone since
1986, Blood
Transfusion since
1980
Diabetics who have
used insulin before
2006, Dura Matter
9 cases (5
from Dura
Mater, 4 from
Gonadotropin)
Lifetime
deferral
4 cases (3
from Dura
Mater, 1 from
Growth
Hormone)
Lifetime
deferral
Lifetime
deferral
4 cases (all
Dura Mater)
Lifetime
deferral
81 England and
North Wales
No deferrals
Blood transfusion
since 1980, Human
Growth Hormone
before 1985
79 cases (65
from Growth
Hormone, 3
from Red
Packed Cells,
3 from
contaminated
surgical
instruments, 8
from Dura
Mater)
Lifetime
deferral
France
12 months in the
UK between
1980-1996
Blood transfusion,
Growth Hormone
before 1989,
Cornea transplant
before 2001
Lifetime
deferral
Germany
6 months in the
UK or Northern
Ireland between
1980-1996
Dura Matter,
Surgery or Blood
Transfusion in the
UK after 1980
133 cases
(119 from
Growth
Hormone, 1
from
contaminated
surgical
instruments,
13 from Dura
Mater)
11 cases (10
from Dura
Mater, 1 from
Cornea
Transplant)
Israel
6 months in the
UK between
1980-1996, 10
years in Portugal
or Ireland since
1980
Dura Matter, Human
Growth Hormone,
Blood Transfusion in
the UK since 1980
Italy
Japan
Spain
1 months in
England
between 19801996, 6 months
in Europe or
Saudi Arabia
since 1980
12 months in the
UK between
1980-1996
Lifetime
deferral
Lifetime
deferral
Human Growth
Hormone, Dura
Matter, Cornea
Transplant
Human Growth
Hormone, Dura
Matter, Blood
Transfusions
9 cases (all
from Dura
Mater)
Lifetime
deferral
142 cases (all
from Dura
Mater)
Lifetime
deferral
Human Growth
Hormones before
1987, Dura Matter,
Blood Transfusion in
UK, Bovine Insulin
14 cases (all
from Dura
Mater)
Lifetime
deferral
82 Sweden
Dura Matter
Switzerland
6 months in the
UK between
1980-1996
Blood Transfusion
after 1980, Human
Growth Hormone
before 1986
The
Netherlands
6 months in the
UK between
1980-1996
Blood Transfusion
after 1980, Human
Growth Hormone
United States
3 months in the
UK between
1980-1996, US
military and
civilian family
members who
spent 6 months
based in
Germany,
Belgium,
Netherlands
between 19801990 or Greece,
Turkey, Spain,
Portugal, Italy
between 19801996, 5 years in
Europe since
1980
Dura Matter, Bovine
Insulin produced in
the UK, Human
Growth Hormone,
Blood Transfusion in
the UK or France
since 1980
5 cases (3
from Dura
Mater, 2 from
contaminated
EEG Needles)
7 cases (5
from Dura
Mater, 2 from
Growth
Hormone)
34 cases (29
from Growth
Hormone, 1
from Cornea
Transplant, 4
from Dura
Mater)
Lifetime
deferral
Lifetime
deferral
Lifetime
deferral
Lifetime
deferral
Sources: Australian Blood Services, Osterreichisches Rotes Kreuz, Rode Kruis, Canadian Blood Services, Etablissement
Francais du Sang, DRK Blutspendedienst Niedersachsen, Sachsen-Anhalt, Thuringen, Oldenburg und Bremen,
Associazione Volontari Italiani Sangue (AVIS), Magen David Ado, 日本赤十字社 / Nihonsekijūjisha, Banc de Dang I
Texitits, GeBlod, Blutspende Srk Schweiz, Sanquimn Bloedvoorziening, National Health Services Blood and Transplants,
American Red Cross, United States Food and Drug Administration, AABB, Brown P, Brandel JP, Sato T, et al. Iatrogenic
creutzfeldt-Jakob disease, final assessment. Emerg Infect Dis. 2012;18:901-907.
There has never been a single case of vCJD that was not related to exposures in
Western Europe. For that reason, many countries have instated lifetime travel bans to reduce
the amount of potential vCJD carriers donating blood. The majority of countries reflect similar
policies regarding bans for vCJD and CJD. All countries with data, excluding the UK, have
lifetime bans for individuals who lived in the UK between 1980 and 1996, during the height of
the outbreak. However, the length of time residing in the high risk area varies from 1 month to
83 12 months. Many countries also include bans for living in countries who were in close proximity
to the UK, and suffered some of the same consequences of the mad cow outbreak in the 80’s,
including France, where 25 individuals have died from vCJD since the outbreak began, and
Ireland, who has experienced 4 vCJD related fatalities.
There is very little variation for regulations surrounding other risk factors for vCJD and
CJD. Between 5% and 10% of CJD are hereditary, leading regulators to instate a lifetime ban
on individuals with a familial history of CJD in every country. The other well known risk factors
also have little variation between countries, including lifetime deferrals for dura matter and
cornea transplants, and human pituitary growth hormone treatments. Those three procedures
account for over 450 CJD infections internationally. Any treatment which leads to transplant
material coming into contact with the brain or cerebral spinal fluid, a specific type of iatrogenic
infection, can put the recipient at risk. All other transplant materials would not allow the
abnormal prions to pass through the blood brain barrier, keeping the patient safe from infection.
Evidence suggests bans should be in place as a precaution for the transmission of vCJD and
CJD. Current international regulations properly reflect the potential danger of a contaminated
blood supply.
84 7. Exposure to Infectious Diseases: Sexually Transmitted Diseases (HIV/AIDS and Viral
Hepatitis Infections), and Other Infections (Bacteria, Virus, and Fungi)
The current policies surrounding exposure to HIV/AIDS and Hepatitis Viruses in the US
range from 12 months for tattoos and piercings, to a lifetime ban for IV drug users (IDU) and
men who have sex with other men (MSM). The main infections of concern are HIV, HCV, and
HBV. With any of these diseases, if an individual becomes infected, the specific mode of
transmission (i.e. via anal or vaginal sex, accidental prick with contaminated needle, or
cohabitation) has no effect on the length of time it would take for an individual to test positive
with the current screening. The difference between the exposures is the likelihood that an
individual would be exposed to the infections. The likelihood that an individual becomes infected
with HIV after getting an ear piercing is substantially different than the likelihood of an individual
becoming infected after having sexual intercourse with a prostitute. The concern arises with
newly infected individuals who might falsely test negative due to the window period, or the time
directly after infection, where an individual has not developed enough viral markers to test
positive, despite being infectious. The FDA has two groups of risk factors, those which allow for
reentry after a specific amount of time, and those that are too high of a risk for new infections so
the populations are banned from donating blood. The FDA has already detailed “high risk”
exposures that will cause a deferral but not a lifetime ban. For exposures that allow individuals
to reenter the donor pool, there is no scientific evidence that supports the need for deferral
periods that last any longer then the window period on the tests. Different deferral times for
different exposures remove potentially eligible donors from the population instead of allowing
them to attempt reentry as soon as the blood tests will read accurately.
FDA US Guidelines for HIV and Hepatitis Virus Exposures, Table 23
High Risk Activity
Contact with Blood- splash in eyes or mouth,
needle stick
New sexual partner
Multiple partners
Deferral Period After Last Exposure
12 month deferral
None
None
85 Prostitution- receiving compensation for sex
Engaging in sex with a prostitute
IV illicit drug user (IDU)
Sex with IDU
Non-injection illicit drug use
Piercing in a setting where sterility is
questionable
Tattoos in a setting where sterility is
questionable
Tattoo by licensed profession in sterile setting
Piercing by licensed profession in sterile setting
Incarceration
Sex with HIV positive individual
MSM
Females who have had sex with MSM
HIV-O exposure from habitation
HIV-O exposure from sex with individual who
was born or lived in HIV-O endemic area
HIV-O exposure from travel
HIV-O exposure from medical care in Western
Africa
HIV Infection
Hepatitis Infection- HAV
Hepatitis Infection- HBV
Hepatitis Infection- HCV
Hepatitis exposure from cohabitation
Hepatitis exposure from sex
Antibiotics
Lifetime
12 months
Lifetime
12 months
None
12 months
12 months
No wait if in a state that approves
tattoo parlors
No wait if in a state that approves
piercing parlors
12 months if stay was over 72 hours
12 months
Lifetime, probable switch to 12 months
after last exposure in near future
12 months
Lifetime if Cameroon, Central African
Republic, Chad, Congo, Equatorial
Guinea, Gabon, Niger or Nigeria after
1977, unless using specific FDA
approved test, ARC does not defer
Lifetime if Cameroon, Central African
Republic, Chad, Congo, Equatorial
Guinea, Gabon, Niger or Nigeria after
1977, unless using specific FDA
approved test, ARC does not defer
Lifetime if Cameroon, Central African
Republic, Chad, Congo, Equatorial
Guinea, Gabon, Niger or Nigeria after
1977, unless using specific FDA
approved test, ARC does not defer
Lifetime if Cameroon, Central African
Republic, Chad, Congo, Equatorial
Guinea, Gabon, Niger or Nigeria after
1977, unless using specific FDA
approved test, ARC does not defer
Lifetime deferral
Lifetime deferral if diagnosed with viral
hepatitis after their 11th birthday
Lifetime deferral if diagnosed with viral
hepatitis after their 11th birthday
Lifetime deferral if diagnosed with viral
hepatitis after their 11th birthday
12 months (HAV, HBV, or symptomatic
HCV, or unknown viral hepatitis)
12 months (HAV, HBV, or symptomatic
HCV, or unknown viral hepatitis)
No deferral after last dose of antibiotic
86 Other type of infection
Used clotting factor concentrates
Sex with someone who has used clotting factor
concentrates more than once
After complete recovery, varies by
collection site
12 months for one time medical use, 5
years if used multiple times
12 months
Source: U.S. Food and Drug Administration, American Red Cross, AABB
Direct HIV Exposure
•
•
In the past 12 months have you had sexual contact with anyone who has HIV/AIDS or
has had a positive test for the HIV/AIDS virus?
Have you ever had a positive test for the HIV/ AIDS virus?
The last confirmed case of HIV transmission via a blood transfusion was in 2008.114 The
case was investigated to find the source of error. The donor was contacted and researchers
discovered he had answered falsely to some of the questions during health histories. He
admitted that he often had anonymous sexual contact with both men and women while
intoxicated, and had done so prior to his donation.114 Due to the lack of time between his
infection and his donation, the donation occurred during the window period causing him to test
negative. Prior to this case, there have been three other cases of HIV infections caused by
blood transfusions since the addition of NAT.114 All cases have been linked to the window
period. The number of reported cases is significantly lower than the estimated risk of HIV
contraction via blood transfusion, which is approximately 1 in 2 million.114 The CDC suggests
this discrepancy is due to multiple factors, including under reporting, and the inability to rule out
other sources of infection. Additionally, a selection bias might be present due to the population
of people needing blood transfusions. Individuals who would require blood transfusions have a
significantly higher mortality rate than the general public, this suggests that many patients might
have died before any symptoms of HIV arose to suggest infection. While HIV positive individuals
only make up 0.16% of the US adult population, the effect on the blood collection market has
been remarkable.
87 Currently, 1.2 million Americans are infected with HIV, of those individuals, 1 in 7 are
unaware of their infection.115 The CDC estimates that approximately 50,000 Americans become
infected with HIV every year.115 HIV disproportionately effects minority races, males, MSM, IDU,
those who received blood products in the early 80s, and individuals in their 20s.115
African American and Black Americans experience the highest prevalence and incidence
of HIV infections compared to any other race. Despite accounting for 12% of the US population,
African American and Black individuals represent 44% of all new HIV infections and 41% of the
total HIV infected population.115 This is approximately 3.5 times more than their expected
representation within the infected population if the disease burden was uniform across races,
and 8 times more likely than white American males. The CDC states, 1 in 16 African American
male adults are infected with HIV.115 Latin Americans are also unequally represented in the
infected population. Males are 2.9 times more likely to become infected with HIV, and females
are 4.2 times more likely, than their white American counterparts.115
Women are significantly less likely to become infected with HIV. Female Americans
represent 23% of all living HIV positive individuals and 20% of new infections.115 The majority of
female infections are attributed to heterosexual sex and IV drug use, 84% and 16%
respectively.115 Females are twice as likely to become infected with HIV through heterosexual
sex than males after sex with an HIV positive partner. This is thought to be due to the increased
surface area of the vagina, and the fact that semen can remain within the vagina for days,
exposing the women for a longer period of time. There have been two well studied and reported
cases of transmission between women who have sex with other women (WSW) in the US.116
Both cases were closely observed to see if any other risk factors were present which might have
caused the infection and none could be identified in either case. Currently all scientific data
concludes WSW transmission of HIV is extremely unlikely.116 All large scale epidemiological
studies have never identified any infections within their study population that could be solely due
to WSW; often other risk factors, like injected drug use and heterosexual sex, were present.116
88 MSM Exposure
• (Female donors) In the past 12 months have you had sexual contact with a male who
has ever had sexual contact with another male?
• (Male Donors) From 1977 to the present, have you had sexual contact with another
male, even once?
In 2012, MSM accounted for 4% of the male population, however they represent 80% of
new HIV infections among males ages 13 and older.117 The MSM community has been hit the
hardest by the HIV/AIDS epidemic, accounting for 57% of the individuals living with HIV/AIDS in
2011.117 To make matters worse for this population, the number of infections in young MSM
increased by 20% between 2008 and 2010, and only 66% of the MSM HIV/AIDS population
were aware of their infection status.117 These statistics have been disproportionately high since
the outbreak of the epidemic, which led to a lifetime ban on all MSM if the activity happened
after 1977. The lifetime ban on MSM is estimated to eliminate 2,600,000 otherwise eligible
donors from the population.118 If the ban were to be lifted, an additional 3.5 million blood
products are predicted to be added to the national blood supply annually.f
The MSM lifetime ban has been a controversial topic, especially since 2013, when
Senator Warren and 86 other congress and senate members sent a letter to the Department of
Health and Human Services calling for an end to the MSM ban. The letter makes use of
evidence-based studies from the American Medical Association (AMA) and the Advisory
Committee on Blood Safety and Availability, and concludes that the MSM ban is “medically and
scientifically unwarranted.”119 Senator Elizabeth Warren has publically stated, "For me, this has
been a basic issue of fairness and of science - blood donation policies should be grounded in
science, not ugly and inaccurate stereotypes.”120 The FDA has finally responded to the
Congressional pressure, and in 2015 announced plans to repeal the lifetime ban in favor of a 12
month deferral since a male individuals last male sexual encounter.
f
10% [percent of population who donate blood]/ 38% [current percentage of population that is eligible to
donate] = 0.26 X 2,600,000 [number of individuals who would be eligible to donate if the MSM ban is
lifted] = 684,210 X 1.7 [average number of donations an individual makes per year]= 1,163,157 X 3
[maximum number of blood products that can be made from a single donation] = 3.5 million additional
blood products in the national supply
89 Replacing the lifetime ban with a 12-month deferral rate sets a new acceptable risk rate
for active donors. Once again, the mode of transmission has no effect on the ability for the blood
screens to test for the infection or the possibility of spreading the infection to other individuals.
Once MSM activity has been moved into the “high risk” but not banned group, the level of
acceptable risk will change drastically. The MSM community makes up 2% of the US population
but 57% of the existing HIV infected population, 28.5 times their expected proportion if sexual
preference had no effect on the likelihood of infection. The proposed switch from a lifetime ban
to a 12 month deferral has raised the allowed risk rate to nearly 30.
Sub-Saharan Africa Exposure
• Have you ever been in Africa?
Sub-Saharan Africa has been the hardest hit area in the world, accounting for 70% of all
HIV infections internationally.121 In 2012, 25 million individuals living in Sub-Saharan Africa were
living with HIV.121 Additionally, 1.2 million Africans died of AIDS-related complications, and 1.6
million Africans became infected.121 Unlike the US, the majority of infected individuals in this
region are women. Adding to the burden, less than 40% of HIV positive individuals are receiving
treatment.121 Due to this high prevalence of HIV, individuals who were born, or lived in SubSaharan Africa are subject to a lifetime deferral with some organizations. This concern is due to
a rare strain of HIV, HIV-O, which is endemic to Western Africa. While the most current tests
have been able to detect HIV-O, some countries are still skeptical and have deferral periods for
individuals who have traveled and immigrated from Sub-Saharan African, as well as their sexual
partners. ARC has no deferrals related to travel to HIV endemic areas, however, many of the
same areas are also ME areas and consequently cause a deferral for that exposure.
Not only do the deferral periods differ, but the way countries distinguish between
exposed and unexposed varies greatly as well. Austria has implemented a lifetime ban on
individuals who spent at least 6 months in an area where HIV positive individuals make up more
than 1% of the population. Canada specifies a lifetime deferral based on the individual’s place of
90 birth. They deferral individuals who were born in Cameroon, Central African Republic, Chad,
Congo, Equatorial Guinea, Gabon, Niger, and Nigeria since 1977, in addition to their sexual
partners. Other variations are seen in Belgium and Germany, who defer individuals who have
spent 6 months or more in a HIV-O endemic area. However, the deferral periods between these
two countries differs greatly; Germany’s policy is a 4 month deferral, while Belgium’s policy is a
5 year deferral.
The data available for this topic are limited, and the reasoning for this is unclear. Many
countries do not have any policies regarding travel or immigration to Africa, while others do but
this only becomes evident after an extensive questioning about travel during the health histories
process. The lack of consensus for this policy suggests a lack of understanding about the true
risks of HIV-O. Many policymakers see Africa as the source of new strains, and worry that
current tests will not be able to pick up strains which have never been seen in America before.
However, scientists ensure the tests are generalized to test for HIV, not each specific strain,
maintaining their safety. Due to the fact that this policy is based in prediction as much as it is
based on past experience, this amount of variation is not surprising. In this situation, the US
policy is one that appropriately represents the available data, allowing individuals from Africa to
donate if the tests are approved by the FDA for this purpose.
Direct Hepatitis Exposure
• In the past 12 months have you had sexual contact with a person who has hepatitis?
• In the past 12 months have you lived with a person who has hepatitis?
• Have you ever had hepatitis?
Hepatitis infections are characterized by inflammation of the liver, often caused by a
virus, and is the leading cause for liver cancer and liver transplantation. An estimated 4.4 million
Americans are currently living with chronic Hepatitis, the majority of these individuals are
unaware of their infection status.122 There are five main types of Hepatitis viruses: Hepatitis A
Virus (HAV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Hepatitis D Virus (HDV), and
Hepatitis E Virus (HEV).122 Hepatitis A and E are most commonly caused by ingestion of
91 contaminated food or water, while the other three types are associated with exposure to bodily
fluids.122 HBV and HCV are the most concerning for blood safety because they lead to a chronic
form of Hepatitis which can be easily passes through blood to blood contact decades after the
primary infection.122 HDV is uncommon in the US, and is caused by an RNA-structured virus
which can only infect individuals who are already infected with HBV, which aids the HDV in
replication.122 HEV is also very uncommon in the US but is common in many other parts of the
world.122 Both HDV and HEV are serious liver infections with long term health effects.122
Viral Hepatitis A, B, and C Risk Factors, Prevalence, Incidence, and Fatalities, Table 24
HAV
HBV
HCV
Risk Factors
MSM, IDU,
International
Travelers,
however nearly
50% of individuals
infected in the US
have no risk
factors
MSM, unprotected
sex with multiple
partners, IDU,
history of other
STI’s
Blood
transfusions, IDU
Prevalence
HAV is not a chronic form
of Hepatitis, 10%-15% of
HAV infected individuals
will experience a relapse
of symptoms within the 6
months after infection
Incidence
3,000
estimated acute
(new) infections
in 2012
Fatalities
80 individuals in the
US with HAV listed
as COD in 2013
0.7- 1.4 million chronic
cases in the US in 2012
18,800
estimated acute
(new) infections
in 2012
1,873 individuals in
the US with HBV
listed as COD in
2013
2.7- 3.9 million chronic
cases in the US in 2012
24,700
estimated acute
(new) infections
in 2012
19,368 individuals
in the US with HCV
listed as COD in
2013
Source: Centers for Disease Control and Prevention, Division of Viral Hepatitis
The US federal law allows individuals who have been infected with HBV before their 11th
Birthday to donate if fully recovered. However, this does not reflect the current knowledge about
HBV. Only a portion of HBV infections become chronic, and the likelihood of this happening is
inversely related to the individual’s age. Studies have found 90% of infected infants and 30% of
infected children under 5 year old develop chronic HBV.122 This is compared to between 2% and
6% of adults whose acute HBV infections become chronic.122 HBV can be transmitted through
blood transfusions even if the donor is asymptomatic.
92 HCV often goes undiagnosed because 60% to 70% of newly infected individuals
experience mild symptoms, if any.122 15% to 25% of HCV infected individuals will spontaneously
clear the infection from their body without treatment, but the cause of this immune response is
relatively unknown. Chronic HCV infections develop in 70% to 85% of cases, however only 60%
to 70% of chronically infected individuals have diagnostically relevant liver disease.122 The
majority of HCV transmissions occur through blood to blood contact, like blood transfusions or
IV drug use. The association between infection and sexual activity has been less clear. Some
studies have estimated that 15% to 20% of HCV infections occurred in individuals with multiple
sexual partners with no history of IV drug use or blood transfusions.122 These findings suggest
HCV infections are possible through sexual contact, but are less efficient at transmitting the
disease, compared to other sources of infection. Additionally, HCV is not more prevalent in
MSM than heterosexual males.122 However, co-infections of HCV and HIV are relatively
common, especially for IDU, HCV infections are reported in 50% to 90% of HIV positive IDU.123
HCV effects HIV positive individuals in a much more aggressive way and causes liver damage
and disease quickly, often resulting in death.
International comparison exposed uneven degrees of variation between responses to
HAV, HBV, and HCV infections. All countries that specified by type, which was all but Israel,
which stated they had a 5 year deferral for Hepatitis infections, had a lifetime ban on HCV. The
two exceptions for this finding was Spain and the US, which allowed individuals who contracted
HCV were last diagnosed their 12th and 11th birthday, respectively, to donate. This means
individuals who contacted HCV before a specific age, and have not shown any signs of chronic
infection since, can donate normally when they become of age. HAV and HBV had significantly
more variation. HAV deferrals ranged from 3 months after recovery, a policy found in the
Netherlands, to a lifetime deferral, as with the US’s policy banning all forms of viral hepatitis,
including Epstein Barr Virus. The slight majority of countries had a deferral of 6 months following
recovery from HAV. When looking at HBV, the large majority of countries, including the US if
93 14 12 Deferral After Sex with a Viral Hepatitis Carrier, Figure 25 12 Months 10 8 6 4 Strictest Average Most Lenient birthday, had lifetime ban. Sweden and
Belgium both allowed HBV individuals to
12 reenter the blood donor population once
8.3 blood tests showed no signs of infection.
4 4 2 0 US Regulation contracted after an individual’s 11th
International Regulations (n=12) *Does not include Italy, which has a lifetime ban ScientiSic Evidence Variation between lifetime bans and the
possibility of donor reentry greatly effects
the country’s overall donor population.
Deferrals based on exposure showed dramatic amounts of variation as well. Deferrals
after sexual activities with a Hepatitis carrier ranged from 4 months, in Austria, France,
Germany, and Spain, to a lifetime ban in Italy. When the lifetime ban is excluded from the data,
the average deferral for international collection organizations was 8.3 months, compared to
US’s much stricter policy of 12 months. Deferral after cohabitation closely paralleled the deferral
after sexual exposure and can be found in the Appendix.
Exposure through Broken Skin
• Have you ever used needles to take drugs, steroids or anything not prescribed by your
doctor?
• In the past 12 months have you come into contact with someone else’s blood?
• In the past 12 months have you had an accidental needle-stick?
• In the past 12 months have you had a tattoo?
• In the past 12 months have you had ear or body piercing?
Blood to blood exposure via contaminated needles during a piercing, while receiving a
tattoo, or while injecting drugs is a possible way to transmit HIV/AIDS and the Hepatitis Viruses.
STI’s are transferred through blood to blood contact and require only a small amount of virus to
become infected. IDU account for 8% of new HIV infections and 15% of all HIV positive
Americans. The best estimate for the number of IDU in the US is approximately 2 million, or
0.65% of the population.124 Therefore, the actual population of IDU who are HIV positive is 16
times the expected population if the activity was not a risk factor.
94 The risk of infection after exposure through a needle prick varies by infections. There is
no risk of HBV infection after a needle stick contaminated with HBV infected blood if the
individual who was exposure has received a Hepatitis B Vaccine or receives one directly after
expsoure.125 If they have not, such an exposure would cause 6% to 30% of the individuals to
become infected with HBV, depending
Deferral Period After Peircing in Possibly Unsterile Setting, Figure 26 12 on the antigen status of the HBV blood
source.125 HCV carries less risk for
12 Months 10 transmission. Studies have found only
8 4.4 4 2 1.8% of individuals who are stuck with
6 6 4 US Regulation Strictest Average Most Lenient International Regulations a needle contaminated with HCV
4 ScientiSic Evidence n=14 Deferral Period After Exposure to Another Person's Blood, Figure 27 12 12 10 Months However, IDU lifestyle of frequent
exposure over a long period of time
has made HCV very common within
14 12 infected blood will develop HCV.125
8 6 6 4 4 Strictest Average Most Lenient this population, effecting
approximately one third of IDU
between the ages of 18 and 30, and
4 2 0 US Regulation International Regulations n=14 ScientiSic Evidence 70% to 90% of older or former IDU.125
The spread of HCV via shared
needles peaked in the 70s and 80s
before individuals were educated about the risk of blood borne viruses.125
HIV has the lowest risk for infection after a needle stick contaminated with HIV/AIDS
positive blood. On average 0.3% of individuals who are stuck with a HIV contaminated needle
will develop HIV.125 It is important to note these are the risks if an individual is stuck with a
needle that positively contains infectious amounts of the viruses, not the risk that a needle
95 would be contaminated, which would vary based on location, type of needle exposure, and
14 hygiene routines.
Deferral Period After Tattoo in Possibly Unsterile Conditions, Figure 28 12 Exposure to contaminated blood
12 through a splash in the eyes or mouth,
Months 10 contact with skin, or drops close to a
8 6 4.7 4 6 4 2 0 US Regulation Strictest Average Most Lenient International Regulations open cut rarely leads to any type of
4 infection. Only a few cases of HCV and
HBV transmissions have been reported
ScientiSic Evidence n=13 from blood to eyes, mouth, or skin
contact, however, while very rare, it is possible.125 The risk of a HIV infection after HIV blood
comes into contact with an individual’s mouth or eyes is on average 0.1%.125 Exposure to HIV
infected blood coming into contact with intact skin is expected to pose a very small risk, less
than 0.1%.125
There is very little variations between countries’ policies regarding drug use. In 14 out of
the 15 countries included in the comparison, illegal IV drug use led to a lifetime deferral for the
presenting donor. Some countries also have deferrals for exposures due to non-IV illegal drug
use, like cocaine and marijuana. When discussing these specific regulations with a blood
collection organization representative from a country with deferrals for non-IV illegal drug use,
they explained that while the action itself was not a risk factor for TTI, the activity suggests the
individual is more likely to partake in other high risk activities that would increase the possibility
of acquiring a TTI.58 This would make the use of non-IV drugs an indicator for the existence of
other risk factors, rather than a risk factor itself.
96 Exposure through Sexual Activities with High Risk Individuals
• In the past 12 months have you had sexual contact with a prostitute or anyone else who
takes money or drugs or other payment for sex?
• From 1977 to the present have you received money, drugs, or other payment for sex?
• In the past 12 months have you had sexual contact with anyone who has ever used
needles to take drugs or steroids, or anything not prescribed by their doctor?
• Have you ever had sexual contact with anyone who was born in or lived in Africa?
• In the past 12 months have you had sexual contact with anyone who has hemophilia or
has used clotting factor concentrates?
Unprotected sex is the major source of HIV transmission. The likelihood of becoming
infected with HIV during anal intercourse depends on whether the HIV individual is receiving
anal intercourse from an HIV positive individual, in which case the risk is 1.4% (1 in 77
exposures), or the reverse, where the HIV positive individual is the inserting partner.126 The
likelihood for the insertive partner to receive HIV from an HIV positive recipient during anal sex
varies. For circumcised men, the risk is 0.11% (1 in 909 exposures), uncircumcised men have a
much higher risk of 0.62% (1 in 161 exposures).127 Women involved in insertive vaginal sex with
an HIV positive male is estimated to be 0.08% (1 in 1,250).128 Heterosexual sex for males is less
risky then homosexual insertive sex, with a risk of 0.04% (1 in 2,500).128 However, it is important
to note these are only averages and there are many different factors which can effect the
likelihood of transmission. It is known that during the acute HIV infection, in the weeks following
an individuals infection, they are far more likely to spread the infection. This is due to two
reasons. One, because the majority of individuals are unaware of their infection at this point and
may not be taking proper precautions, and secondly, an individual’s viral load is much higher
directly after infection. A 10-fold increase in viral load is associated with a 2 to 3 times increased
risk of transmitting the disease.129 The risk of a newly infected male transmitting HIV through
penetrative vaginal sex is up to 2% (1 in 50) and through penetrative anal sex, up to 20% (1 in
5).130 Other factors can also increase the likelihood of infection, including other current STI’s,
menstruation, and rougher sex, which might cause abrasions or tearing.130 It is unknown what
the true risk for transmission through performing oral sex is, however it is assumed to be
97 increased for individuals who have recently brushed their teeth, flossed, or any other activity
which might cause small cuts in the mouth.130
HBV is 50 to 100 times easier to transmit than HIV.131 However, HBV is the only STI that
has a vaccine to prevent infection.132 This vaccine can also be taken directly after exposure to
greatly reduce the likelihood of an infection.132 Unlike HBV, the risk of HCV has long been
disputed. Very few cases have ever been reported where the only risk factor has been
unprotected sex.130 Due to the very small prevalence, a true risk rating is unknown.130
Policies that address sex with any high-risk individual are largely focused on reducing
the possibility of an donor unknowingly transmitting the disease because they themselves do
not partake in the high risk activity. All countries have some policies that implement deferral
periods after sexual activity with a high risk individual. These deferral lengths are highly variable
and can be seen in Figure 29. If these policies properly reflected scientific data you would
expect all exposures to be no more than 4 months, which on the graph would show as only the
orange column. This is not what is seen through analysis, and instead huge amounts of
variation is observed. A red dot has been placed over the column in which the US regulation is
included. In the majority of the cases, the US is included within the majority however there are
also very few countries with stricter policies. This would then mean in the majority of the cases,
9 out of the 10, the US is above the international average. The outlier policy is based on sex
with a new partner that does not partake in any high risk activities. In this case the US is still
within the majority, however there are countries with a deferral policy, increasing the
international average, and making the US fall below the average, as more lenient.
The policies regarding exposure to TTI after sexual activities with a high risk individual
do not properly reflect the scientific data available. If policymakers decide to implement a
temporary deferral, instead of a lifetime deferral, it should reflect the maximum amount of time
necessary for the tests to read positive, especially for infections that commonly go undiagnosed
for long periods of time.
98 Deferral Period After Sex with a "High Risk" Individual by Deferral Length, Figure 29 Unknown Lifetime 5 years 12 months 6 months 4 months None Number of Countries with Regulation (n=15, including US) 9 8 7 6 5 4 3 2 1 0 HIV Positive Partner MSM Female MNM Hep Positive Partner Born in New Partner Partner is/was Partner is IV Partner Africa a Prostitute Drug User Type of Exposure Partner is Partner uses Hemophilic Clotting Factors US Policy Evidence-­‐Based Policy Incarceration Exposure
• In the past 12 months have you been in juvenile detention, lockup, jail or prison for more
than 72 hours?
HCV is a huge problem within the incarcerated community. There are currently 2.2
million Americans in jails or prisons, and a third of them are infected with HCV.133 Incarcerated
individuals are also 2.4 times more likely to be HIV positive than the general public.134 In 2008,
1.4% of incarcerated individuals were living with HIV/AIDS, totally nearly 22 thousand in both
federal and state prisons.134 The majority of HIV positive individuals contracted HIV before they
were incarcerated, but many of them received their first diagnosis by the prison doctors.134 For
those that contract HCV and HIV while incarcerated, modes of transmission are through
consensual or forced sex, exposures through shared contraband and drug paraphernalia, and
contaminated needles for tattoos and piercings. Additionally, the infections cannot be killed
through boiling, heating or cleaning with common cleaners like peroxide or alcohol, making the
disease even easier to spread in situations with limited resources.133 This tells policy makers
that incarceration is not specifically a risk factor, but it is an indicator for other high risk activities
which are more prevalent in that population.
Similar to the way some countries use illegal non-IV drug use as an indicator for high
risk activities, incarceration time is also an used as a possible characteristic of individuals at an
elevated risk for TTI. Less than half of the countries included in the study have deferral policies
based on incarceration, they are Australia, Canada, Germany, and the US. The US is one of the
strictest countries in comparison to the other countries involved in the study simply by the fact
that the regulation exists. Using the notion that acceptable risk is the highest risk associated
with a non-deferred donor population, African American and Black individuals are 8 times more
likely to contract HIV than white Americans. Race is a stronger risk factor for HIV than
incarceration, which is associated with an increased risk of 2.4. However, incarcerated
individuals are 30 times more likely to be infected with HCV than the general public, which is a
significant risk.
Clotting Factor Concentrate Exposure and Other Contaminated Blood Products
• Have you ever used clotting factor concentrates?
Contaminated blood products date back to the 60’s where individuals receiving a blood
transfusion had a 33% chance of contracting HCV.135 Tainted blood products were one of the
first identified sources of infectious disease transmissions associated with the AIDS epidemic.
Between the late 70’s and mid 80’s between 6,000 and 10,000 hemophiliacs became infected
with HIV, and 6,000 to 10,000 hemophiliacs became infected with HCV.135,136 Both infections
had contaminated the clotting factor concentrates hemophiliacs used for treatments. In 1985, a
technique to treat clotting factor concentrates for HCV and inactivate any potential virus became
available, and by 1987 it was widely used, nearly removing the HCV risk associated with the
treatment.135 In the late 90’s a tainted supply of clotting factor concentrates caused a small
outbreak of HAV, resulting in 4 cases and a major recall of affected products.137 This specific
outbreak was thought to be caused by an asymptomatic newly HAV infected blood donor.
The incredibly sophisticated screens and tests available have reduced the risk of HIV
and HCV infection from blood products to 0.72 and 0.5 per one million transfusions,
respectively.138 However, exposure to clotting factor concentrates can be a deferral period
between 12 months and a lifetime ban, depending on the collection site. This incredibly small
risk is well below some of the other non-deferred risk factors, like race, age, and new sexual
partners, making this policy not scientifically warranted if using previous policies as a gauge for
acceptable risk. Unexpectedly, all of countries with data available for clotting factor concentrate
use have a lifetime ban in place. However, these products are used to treat bleeding disorders,
like hemophilia, which would lead to a lifetime deferral regardless of whether or not the
individual used clotting factors. While these policies may not properly reflect the risk of TTI in
this population, the population should still be deferred for their own safety and because their
blood would not be useful for a transfusion.
101 All Exposures
Even though risk factors supported the exclusion of individuals involved in “high risk
behaviors” in the past, testing capabilities make it possible to reduce the deferral times greatly
to only account for the window period. Using the most sensitive tests available, the HIV and
HCV eclipse periods have been reduced to between one and two weeks. ARC states that due to
their testing methods and mini-pooling process, their testing window for HIV has been reduced
to 9 days. Typical blood screening for donated blood include multiple tests for HIV, which all
measure different indicators for the disease. This is done to account for anomalies some
individuals have, like the ability to control their viral load, or the lack of antibodies. Currently, the
longest window period for one of these tests is 6 weeks. HCV and HBV testing has experienced
the same technological advances as HIV testing. HBV testing has reduced the window period to
generally the same time span as HV testing, however, HCV still has a relatively lengthy window
period of 4 to 10 weeks. Because of this longer window period, deferrals for these infections
must reflect the HCV, rather than the HBV or HIV, window period.
The difference in deferral lengths due to type of exposure does not properly
reflect the screening capabilities or latency periods for diseases, making these exposure
deferrals too strict (see table 33 for a more specific breakdown of labels). An individual who
contracted HIV through MSM activities and an individual who contracted HIV through sex with a
hemophiliac will have the same risk of testing negative despite their infectious status 3 weeks
after infection. The specific mode of infection is irrelevant, therefore different deferral lengths for
different possible sources of infection do not reflect the capabilities of current screening
technologies and the advancing knowledge about window periods. If organizations are using
gold-standard screens and tests, the maximum deferral length should be no more than 4
months, allowing for a month of buffer time for HCV as a precaution.
High risk activities are separated into two groups, those that cause a temporary deferral
and those that cause a lifetime deferral. Lifetime deferrals should be done in cases where it is
102 thought to be inefficient due to the amount of wasted resources collecting contaminated blood
which must then be removed and destroyed. This is applicable in the case of IDU, where one
third of the population is infected with HCV. In this situation, a third of the resources being used
to collect blood from this population will have been wasted because the collected blood is not
usable. Once high risk categories are separated into these groups, the risk factors associated
with each activity must properly reflect the range of acceptable or unacceptable waste and risk.
The large majority of countries agree that individuals with HCV, HBV, or HIV, IDU, MSM,
and individuals who have been compensated for sex (engaged in prostitution) should all be
deferral for life. A smaller majority of the countries also have a lifetime ban for individuals who
have used clotting factor concentrates more than once. The rest of the risk factor deferral
periods vary greatly among the countries involved in this study, and range from one month to
five years or indefinitely. On average, the US was either equal to or higher than the strictest
international policy for the majority of the risk factors. Most of the European countries included
in the study, Austria, Belgium, the Netherlands, Italy, Spain, Germany, France, and Switzerland,
were closer to reflecting the testing capabilities and, therefore, had more appropriate
regulations. Overall, the US’s policies meant to protect the patient from HIV and the Hepatitis
Viruses are too strict, do not properly reflect the current scientific data, and are greatly reducing
the national blood supply.
103 Deferral Period After Cessation of "High Risk" Activities by Number of Countries with Regulation, Figure 30 Unknown Lifetime 5 years or After Complete Recovery 12 months 6 months 3-­‐4 months </= 1 month -­‐ None Number of Countries with Regulation (n=15, including US) 16 14 12 10 8 6 4 2 0 Type of Exposure US Policy Evidence-­‐Based Policy Other Infections
•
•
Are you currently taking an antibiotic?
Are you currently taking any other medications for an infection?
Antibiotic use by donors is not a concern to recipients of blood products. In fact, half of
the individuals in inpatient care are given antibiotics as treatment, a quarter of them are on two
or more different types of antibiotics.139 The concern surrounding antibiotic use is the
transmission of the infection the antibiotics are treating. Any type of infection can be lethal to
those with compromised immune systems.
The contagious period for viruses varies with different types of illnesses, symptoms, and
an individual’s immune system. The flu has been found to have a short contagious period of, on
average, one day, according to a study published in 2012.140 The study also found that less than
5% of individual’s were contagious for more than 2.9 days.140 Researchers concluded isolating
the ill individual for 16 hours after the symptoms arose would prevent 50% of the secondary
infections.140 Most medical professionals suggest a 24 hour isolation period following the onset
of symptoms to reduce the spread of the flu.141 Some more serious viruses, like mononucleosis,
tuberculosis, and meningitis, can be infectious for weeks following the first symptoms.141 The
general understanding with viruses, like the flu, the common cold, and coughs, is that once the
fever has subsided, the individual is no longer contagious.141 In most common viruses the
contagious period begins with the primary symptom of the illness.141 For example, the common
cold becomes contagious once mucus begins to accumulate in the nose, and ends when the
fever is resolved. It is the same principal for a virus that causes a cough, beginning with the
cough and ending with the resolution of the fever. Once the temperature has returned to normal,
after 24 hours, the majority of common viruses are no longer infectious, despite any residual
symptoms.141
For bacterial and fungi
Deferral Period After Completion of Antibiotic Use, Figure 31 infections being treated with
30 antibiotics, it only takes 24 hours
25 Days after the first dose for an individual to
Strictest Average 10.2 Most Lenient 0 0 International Scienti=ic Evidence Regulations (n=13) 28 20 stop being contagious.141 While the
15 majority of infections are neutralized
10 after 24 hours on antibiotics, ARC
5 requires individuals to finish their
0 0 US Regulation regimen of treatment before
donating blood.53 This is to make sure the donors have been completely cured of the infection,
and to make sure the donor is healthy enough to withstand the blood loss. This regulation
properly reflects the current understanding of infectious periods and antibiotic use,
making this policy an appropriate representation of evidence-based science.
Despite large amounts of data on latency periods and contagious periods, and well
understood physiological mechanisms, there was still a large amount of variation between the
countries included in the study. The deferral period for antibiotic use was one of the most
inconsistent policies observed. The average, deferral time was 10.2 days, however, the range
spanned from no deferral after the treatment was complete, in the case of Canada, the US, and
Spain, to 28 days for Germany and Austria. The most common deferral period was 14 days,
which was the case for France, Italy, Sweden, Switzerland, and the Netherlands. These specific
results were relatively surprising, and not consistent with the availability of data, nor reflective of
current knowledge.
106 Study-Wide Themes Between US Policies, Scientific Data, and International Policies
Of the 50 different policies observed during this study, 14 were policies meant to
increase the safety for the patient receiving the blood, and 36 were meant to protect the donor
from an ADR. The US treats the safety of the donors and the safety of the patients receiving the
transfusion very differently. When the two groups were compared to the average of the
international policies, two opposing themes became evident.
Policies to Protect the Donor
10 out of the 14 US policies (71%) meant to protect the donor, were more lenient in
comparison to the average international policy. Out of the remaining 4 policies, 2 were average
in comparison, and 2 were stricter in comparison. The US policies to protect the donor are
meant to reduce the amount of ADR, which can reduce the donor population, cause health risks
to the donors and those around them, and cause inefficiencies in the collection process when
nurses have their time consumed by tending to ADR, rather than continuing to collect blood.
In many cases, the US was the most lenient in the comparison, as seen in the lower limit
for systolic blood pressure, maximum age for RD and FTD, deferral after childbirth, heart and
lung issues, cancer, and diabetes. When the US was not below the most lenient international
country included in the study, it was either equal to the most lenient (as was the case for
diastolic blood pressure minimum, volume of blood collected, minimum amount of days between
donations for both men and women, and minimum age for FTD) or below the average of
international collection organizations (like in the case of the minimum hemoglobin level for men).
Only two US policies were equal to the strictest international policy, minimum hemoglobin level
for women, and blood pressure upper limit.
Policies to Protect the Patient
The US has extremely strict policies concerning patient safety, especially in comparison
to many of the European countries. These discrepancies seem to stem from an unnecessarily
long deferral period for exposures related to HIV and Hepatitis Viruses, which are most likely a
107 reflection of the eclipse period for outdated and replaced blood test. Additionally, the social
stigma behind TTI like HIV and the Hepatitis Viruses may also influence policymakers to
develop stricter regulations to put worried constituents at ease. Of the policies meant to protect
the patient, 17 were strict, 15 were appropriate, and 5 were lenient. This is a completely
different pattern then the relationship between level of leniency and protection of donors.
Deferring an individual for 4 months versus 12 months makes no difference in risk to the
patients receiving the blood, because both would have the same level of risks for false
negatives, or other systematic errors. Furthermore, with many of these illnesses, individuals
either become aware of their condition during the acute phase, often in the few weeks following
the infection, or they find out through an unrelated blood test, STI test, or, for some, when
donating blood. Many people with chronic diseases like HCV and HIV can go years without
being aware of their condition. Therefore, a longer deferral period will not increase the likelihood
that an individual will become aware of their infection before they are eligible again and refrain
from donating. With the implementation of NAT, the only outcome of longer deferral periods is
preventing individuals from entering the donor population for several additional months. Deferral
periods longer than the eclipse period, that are not lifetime bans, are scientifically unwarranted,
and increase the inefficiency of the system.
108 Diagram of Policies’ Relationships to Scientific Evidence and International Regulations, Figure 32 Stricter than scientific data suggests regulations should be
-Pulse
-IV Drug Use
-Lower Blood Pressure Limit
-Lower Age Limit
-Volume of Donation
-Frequency of Donation
-Male Hb Lower Limit
-Cancer
-Diabetes
-Malaria Exposure from Residence
-Hepatitis Exposure from
Cohabitation orSexual Partner
-vCJD and CJD Clinical Exposure - Upper Blood Pressure Limit
-vCJD Travel Exposure
-CJD Family History
-Chagas Disease
-West Nile Virus
-Babesosis
-Non IV- Drug Use
Stricter than international average regulation
-Upper Age Limit
-Heart and Lung Issues
-Malaria Infection
-Peircing or Tattoo in
Sterile Environment
-HIV-O Exposure from
Travel or Sexual Partner
-Antibiotic Use
-Recovery from infection
-Temperature Range
-Female Hb Lower Limit -Jail
-Engaging in Prostitution -MSM
-Female MSM
-Sex with a Prostitute
-Sex with an IV Drug User Exposure
-Malaria Exposure
-Peircing and Tattoo in
-Contact with Blood
Unsterile Enviroment
- Sex with HIV Positive Partner
-Use of Clotting Factors
-Sex with Hemophiliacs or
Individuals who Use Clotting
Factors
-Weight
-New Sexual Partner
-HCV Infection
-HBV Infection
Regulations to Protect the Donor
Regulations to Protect the Patient
109 Summary of Results, Table 33
Regulation
Topic
Classification
Categorization
Pulse
Strict
Blood PressureUpper Limit
Blood PressureLower Limit
Age- lower limit
Appropriate
Age- upper limit
Appropriate
Volume of
Donation
Frequency
Lenient
Weight
Lenient
HemoglobinFemale
HemoglobinMale
Heart and Lung
Problems
Pregnancy
Strict
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Donor
Protects the
Patient
Protects the
Patient
Protects the
Patient
Protects the
Patient
Protects the
Patient
Protects the
Patient
Protects the
Patient
Protects the
Patient
Cancer
Diabetes
Malaria- Travel
Lenient
Lenient
Lenient
Lenient
Unknown,
Appropriate
Unknown,
Lenient
Unknown,
Lenient
Unknown,
Lenient
Strict
MalariaResidence
Malaria- Infection
Lenient
vCJD- travel
Appropriate
CJD- family
history
vCJD and CJDclinical exposure
Chagas Disease
Appropriate
Babesiosis
Appropriate
Appropriate
Appropriate
Appropriate
Comparison to
International
Average
Average
Most Lenient
Country (with
data available)
UK
Stricter
UK
More Lenient
UK
More Lenient
Australia, US
More Lenient
US, Austria
More Lenient
US
More Lenient
US, Canada
Average
n/a
Stricter
More Lenient
Australia, Israel,
France
Israel
More Lenient
US, Canada
More Lenient
US
More Lenient
US
More Lenient
Australia, US
Stricter
Australia, France
More Lenient
The Netherlands,
Australia, UK
Australia
More Lenient
Average
Average
Spain, France
(excluding UK)
n/a
Average
n/a
Average
n/a
Average
n/a
110 West Nile Virus
Appropriate
Protects the
Patient
Protects the
Patient
Protects the
Patient
Average
Smallpox
Vaccine
Contact with
Blood
Lenient
Absent,
Lenient
Protects the
Patient
Average
Engaging in
Prostitution
Strict
Protects the
Patient
Stricter
Engaging in Sex
with a Prostitute
IV Drug Use
Strict
Stricter
Average
Japan
Sex with an IV
Drug User
Non-IV Drug Use
Strict
Protects the
Patient
Protects the
Patient
Protects the
Patient
Protects the
Patient
Austria, Belgium,
France,
Germany, Italy,
Spain
Australia, US,
Austria, Israel,
Canada, UK
Austria,
Germany, Spain,
France
Australia, France
New Sexual
Partners
Stricter
Piercing- sterile
environment
Appropriate
Protects the
Patient
More Lenient
Piercingunsterile or
unsure
environment
Strict
Protects the
Patient
Stricter
Tattoos- sterile
environment
Tattoos- unsterile
or unsure
environment
Appropriate
Protects the
Patient
Protects the
Patient
More Lenient
Jail
Strict
Protects the
Patient
Stricter
HIV Positive
Partner
Strict
Protects the
Patient
Stricter
MSM
Strict
Protects the
Patient
Stricter
Austria,
Germany, Spain
Australia, UK,
France, Italy,
Spain, US,
Switzerland
Austria, US,
Spain, The
Netherlands,
France
Austria, Belgium,
UK, France,
Germany, Italy,
Spain,
Switzerland
Spain, France,
US
Austria, Belgium,
UK, France,
Germany, Italy,
Spain,
Switzerland
All excluding
Australia,
Canada,
Germany, US
France,
Germany, Italy,
Spain
Italy, Spain
Strict
Strict
Absent,
Appropriate
Strict
Stricter
Stricter
Average
Stricter
US, Canada,
Israel
Spain
111 Females who
have sex with
MSM
HIV-O Exposuretravel
HIV-O Exposuresexual partner
Hepatitis
Infection- HCV
Hepatitis
Infection- HBV
Strict
Protects the
Patient
Stricter
Appropriate
Protects the
Patient
Protects the
Patient
Protects the
Patient
Protects the
Patient
More Lenient
Sweden, Spain,
Japan, Italy,
France
Germany
More Lenient
Germany
Average
Israel
Average
Hepatitis
Exposurecohabitation
Hepatitis
Exposure- sexual
partner
Antibiotics
Strict
Protects the
Patient
Stricter
Sweden,
Belgium,
Australia
Austria,
Germany, Spain
Strict
Protects the
Patient
Stricter
Appropriate
More Lenient
Recovery from
Infection
Use of Clotting
Factor
Concentrates
Sex with a
Hemophiliac
Sex with an
Individual that
uses Clotting
Factor
Concentrates
Temperature
Appropriate
Protects the
Patient
Protects the
Patient
Protects the
Patient
Appropriate
Lenient
Lenient
Strict
Strict
Strict
Appropriate
More Lenient
Austria,
Germany, Spain,
France
US, Spain,
Canada
Australia, US
Stricter
Italy, Austria
Protects the
Patient
Protects the
Patient
Stricter
Austria, UK,
France, Spain
Austria, UK,
France, Spain
Protects the
Patient
More Lenient
Stricter
Belgium, The
Netherlands,
Spain, Italy,
France
112 Summary of Classification of Comparison between US Policies, Scientific Data, and International Policies, Figure 34 Key for Figure 34 Key 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 Regulation Pulse Blood Pressure-­‐ Upper Limit Blood Pressure-­‐ Lower Limit Age-­‐ lower limit Age-­‐ upper limit Volume of Donation Frequency Weight Hemoglobin-­‐ Female Hemoglobin-­‐ Male Heart and Lung Problems Pregnancy Cancer Diabetes Malaria-­‐ Travel Malaria-­‐ Residence Malaria-­‐ Infection vCJD-­‐ travel CJD-­‐ family history vCJD and CJD-­‐ clinical exposure Chagas Disease Babesiosis West Nile Virus Contact with Blood New Sexual Partners Engaging in Prostitution Engaging in Sex with a Prostitute IV Drug Use Sex with an IV Drug User Non-­‐IV Drug Use Piercing-­‐ sterile environment Piercing-­‐ unsterile or unsure environment Tattoos-­‐ sterile environment Tattoos-­‐ unsterile or unsure environment Jail HIV Positive Partner MSM Females who have sex with MSM HIV-­‐O Exposure-­‐ travel n 9 8 8 15 15 13 15 15 10 10 12 15 13 10 15 11 11 13 15 15 15 15 11 14 10 13 12 15 12 14 15 15 15 15 12 13 15 15 8 40 41 42 43 44 45 46 47 48 49 50 HIV-­‐O Exposure-­‐ sexual partner Hepatitis Infection-­‐ HCV Hepatitis Infection-­‐ HBV Hepatitis Exposure-­‐ cohabitation Hepatitis Exposure-­‐ sexual partner Antibiotics Recovery from Infection Use of Clotting Factor Concentrates Sex with a Hemophiliac Sex with an Individual that uses Clotting Factor Concentrates Temperature 10 15 15 9 13 14 12 11 11 10 12 115 CHAPTER 6
Discussion
Large Discrepancies Between US Policies and Scientific Data
When comparing the US policies to current scientific data and available testing
capabilities many discrepancies are uncovered. The most glaring inconsistency is the difference
between deferral times and testing eclipse periods. There are specific groups that have been
identified as too high risk to consider allowing to donate. In these cases, it is simply because
allowing these groups to donate would not be cost-efficient, due to the large percentage of
blood that might have to be destroyed after testing positive for TTI. All populations included in
the lifetime deferral group should have a risk rate above a predetermined value. All populations
who fall below this value, but are still a safety concern, should be deferred for the maximum
eclipse period to ensure accurate tests.
Currently, the US has lifetime bans or temporary deferrals on populations whose risk
rate is lower than populations who have no deferrals. For example, the risk rate associated with
the use of clotting factor concentrates is insignificant compared to the increased risk of being a
young American male living in an urban area. A risk rate must be identified to define the cut off
risk rate between a deferral and no deferral, and the exact target of these deferral policies must
be decided. Currently, African American men are 8 times more likely to become infected with
HIV than their white counterparts. 1 in every 16 African American men, or 6.25% become
infected with HIV, making this population’s risk the highest allowed risk rate for a non-deferred
population. Straight males who have had a one time exposure via a HIV positive prostitute has a
risk rate of 0.04%. Between these two populations, African American males are not deferred. It
is clear policymakers would never create regulations determined by race, because it would be
based in discrimination and add another level of institutionalized racism. However, the lifetime
MSM deferral, which effects the majority of the male gay and bisexual community, are deferred
for having a sexual relationship with their partner. Even if an individual is in a monogamous
116 relationship, or uses protection, they are still subject to a lifetime deferral. Deferring someone
based on their race, and deferring someone based on their sexuality, are equally damaging to
public interest, and are both based in discrimination. If deferral policies are going to be
completely evidence-based, the risk rates must accurately define the level of acceptable risk,
and policies must abide by these ranges. It is up to policymakers to decide if public interest is
outweighed by public safety. If this is the case, it must be uniform throughout deferral policies,
no group of individuals should be singled out for something out of their control, like sexuality,
birthplace, and race.
Deferring straight males who have had a one time exposure to a prostitute, and MSM
has a lesser effect on the blood supply than deferring all African American males. Therefore, it
is understandable that these risk groups would be deferred to increase the safety of the blood
supply, even by a minute amount. However, if this is the case, the deferral period should reflect
the true risk of the exposure, and only defer for a maximum of 2 weeks after the event, if the
concern is HIV. Policymakers need to develop regulations which are reflective of current
scientific data and other policies put in place. Additionally, they need to balance public interest
and public safety in a fair, non-discriminatory way.
Large Discrepancies Between US Policies and International Policies
Overall, there are many overlapping policies, which indicate policies are either all a
reflection of the same current scientific data, or they are a reflection of each other. The later
possibility was seen in the prior analytical sections. For example, Canada looked to the UK for
data on pulse and its role in donor screening, and to the US for the analysis on age maximums.
There were several countries whose policies were very similar, suggesting these countries
share some contributing factor, like acceptable levels of risk, their view on social aspects of
policy making, or they integrate scientific data in similar ways.
When looking at countries’ leniency, clusters of countries seemed to share similar
policies. Canada, UK, Australia and the US shared many of the same lenient policies, the
117 majority of which addressed donor safety concerns, compared to the continental European
countries. Spain, France, Austria, and Italy were often found grouped together when they had
the most lenient policies, all of which assessed the risk of exposures that would put the patient
receiving the blood at risk. Every country had at least one policy which was the most lenient.
However, there were a few countries who, overall, were more lenient in the comparison. Only
two countries, Spain and France, had the most lenient policies for more than one third of the 50
policies included in the study. The majority of these lenient policies were for topics which were
meant to protect the patients receiving the blood. When looking at policies meant to protect the
donor, either Australia, the UK, or the US were the most lenient policy in all but one of the topics
covered in the study. Japan and Sweden had the least amount of lenient policies in the
comparison.
It is now important to look at the outcomes of these policies to understand the effect of
each county’s regulations, and the level of success their implementation has provided. First, to
look at the safety of the donors, the number of ADR can give information about the
organization’s ability to screen out high risk individuals and protect them from negative heath
outcomes. Australia reports 2.2% of donors experience ADR after donating blood. Italy’s READ
project, meant to record and monitor the number of ADR, concluded 0.69% of donors
experience an ADR.142 With so many different classifications and severities of ADR it is difficult
to make any conclusions from these risk rates. It is interesting, however, that Australia was one
of the most lenient countries regarding patient safety, especially in comparison to Italy, who
often had stricter policies for donors, but more lenient policies regarding risks for patients. This
suggests more stringent policies meant to protect the donor might have positive effects on the
rate of ADR.
The outcomes of the policies meant to protect the patients can be compared with the
number of infectious diseases transmitted through blood transfusions. Looking at countries that
used a 4 month deferral period for exposures to HCV, HBV and HIV, the rates of TTI in patients
118 were not uniformly higher than countries who used the 12 month deferral period. Using values
from a Eurosurveillance report, the rates for the several of the countries included in the study
can be compared. France, Germany, Spain, and Italy use a 4 month deferral period for the
majority of their exposure based deferrals. Their rates for HCV, the infection with the longest
eclipse period, were 0.1, 0.23, 2.33, and 0.5 per one million respectively.143 UK, Canada, and
the US had 12 month deferral periods for a majority of their exposure based deferral periods.
Their rates for HCV were 0.7, 0.72, and 1.3 per one million respectively.138,143,144
For all infection risk rates of HIV, HCV, and HBV, Spain was the major outlier, with
significantly higher rates compared to other countries with similar policies. This might be due to
a few common regulations missing from Spain’s blood collection organization’s policies, like the
lifetime deferral of MSM, which was a major source of HIV positive blood in the US before the
ban was implemented. France, Germany, and Italy all have a risk rate of at least half of the UK,
US and Canada. These findings suggest instating longer deferral periods will not increase the
safety of the blood system, however, the deferral periods themselves are imperative to a safe
blood system.
119 CHAPTER 7
Policy Recommendations
Overarching Questions for Policymakers: Important Factors for Consideration
Questions 1: Should blood donation incorporate public health screenings?
Some argue that screening blood donors is a public health service to inform high-risk
individuals of their infection status. However, it is important to differentiate between different
types of health based non-profit organizations. While blood collection agencies do inform
individuals if their blood tests positive for a type of infection, that is a service, not their primary
purpose. This is why ARC often states individuals should not donate blood if they are doing so
to get a blood test. This is an inefficient use of their resources and other public health
organizations can provide individuals with this service. The possibility of a public health aspect
should not be included in policy making for donor eligibility.
Question 2: Can you rely on the honesty of individuals in the blood screening process?
An incredibly important component of the blood collection process is dependence on
donor’s honesty. When discussing policies and regulations, the possibility of donors lying during
their health histories section inevitably comes up. However, the entire system to gauge
exposures is currently based on trusting the donors. Hypothetical populations of donors who
would lie about exposures to new policy suggestions, would have also lied with the current
system in place. These individuals cannot be controlled by specifically worded questionnaires
and the system must depend on the screening in place to identify any risks. Therefore, the
argument that donors might lie holds no clout and must not deter the efforts of policymakers.
Question 3: What type of deferrals are discriminatory?
Policymakers must make the decision about whether they want to defer populations
based on specific activities that put an individual at risk, or based on demographics and
absolute risk statistics, which can be discriminatory and harmful for the diversity, fairness, and
stability of the US blood supply. If the safety of the blood supply was the only priority, the FDA
might consider policies that ban African American and Hispanic men, because the absolute risk
of these populations is greater than the absolute risk for currently deferred populations.
However, policy makers would never use race to distinguish between who can and cannot
donate blood, as it creates a harmful stereotype and is based in discrimination. A lifetime
deferral for MSM and individuals born in Sub-Saharan Africa is also a form of discrimination.
Just as it would be ignorant and inappropriate to assume actions based on race, it would be the
same to assume actions based on sexual preference and place of birth. Instead, the high-risk
action itself should be deferred. The activity that puts MSM individuals at risk for HIV is
unprotected anal sex with a new partner. Therefore, unprotected anal sex with a new partner
should cause a deferral of at least 9 days if HIV is the only concern, or 4 months if HCV is also a
concern. Similarly, being in prison is not the activity that causes HCV infections, it is activities
that take place at a higher frequency within the prison that cause these infections, including
unprotected anal sex, sharing needles, and unsterile tattoo equipment. Discrimination based on
being part of a population with a high prevalence of TTI needs to be a cause for a deferral in all
cases, or in no cases. The inclusion of high risk demographic should not be cherry picked if
policies are going to reflect the gold standard in protection, avoid discrimination, and respect the
rights of individuals.
Policy Suggestions
High Risk Exposure Policy Suggestions
All questions should be focused around the transmission activity itself to reduce
confusion and increase specificity, which in hope, would cause the correct population to be
deferred and reduce the amount of healthy people turned away.
Conservative estimates put condom misuse, slipping, or breaking, at approximately 2%,
a statistic which is supported by the finding that condoms are 98% effective with perfect use.145
However, it is well known that perfect use is not universal. Researchers have found condoms
are 85% effective with “typical use,” leaving a 15% chance of failure for the general public using
121 condoms.146 Specifically in terms of HIV, scientific studies have found condoms are 100,000
times more effective at protecting an individuals from HIV then using no protection at all.147 If an
individual were to have protected sex with a completely random individual, someone whose
infection status is unknown, their risk for contracting HIV is miniscule.
There are countless different variables that can effect the likelihood of an individual
contracting HIV, including, but absolutely not limited to, gender, circumcision, likelihood of a
partner being HIV positive, the effectiveness of condoms, an HIV positive partner’s viral load,
when they became infected, and the type of protection an individual typically uses. If brought to
the most general level, accounting for gender, risk of condom malfunction, transmission risk,
and likelihood of a random sexual partner being HIV positive, assumed by the prevalence in the
US, 0.16%, the risk varies by type of sexual act, and ranges from a risk rate of 3.36 x 10-6 for
receptive protected anal sex to 9.6 x 10-8 for males involved in protected penetrative vaginal sex
(See appendix). Additionally, the higher risk activities affect a smaller percentage of the
population than the less risky activities. Over the course of a year, only 3.2% of men and 12.4%
of women 16 and over engage in anal sex as the receiving partner, compared to 60% of men
and 57.5% of women 16 and over who engage in vaginal sex.148 This suggests any type of
condom protected sex should not lead to a deferral if the worry is exposure to HIV, which is the
case specifically for MSM.
Policies to protect the patient are in place to account for the eclipse period following
infection, which historically, has been the source of most TTI that are screened for. The main
infections of concern are HCV, HBV, and HIV. Hepatitis viruses are becoming increasingly less
concerning now that HCV is curable and HBV is preventable with a vaccination. HBV can now
be avoided if all recipients of blood transfusions received a vaccine directly before or after they
are exposed to the donated blood. There has been a major push to increase HBV vaccinations,
due to the chronic, and therefore expensive, nature of the disease. Including HBV vaccines
when individuals receive blood transfusions will not only eradicate the possibility of subsequent
122 HBV infections, but it will also increase the percentage of the population receiving the vaccine.
Unfortunately, HCV does not have a vaccine, however, very successful treatments have
recently become available, reducing some of the potential long term destruction a blood
transfusion might have on an individual. In comparison, HIV has no cure nor any type of
vaccine. However, out of the three TTI, HIV’s eclipse period is the shortest, lasting only 9 days.
While all infections, regardless of how preventable or treatable they are, should receive the
same amount of robust attention, knowing that research and clinical care is improving to reduce
the effects of possible TTI should encourage policy makers to continue to be open to new
scientific breakthroughs which reduce the possible negative effects of transfusions. So far,
synthetic human blood has eluded researchers, but other avenue to increase the supply of
blood is to increase eligibility by eliminating transmission risks in other ways.
Pending further breakthroughs, the deferral period should still reflect the longest
common TTI eclipse period, which can be up to 3 months for HCV infections. While not
necessarily scientifically warranted, “buffer time” is important to reduce the amount of donors
who might be mistaken about how long ago the exposure was. If the exposure was a week early
then they remember, it might be a significant problem if the deferral period is set at 3 months.
However, if it is set at 4 months, there is room for human error. To make policies reflect the
screening capabilities, HIV and Hepatitis exposures should be separated into three distinct
groups: exposures that warrant no deferral, exposures which cause a 4 month deferral, and
exposures which cause a lifetime ban.
Suggested Wording for Health Histories Questionnaire:
• In the past 2 weeks (14 days) have you had sex with an individual who is/ was at high
risk* for being HIV positive?
* “High Risk” Includes:
§ An individual who partakes in unprotected anal sex
§ An individual who shares needles
§ An individual who has frequent unprotected sex with multiple partners
§ An individual who lived in or was born in Sub-Saharan Africa (if proper
FDA approved blood tests are not used)
123 •
In the past 4 months, have you lived with, or had sex with, an individual who was a
chronic carrier of viral hepatitis*?
* Hepatitis A, B, C, or E Virus, CMV, other unknown forms of viral jaundice and hepatitis
•
Have you ever shared a needle* with another individual, even with a family member or
someone you believe to be infection free?
* Often, shared needles are used to inject drugs and to receive tattoos or piercings
•
Have you been incarcerated (juvenile detention, prison, lock-up, jail) in the past 4
months?
o
If yes thanà while you were incarcerated, did you ever engage in any activities
that would put you at a higher risk* for contracting the Hepatitis C Virus?
* “High Risk” Includes anything that would have exposed you to another
individuals bodily fluids, including, but not limited to:
• engaging in anal intercourse
• sharing of needles
• receiving a tattoo or piercing
• an accidental needle stick
• or a violent interaction with another inmate.
* You do not need to disclose any more information other than confirming an
exposure, you will not be asked any further questions on said topics
•
It would benefit everyone to have the exact date of the last day before an individual must
be exposure free for each risk. For example, when organizations provide computers for
donors to answer the health history questionnaire, having the exact date of “4 months
ago” printed below each question with a deferral policy of 4 months on the screen will
allow for greater accuracy.
vCJD Deferral Policy Analysis
It is estimated that deferrals due to CJD and vCJD caused ARC to loose nearly 100,000
donors between 2001 and 2006.52 In every 1000 presenting donors in the US, 2.49 will be
deferred for travel restrictions related to vCJD.52 If the travel ban were lifted, the maximum risk
of vCJD entering the blood supply is 1.2 in one million, but the change in regulation would
increase the donor population by nearly 23,000. The risk becomes substantial when you factor
in the number of average blood donations per year for each donor and the maximum amount of
blood products that can be manufactured from a single donation. Lifting the travel ban would
potentially expose nearly 60 people to vCJD infected blood per year (see Appendix). This is far
124 too large of a risk to the blood supply, despite the additional 116,000 blood products that it
would bring. Therefore the current vCJD travel restrictions should be kept in place.
One beneficial aspect of this regulation is that, due to the limited time range, it will
become irrelevant within the next 20 to 30 years, when all individuals who lived in the UK during
the epidemic will no longer be donating. The more time that passes, the less the blood supply
will be effected by the travel restriction. Within 10 years, all individuals under 45 will be able to
donate despite having lived in Britain during their lifetime. Donors 45 and younger make up over
half of the blood supply, reducing the effect of the vCJD related regulations drastically.65
Protection of Donors Policy Suggestion
There are a few US policies in place to protect the donor that are scientifically
unwarranted and just reduce the number of eligible donors. Pulse is an example of these types
of policies. The UK has not used pulse for over 6 years and has not been met with a significant
increase in ADR. The current hemoglobin minimum level for women is the second area of
unnecessary stringency. The policy does not currently reflect the healthy ranges of hemoglobin
levels for the different genders, potentially putting some males at risk, and deferring healthy
females. Overall, the stricter areas do not compensate for the degree of leniency towards
donors’ health. It is well understood that donors who experience ADR are less likely to return to
donate again, by reducing the number of ADR overall, the US will be preserving the future of
their donor population, in addition to their current donors’ health.
The most serious area of leniency concerns the long-term health of donors. Frequent
donations reduce donor’s iron stores, potentially causing IDA. This is especially prevalent in
women of childbearing age, who’s iron levels already fluctuate constantly. Areas that could that
address the sustainability of hemoglobin and iron levels in donors would be a change in the
allowed frequency of donations, a higher minimum hemoglobin levels, and a lower volume of
donation. EBV can also be included as a contributing factor to identifying the maximum volume
of blood that can be safely removed from a donor. The majority of countries vary the volume of
125 blood collected based on the donor’s EBV. This customized collection procedure increases the
efficiency of the system while simultaneously protecting the donors in the highest possible
capacity. Varying the collection volume has not greatly reduced other countries’ overall
collections because donors with larger EBV donate a larger volume that compensates for the
donors who donate a slightly smaller volume. Additionally, the donors who would have
experienced an ADR if more blood was removed do not have this experience, and are therefore
more likely to continue donating, further preserving the future blood supply. The volume the
CFR allows for collection does not agree with the evidence-based calculation of the amount of
blood that can be safely removed from the body, greatly increasing the likelihood of donors
experiencing an ADR.
Further leniency is seen when looking at the difference in policies concerning donations
after recovery from cancer, heart and lung problems, pregnancy, and diabetes. In all of these
situations, adequate scientific data was not available to back up possible policy options, and the
US was forced to make decisions based on advice from collection organizations, the Blood
Products Advisory Committee, and policymakers’ judgment. In these cases, the level of
precaution each country chooses to take for their donors can be viewed, because their
acceptable risk is the main driving factor for these policies, not scientific data. For these 4
topics, the US is either equal to, or more lenient than, the most lenient country in the
international cohort. The international countries included in the study created significantly more
cautious policies in response to the lack of scientific data compared to the US. Overall, in
comparison to both scientific data and international collection agencies, the US policies
regarding donor safety are lenient and potentially put donors’ health at risk to increase the
eligible population in the short term.
Travel Regulations for Malaria Policy Suggestions
Malaria regulations should be consistently updated to reflect the riskiest areas for
Americans to travel and exclude any low risk regions, which are a major source of deferrals.
126 Deferrals based on travel to Mexico should not be equivalent to travel to Africa. Using the
statistics and risk rates addressed in a previous chapter, reducing the deferral period for travel
to low risk ME areas, like Mexico, the Caribbean, and Central America, from 12 months to 3
months, would increase the blood supply by 60,745 donations per year (Calculations in
Appendix). This increase in donations is not just due to the reduced deferral period itself, but
also the reduction of people who experience a deferral, who are statistically less likely to return
to donate again even once they are eligible. The calculated total risk of 0.06 infections per
million transfusions is only increased by one additional infectious unit entering the blood supply
every 57 years. The outcome of this policy change would an additional 3.5 million donations for
each additional malaria infected unit introduced into the blood supply, making it a very attractive
area for policymakers to address to increase the eligible population.
127 Limitations
This study collected data from 15 countries, including the US, which spanned nearly 10
different languages. The language barrier was extremely difficult to overcome. The majority of
translations were done online, using secondary sites to confirm the first sites translations. When
translations did not match, native or fluent speakers were contacted to aid in translation.
Possible misunderstandings during translation may have led to some discrepancies between
the study data and the true policy. Additionally, some countries did not have data available for
all policies addressed, these situations are marked in grey in the data found in the appendix.
This missing data might have effected the international average, biasing the results.
Other limitations include possible inconsistencies between statistics. For studies looking
at deferral rates, risk rates, and demographics, values might have slightly differed based on the
time of publication and the study population. In attempt to control for these situations, the values
calculated using a research setting which most closely mimicked the topic in discussion was
used. However, the generalizability of the values may have been pushed past the researchers’
intended limits. This limitation may also be seen when comparing TTI transmission rates
between the countries. Data were limited for viral TTI rates for all countries and the surveillance
time of many of the studies varied, limiting the effectiveness of comparison. The values
calculated in this study are meant to give a general idea of the scope of the risk associated with
an increase in the blood supply. They are not meant to be exact calculations which perfectly
represent the true outcome of a policy change, just the magnitude and direction of the change
according to scientific data.
Finally, the topics included in the study and the summaries included with each section
are not meant to be an exhaustive list of all possible reasons an individual can be deferred.
Medications and clinical treatments were not included in the study because those policies often
differ between collection sites and are not nationally implemented. The material included in each
128 section is meant to provide the reader with the crucial information to look at the current policies
in a critical way, they are by no means a complete summary of the policy history of each topic.
Future Studies
An interesting area of further study would be the donor’s perception of his or her own
safety. Some donors believe donating blood should imply consent and the risk of consequential
ADR are the choice of the donor, because it is their body. When speaking with donors, there
were many who had experienced ADR, and still continued to donate. I myself have severe panic
attacks when donating blood. However, like many other donors, I feel that 10 minutes of being
uncomfortable should never outweigh the possibility of saving an individual’s life. Furthermore,
some donors feel as though it is their personal right to decide whether they are healthy enough
to donate. Viewpoints of FTD, RD, and non-donors would provide interesting insight about the
purpose, perception, and opinions donors have about regulations pertaining to their own safety.
Additionally, looking at the way in which the public’s perception of safety is reflected in the
policies as they are reassessed would give valuable information about the policy climate
surrounding blood collection regulations.
This study generally looked at many different policies in comparison to scientific data
and international collection organizations. It highlighted important areas to look to improve the
US blood supply. Future studies would benefit from looking at individual policies in an intensely
critical way to provide the necessary data to encourage policy change.
Conclusion
There is significant variation seen across international blood collection organizations.
Countries who prioritize donor safety tended to have more lenient policies concerning patient
safety, and vice versa. In many cases, topics which had very strong scientific data available had
less variation between countries, regardless of their preference towards donor or patient safety.
To increase the quantity and safety of the US blood supply, reducing deferral periods for TTI
exposures to a length of time which reflects the eclipse period of blood tests will significantly
129 increase the blood supply, without changing the level of safety for patients receiving the blood.
Additionally, making regulations concerning donor safety more conservative may aid in the
reduction of ADR and long-term negative health outcomes, and preserve the future blood donor
population. The current US system has historically been able to meet the demand for blood.
However, as the demand for blood increases at a faster rate than the growth of the donor
population, the national supply will quickly become depleted, making the current system
unsustainable. Policy changes to increase the size and stability of the donor population is the
solution to address potentially detrimental effects of a blood shortage.
130 Appendix
I) Top 50 Countries on the Human Development Index
II) Top 30 Countries for Healthcare Spending per Capita
III) History of Transfusions
IV) Non-Infectious Transfusion Complications: Rates, Symptoms, Treatment and Prevention
V) International Comparison Raw Data
VI) Additional Figures and Graphs
VII) Calculations
VIII) Prevalence of Deferral Characteristics in America’s Adult Population
IIX) Glossary of Common Acronyms
IX) Donor Health Questionnaire
X) Center for Disease Control and Prevention Malaria Exposure Traveler Map
131 I) Top 50 Countries on the Human Development Index 49
1. Norway
2. Australia
3. Switzerland
4. Netherlands
5. United States
6. Germany
7. New Zealand
8. Canada
9. Singapore
10. Denmark
11. Ireland
12. Sweden
13. Iceland
14. United Kingdom
15. Hong Kong, China (SAR)
16. Korea (Republic of)
17. Japan
18. Liechtenstein
19. Israel
20. France
21. Austria
22. Belgium
23. Luxembourg
24. Finland
25. Slovenia
26. Italy
27. Spain
28. Czech Republic
29. Greece
30. Brunei Darussalam
31. Qatar
32. Cyprus
33. Estonia
34. Saudi Arabia
35. Lithuania
36. Poland
37. Andorra
38. Slovakia
39. Malta
40. United Arab Emirates
41. Chile
42. Portugal
43. Hungary
44. Bahrain
45. Cuba
46. Kuwait
47. Croatia
48. Latvia
49. Argentina
50. Uruguay
132 II) Top 30 Countries for Healthcare Spending per Capita 50
1. Norway
2. Switzerland
3. United
States
4. Luxembourg
5. Monaco
6. Denmark
7. Australia
8. Canada 9. Netherlands 10. Austria
11. Sweden
12. Japan
13. Belgium
14. France
15. Germany
16. Finland
17. Iceland
18. San Marino
19. Ireland
20. United
Kingdom
21. New
Zealand
22. Andorra
23. Italy
24. Spain
25. Singapore
26. Israel
27. Greece
28. Qatar
29. Cyprus
30. Slovenia 133 III) History of Transfusions
1628- William Harvey describes the circulatory nature of blood within the body.149
1657- Christopher Wren conducts experiments where he injects different fluids into the
veins of animals.149
1665- Richard Lower conducts the first successful blood transfusion between dogs.150
June 1667- Jean-Baptiste Denis conducted the first ever animal to human blood
transfusion in Paris. He theorized about the use of the procedure, to not only correct
blood loss, but also to treat diseases.149
November 1667- Lower and Edmund King carry out the first animal to human blood
transfusion in England. The subsequent events of both the English and Parisian patients
deaths led to a ban of blood transfusions in Paris and England. Blood transfusions were
not revisited again for 148 years.149
1816- John Henry Leacock publishes his dissertation which argued that both parties in a
blood transfusion must be of the same species to be successful.149
1828- Inspired by Leacock’s research, obstetrician James Blundell brought blood
transfusions back into clinical practice by using the technique to treat post-partum
hemorrhaging.149
1840- Samuel Armstrong Lane carries out the first successful blood transfusion to treat
hemophilia with help from Blundell.150
1853-1864- Blundell, Alexander Wood, Joseph Roussel, and James Aveling all
participated in the development of new blood transfusion devices. One limitation for
treatments was the inclination for the blood to clot during the transfusion. Thomas Smith
and James Braxton-Hicks each developed their own methods of addressing this
challenge.149
1873-1880- American doctors infuse milk as a “blood substitute,” it has very limited
successes. Saline infusions replace milk in 1884.150
1901- Karl Landsteiner discovers three different blood types, A, B and O. Alfred von
Decastello and Adriano Sturli identifies the forth, AB, a year later.149
1914-1915- Belgian Adolph Hustin, Argentinian Luis Agote, and American Richard
Lewisohn all contribute to developing the correct concentration of sodium citrate, which
could be added to blood to inhibit clotting without harming the patient.149
1918- The first blood bank is established by Osward Robertson. He was the first to
discovery the benefits of adding glucose to the blood to preserve its integrity.149
1933- Lewisohn and Nathan Rosenthal collect data on the implications of using unsterile
equipment during the transfusion process. They were the first to describe transfusionassociated infections.149
134 1937- The first large-scale blood storage center is established in response to the
Spanish Civil War.149
1939- London’s Army Blood Transfusion Service establishes the Army Blood Supply
Depot (ABSD). In its first year, ABSD processes over 33,000 donations.149
1940- Landsteiner, continuing his research for 40 years, concludes his career with the
discovery of the Rh blood group alongside Alexander Wiener.149
1947- The American Association of Blood Banks, now known as AABB, is formed. They
publish the first edition of TRANSFUSION in 1960.150
1959- Max Perutz decodes the molecular structure of hemoglobin.150
1970- The voluntary blood donor system begins to be transitioned into blood banks. This
replaces the old system of compensating donors for their blood.150
1971- Hepatitis B testing is introduced into the panel of blood tests conducted on
transfusion units. An additional Hepatitis B test in added in 1987 followed by the
Hepatitis C test in 1990.150
1981- The first case of AIDS is reported. HIV is not identified as the precursor virus until
3 years later. The first blood test for HIV is developed in 1985 and is immediately
implemented into the blood test panel.150
1999- Nucleic Acid Amplification Testing (NAT) begins to be introduced into blood banks
on a trial bases until its license by the FDA in 2002. NAT is now the primary testing
procedure used.150
135 IV) Non-Infectious Transfusion Complications: Rates, Symptoms, Treatment and
Prevention
Complication
Rate
Symptoms
Treatment
Prevention
Febrile
transfusion
reactions
1: 330 RBC
transfusions
and 1: 20
platelet
transfusions
Chills, rigor, discomfort, 1OC
drop in body temperature
within 3 hours of transfusion
(not due to sepsis or hemolytic
reaction)
General supportive
care, antipruritic
therapy if necessary
Leukoreduction of RBC
units
Transfusionassociated
circulatory
overload
(TACO)
1-10% of
transfusions
Dyspnea, tachypnea, jugular
venous distention, elevated
systolic blood pressure,
hydrostatic pulmonary edema
that improves rapidly
Diuresis
Slow transfusion rate,
identification of high risk
patients (critically ill,
infants, those with
cardiac or renal
diseases), diuretics
Transfusionrelated acute
lung injury
(TRALI)
1: 5,000
transfusions,
high
morbidity and
mortality
rates,
accounted for
30% of the
transfusion
related
deaths in the
US in 2009
Non-cardiogenic pulmonary
edema within 6 hours of
transfusion which does not
improve rapidly (the diagnostic
difference between TACO and
TALI), lung injury, life
threatening
Supportive care,
heavy reliance on
prevention
Plasma mitigation,
limiting transfusions if
possible
Allergic
reactions- Mild
1-3% of
transfusions
Localized erythema, pruritus,
hives, urticarial reactions
Parenteral
antihistamines
Concentrating and
washing platelets for
platelet transfusions
Anaphylactic/
Anaphylactoid
transfusion
reaction- severe
allergic reaction
1: 50,000
Bronchospasm, stridor,
hypotension, gastrointestinal
symptoms, life threatening
Epinephrine
Concentrating and
washing platelets for
platelet transfusions
Acute hemolytic
transfusion
reactions
(AHTR)
1:12,0001:100,000
Sudden onset, within 24 hours
of transfusion, fever, chills,
facial flushing, pain,
hypotension, dyspnea, renal
failure, disseminated
intravascular, high mortality
rate
Monitoring in the
ICU, supportive care
Improving blood bank
safety, usually due to
mistyping or labeling of
blood leading to an
incompatible ABO type
transfusion
Delayed
hemolytic
1: 1,900
Usually less severe than acute
version, fever, reduced urine
Supportive care,
transfusion of
Improving blood bank
safety, usually due to
136 transfusion
reactions
output, often asymptomatic but
diagnosed due to unexplained
drop in hemoglobin
concentration
appropriately typed
blood, intravenous
immunoglobulin and
steroid therapy if
necessary
mistyping or labeling of
blood leading to an
incompatible ABO type
transfusion
Posttransfusion
purpura
Rare, occurs
in 1:50,000 to
1:100,000
transfusions
Purpura, epistaxis,
gastrointestinal bleeding,
thrombocytopenia, all
observed five to ten days after
transfusion
Intravenous
immunoglobulin
Clear medical history to
avoid transfusing units
with anti- platelet antigen
in patients with a history
of post-transfusion
purpura
Hypotensive
transfusionreaction
Between 1
and 2 per
1,000
transfusions
Rapid drop in systolic blood
pressure
In most cases,
responds
immediately to
cessation of
transfusion
No preventative
measures, but very
treatable complication
Transfusionassociated
graft- versushost disease
Fatal in 84%
of cases
Fever, liver dysfunction, rash,
diarrhea, pancytopenia
Very poor outcome
with treatment, focus
on prevention
Leukocyte reduction and
irradiation of units
intended for high risk
patients, especially
severely immunecompromised patients
Sources: Gilliss BM, Looney MR, Gropper MA. Anesthesiology. 2011;115:635-649. Sarode R. Merck. 2014:1-12. Ibojie J, Greiss M a., Urbaniak SJ. Transfus
Med. 2002;12(3):181-185. Tobian AAR, Savage WJ, Tisch DJ, Thoman S, King KE, Ness PM. Transfusion. 2011;51:1676-1683. Faed J. NZBlood. 2014:1-8.
Shtalrid M, Shvidel L, Vorst E, Weinmann EE, Berrebi A, Sigler E. Isr Med Assoc J. 2006;8:672-674. Blood Safety Basics. Centers Dis Control Prev Natl Cent
Emerg Zoonotic Infect Dis. 2013.
137 V) International Comparison Raw Data Vitals
Allowed Blood
Pressure Range
Allowed
Pulse
Range
Australia
Austria
Belgium
Canada
Systolic 180-100 mmHg
Diastolic 100-50 mmHg
50-100 bpm
Systolic 180-90 mmHg
Diastolic 100-50 mmHg
50-100 bpm,
unless very
athletic
None
England and
North Wales
France
None
Germany
Systolic 180-100 mmHg
Diastolic =/<100 mmHg
Israel
Systolic 180-100 mmHg
Diastolic 100-60 mmHg
Systolic 180-100 mmHg
Diastolic 110-60 mmHg
Italy
Japan
Systolic >/= 90 mmHg
Diastolic- none
Spain
Systolic 180-90 mmHg
Diastolic 100-50 mmHg
Sweden
Systolic </=180 mmHg
Diastolic </=100 mmHg
Switzerland
The
Netherlands
United States
Whole Blood
Donation Age
Regulations
Australia
Austria
Belgium
Canada
England and
50-110 bpm,
unless very
athletic
50-100 bpm
Allowed Hb Range for Whole
Blood
Female 12-16.5 g/dL
Male 13-18.5 g/dL
Female >/= 12.5 g/dL
Male >/= 13.5 g/dL
>/= 12.5 g/dL
Female 12.5-16.5 g/dL
Male 13.5-18 g/dL
Female >/= 12 g/dL
Male >/= 13 g/dL
Female >/= 12.5 g/dL
Male >/= 13.5 g/dL
>/= 12 g/dL
50-100 bpm,
unless very
athletic
50-100 bpm,
unless very
athletic
200 mL- >/= 12.5 g/dL for
male, >/= 12 g/dL for female
400 mL- >/= 13 g/dL for male,
>/= 12.5 g/dL for female
Female 12.5 -15.5 g/dL
Male 13.5 - 18.5 g/dL
50-110 bpm
Systolic 180-80 mmHg
Diastolic 100-50 mmHg
First Time Donors
Minimum
16 with parental consent
in some regions, 17 in
remaining
18
18
17
17
50-100 bpm
>/= 12.5 g/dL
First Time
Donors
Maximum
71
Repeat Donor Maximum
60
65
61
65
None
70
71 with MDs approval
70
81
138 North Wales
France
Germany
Israel
Italy
Japan
Spain
18
18
17 with parental consent
18
200 mL- 16
400 mL- 17 for males,
18 for females
18
Sweden
18
60- 65, need
MD approval
for new
donors
65
Switzerland
The
Netherlands
United States
18
18
60
65
Frequency of
Donation
Australia
Austria
Belgium
Canada
England and
North Wales
France
Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
Australia
Austria
Belgium
Canada
England and
65
65
60
60
60
16 with parental consent None
in some states, 17 in
remaining
Maximum Frequency of Whole
Blood Donations for Women
Under 18- 1 donation/yr
Over 18- 84 days
56 days, 4-5 donations/yr
56 days, 4 donations/yr
56 days
112 days
56 days, 4 donations/yr
56 days, 4 donations/yr
84 days
90 days, 2 donations/yr
200 mL- 28 days, 4 donations/yr
400 mL- 112 days, 2 donations/yr
Max total volume donated- 800 mL
70 with MDs approval
72
65 with MDs approval
65
69, 65 and older must have
donated at least once between
60 and 65
65 -70 with yearly MD
approval
Site dependent
65, 70, or no limit
75
70
None
Maximum Frequency of Whole
Blood Donations for Men
Under 18- 1 donations/yr
Over 18- 84 days
56 days, 6 donations/yr
56 days, 4 donations/yr
56 days
84 days, 4 donations/yr
60 days, 3 donations/yr
56 days, 6 donations/yr
56 days, 6 donations/yr
84 days
90 days, 4 donations/yr
200 mL- 28 days, 4 donations/yr
400 mL- 84 days, 3 donations/yr
Max total volume donated - 1,200
mL
60 days, 4 donations/yr
84 days, 3 donations/yr
3 donations/yr
84 days, 4 donations/yr
5 donations/yr
56 days
56 days
Volume of Whole Blood Donation
500 mL
450 mL- 500 mL
400 mL -480 mL
470 mL
139 North Wales
France
400 mL- 500 mL, average 470 mL
Germany
Israel
450 mL +/- 10%
Italy
450 mL +/- 10%
Japan
200 mL or 400 mL
Spain
450 mL +/- 50 mL
Sweden
450 mL
Switzerland
450 mL
The
Up to 500 mL
Netherlands
United States
500 mL + ~35 mL for screening
Weight Requirements for
Sliding Weight Scale
Whole Blood Donations
for Younger Donors
Australia
no
Austria
no
Belgium
Canada
England and North Wales
France
Germany
Israel
Italy
Japan
no
yes, sliding scale for all
donors under 23
yes, sliding scale for
female donors
between 17 and 20
no
no
no
no
no
Spain
no
Sweden
no
Switzerland
no
The Netherlands
no
United States
no
Pregnancy
Deferral After
Deferrals
Childbirth
Donation While
Breastfeeding
Australia
9 months
no
Austria
6 months
no
Belgium
Canada
England and
North Wales
6 months
6 months
6 months
yes
Minimum Weight for Donors
18 and Over
50 kg, (110 lbs.)
50 kg, (110 lbs.) and BMI over
19
50 kg, (110 lbs.)
50 kg, (110 lbs.)
50 kg, (110 lbs.)
50 kg, (110 lbs.)
50 kg, (110 lbs.)
50 kg, (110 lbs.)
50 kg, (110 lbs.)
200 mL- males 45 kg, females
40 kg
400 mL- 50 kg
50 kg, (110 lbs.)
50 kg, (110 lbs.)
50 kg, (110 lbs.)
50 kg, (110 lbs.)
50 kg, (110 lbs.)
Deferral After Pregnancy
Loss (Spontaneous or
Abortion)
Before 28 weeks- 6 month
After 28 weeks- 9 month
Before 12 weeks- 4 weeks
After 12 weeks- 6 months
6 months
6 weeks
Before 12 weeks- no deferral if
there was no significant blood
loss and it has been a week
since last dose of termination
pill, if taken
140 After 12 weeks- 6 months
6 months
France
Germany
Israel
Italy
6 months
6 months
6 months
12 months
no
yes
Japan
Spain
6 months
6 months
no
yes
Sweden
9 months
Switzerland
The
Netherlands
United States
Cancer
12 months
6 months
6 months
Australia
Austria
6 weeks
Deferral After
Recovery from
Malignant
Cancer
5 years
Lifetime
yes
Deferral After
Recovery from
Non Malignant
Caner
5 years
Malicious,
superficial or
mucosal lesion
allowed
Belgium
Canada
Lifetime
Non-melanoma
skin cancer and
in situ cervical
cancer allowed
Basal cell
carcinoma
allowed after 2
year deferral
England and
North Wales
Lifetime
France
Germany
Lifetime
Lifetime if chemo
is used
Israel
Italy
Japan
Spain
Lifetime
Lifetime
Lifetime
Lifetime
6 weeks
Miscarriage- 6 months
Termination-1 year
6 months
Before 12 weeks- length of
pregnancy before loss
After 12 weeks-6 months
Termination (mechanical)- 6
months
Termination (drug induced) or
Spontaneous loss- length of
pregnancy has there been no
loss
Allowed as long
as chemo has not
been used
Allowed
Allowed
Allowed
Localized tumor
which has been
removed and
individual has
completely
Deferral After Recovery from
Blood and Bone Cancers
Lifetime
Lifetime
Lifetime
Lifetime
Lifetime
Lifetime
Lifetime
Lifetime
Lifetime
Lifetime
141 recovered, in situ
cervical cancer,
basal-cell
carcinoma,
childhood (before
5) neuroblastoma
all allowed
Some in situ
allowed
Sweden
Lifetime
Switzerland
The
Netherlands
Lifetime
United States
12 months
Heart Attack
Australia
Deferral After
Recovery From
Heart Attack
Lifetime
Austria
Lifetime
Lifetime
Allowed if
asymptomatic
Lifetime
Allowed if
asymptomatic
Lifetime
France
Lifetime
Lifetime
Germany
Israel
Lifetime
Lifetime
Italy
Japan
Spain
Lifetime
Lifetime
Lifetime
Lifetime
Sweden
Lifetime
Belgium
Canada
England and
North Wales
Basalioma and
some cervical
cancer allowed,
all other skin
cancers lifetime
deferral
Allowed for low
risk in situ
cancers
Deferral After
Recovery From
Stroke
Lifetime
Lifetime
Lifetime
Diseases and Conditions that
Would Cause Deferral
Lifetime- Coronary artery
disease
12 months- chest pain, angina
Lifetime- Heart Failure, Cardiac
Arrhythmia, Circulatory
Disorders, Thrombosis
Lifetime- Coronary artery
disease
Lifetime- TIA, Heart Disease,
Heart Failure, Aneurysm,
Cardiomyopathy
12 months- Myocarditis
Lifetime- Heart Disease,
Valvular Disease, Angina
Lifetime- all heart problems
excluding corrected congenital
malformations and mitral valve
prolapse
Lifetime- Heart Disease
Lifetime- Heart Disease
Lifetime- all serious heart
conditions and heart diseases
excluding corrected congenital
malformations
Lifetime- Chest pain, Heart
disease, Heart failure, Cardiac
142 surgery, COPD, Pacemaker
Switzerland
The
Netherlands
United States
Diabetic Donors
Australia
Austria
Belgium
Canada
England and
North Wales
France
Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The Netherlands
United States
Malaria
Deferrals
Australia
Austria
Belgium
Canada
England and
North Wales
France
Germany
Israel
Italy
Lifetime
Lifetime
Lifetime- Pacemaker
2 weeks- COPD
6 symptom free months
6 months
Type 1
Type
Yes (if well regulated and have never used bovine insulin)
No
Yes (if controlled by diet only, well regulated, and
not taking any medications)
No
No
Yes (if well regulated and have not used insulin in 1
month)
Yes (if controlled by diet only or same medication
for at least 4 weeks, have not used insulin in 1
month, must not suffer from any diabetic related
complications- ulcers, heart failure, amputation,
etc.)
No
No
No
Yes (if insulin is not used)
Yes (if insulin is not used)
Yes (if insulin is not used)
No
Yes (if insulin is not used)
No
Yes (if well regulated)
Yes (never used bovine insulin)
Deferral after Return
Deferral if Born or
from Travel to
Lived in Endemic
Endemic Area
Area (qualify as
“lived in”)
Plasma- 4 months, 3
Plasma- 6 months
years for Papua New
Whole Blood- 6
Guinae
months and blood
Whole Blood- 4 months test
and blood test, 3 years
and blood test for
Papua New Guinae
6 months
Lifetime (3 years)
6 months
12 months
3 years (6 months)
6 months
Plasma- no wait
Whole Blood- 4 months
6 months
12 months
Plasma- 6 months
6 months
Deferral after
Recovery from
Malaria Infection
Plasma- 6 months
Whole Blood- 6
months and blood test
Lifetime
Plasma- 6 months
Whole Blood- Lifetime
3 years
3 years
4 years (6 months)
3 years
4 years
3 years
143 Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
WNV Exposure
Australia
Austria
Belgium
Canada
England and
North Wales
France
Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
Exposures
Australia
Austria
Belgium
Canada
Whole Blood- 3 years
1 year unless tested
negative
6 months
6 months
6 months
Plasma- 1 month
Whole Blood- 6 months
(minimum 4 week wait
for any travel outside
Europe)
12 months
3 year unless tested
negative
3 year (6 months)
including after
temporary return
trips
3 years (5 years)
Plasma- No wait
Whole Blood- 3
years (6 months),
unless tested after 4
months
3 year (6 months)
including after
temporary return
trips before 3 year
period is up, after 3
years, 12 months
Lifetime
3 years
3 years
3 years
Deferral After Travel to WNV Endemic Area
Plasma- No wait
Whole Blood- 4 weeks
4 weeks
No wait
4 weeks, if donor felt unwell during 4 weeks, deferred for 14 days after
full recovery or 7 days after completion of antibiotics (which ever is
longer), if infected 4 months after recovery
4 weeks
4 weeks
No wait
4 weeks
4 weeks, if infected 6 months after recovery
4 weeks, if infected 4 months after recovery
No wait, if infected 4 months after initial symptoms or diagnosis, which
ever was later
Deferral After
Deferral After Male
Deferral After Female
Engaging in Sexual
Exposure due to MSM
Exposure due to
Activities an HIV
Partner who is a
Positive Individual
MSM
12 months
12 months
12 months
Lifetime
4 months
4 months
12 months
Lifetime if since 1977
12 months
Lifetime
5 years
12 months
144 England and
North Wales
France
Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United
States
Exposures
Australia
Austria
Belgium
Canada
England and
North Wales
France
Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
Exposures
Australia
Austria
Belgium
Canada
England and
North Wales
France
Germany
12 months
12 months
12 months
4 months
4 months
Lifetime
Lifetime
Lifetime if since 1977
None
6 months
None
None
4 months
12 months
None
None
None
12 months
Lifetime
Lifetime
None
12 months
12 months
Lifetime
12 months
4 months
6 months
4 months if using
NAT, otherwise 6
months
12 months
12 months
12 months
12 months
Deferral After Engaging in
Sexual Activities with a
Prostitute
12 months
4 months
12 months
12 months
12 months
Deferral After Engaging in
Prostitution or Receiving
Compensation for Sex
12 months
Lifetime
Lifetime if after 1977
Lifetime if after 1977
Lifetime
None
4 months
None
Lifetime
Lifetime
Lifetime
Lifetime
4 months if using NAT,
otherwise 6 months
Lifetime
12 months
12 months
Lifetime
Lifetime
12 months
Deferral After New Sexual
Partner or Multiple Partners
None
None
4 months for new partner, 12
months for multiple partners or
group sex
None
None
Lifetime if after 1997
Deferral After Contact with Other’s
Blood
6 months
4 months
4 months
4 months
4 months if they have any kind
4 months
4 months
6 months
12 months
145 Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
Exposures
Australia
Austria
Belgium
Canada
England and
North Wales
France
Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
Exposures
Australia
Austria
Belgium
Canada
England and
North Wales
France
of STD
None
6 months
4 months if using NAT,
otherwise 6 months
4 months for new partner, 12
months for multiple partners
6 months
4 months
4 months if using NAT, otherwise 6
months
6 months
12 months
6 months
None
Deferral after Tattoo in Sterile
Environment
6 months
4 months
4 months
6 months
4 months, between 4 months
and 12 months extra test will be
done
None
4 months
6 months
4 months
6 months
None if new needle and new ink
were used
6 months
4 months
6 months
12 months
Deferral after Tattoo in Unsterile or
Unsure of Status Environment
6 months
4 months
4 months
6 months
4 months, between 4 months and 12
months extra test will be done
none if in state that license
tattoo facilities
12 months if in state that does not
license tattoo facilities (DC, GA, ID,
MD, MA, NV, NH, NY, PA, UT, WY)
Deferral after Piercing in Unsterile
or Unsure of Status Environment
6 months
Deferral after Piercing in
Sterile Environment
Platelets- None
Whole Blood, ear piercing- 24
hours
Whole Blood, other piercings- 4
months
None
4 months
6 months
4 months, between 4 months
and 12 months extra test will be
done
none
4 months
4 months
6 months
4 months
6 months
4 months if using NAT, otherwise 6
months
6 months
4 months
6 months
4 months
4 months
6 months
4 months, between 4 months and 12
months extra test will be done
4 months
146 Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
Exposures
Australia
Austria
Belgium
Canada
England and
North Wales
France
Germany
Israel
4 months
6 months
4 months
1 month- non-mucous
membrane (ears, eyebrows,
belly button, etc.)
Lifetime- mucous membrane
piercing (nose, lip, tongue, etc.)
None
6 months
4 months
none
none
Deferral Since
Last Time Donor
Used Illegal IV
Drugs
Lifetime
Lifetime
Lifetime
IV narcotic use
since 1977-Lifetime
Illegal steroids- 12
months
Lifetime
Lifetime
Lifetime
Lifetime
Italy
Japan
Lifetime
6 months
Spain
Lifetime
Sweden
Switzerland
The
Netherlands
Lifetime
Lifetime
Lifetime
United States
Exposures
Australia
Austria
Belgium
Canada
4 months
6 months
4 months
1 month- non-mucous membrane
(ears, eyebrows, belly button, etc.)
Lifetime- mucous membrane piercing
(nose, lip, tongue, etc.)
4 months if using NAT, otherwise 6
months
6 months
4 months
6 months
12 months
Deferral Since Last
Sexual Activity with
Illegal IV Drug User
Deferral Since Last
Time Donor Used NonIV Illegal Drugs
12 months
4 months
12 months
12 months
None
Lifetime- snorting drugs
4 months
12 months- intranasal
cocaine use
12 months
None
4 months
6 months
4 months if using NAT,
otherwise 6 months
12 months
12 months
12 months
None
Cannot be addicted
Deferral for all drug use
other than smoking
None
6 months- use of
psychoactive drugs
None
None
Lifetime- addicted to
marijuana or cocaine
12 months- snorting
cocaine
Lifetime
12 months
None
Deferral After Time Spent in
Minimum Amount of Time of Stay
Jail or Lockup
for Policy to Apply
12 months
72 hours
None
N/A
12 months
48 hours
147 England and
North Wales
France
Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
Exposure
None
N/A
None
4 months
None
N/A
72 hours
N/A
None
None
N/A
N/A
None
None
N/A
N/A
12 months
Deferral After Travel to Africa
(excluding malaria deferrals)
Australia
Austria
Ebola endemic area- 8 weeks
Lifetime- 6 months or more in
area where AIDS/HIV > 1% of
the population
6 months or more- 5 years
Lifetime - born in Cameroon,
Central African Republic, Chad,
Congo, Equatorial Guinea,
Gabon, Niger, and Nigeria since
1977
72 hours
Deferral After Engaging in Sexual
Activities with an Individual who
was Born or Lived in Africa
12 months
Belgium
Canada
England and
North Wales
France
Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
12 months
Lifetime- individual is from
Cameroon, Central African Republic,
Chad, Congo, Equatorial Guinea,
Gabon, Niger, or Nigeria
12 months
6 months or more- 4 months
Travel- 12 months
Lifetime- Born or lived in central
Africa since 1977
4 months
Lifetime- lived in Chagas
disease endemic area
Lifetime- received blood
transfusion during stay
5 years
Partner has lived in Africa for 6 or
more months in the past 5 years-12
months
12 months
Lifetime- from Cameroon,
Central African Republic, Chad,
Congo, Equatorial Guinea,
Gabon, Niger or Nigeria after
1977, unless using specific FDA
Lifetime- partner from Cameroon,
Central African Republic, Chad,
Congo, Equatorial Guinea, Gabon,
Niger or Nigeria after 1977, unless
using specific FDA approved test
148 Exposures
Australia
Austria
Belgium
Canada
England and
North Wales
France
Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
Exposures
Australia
Austria
approved test
Deferral After
Recovery from
Hepatitis Infection
Hep A and B 12
months, Hep C
lifetime
Hep B and C lifetime
Hep B full recovery,
Hep C lifetime
Hep A 6 months with
clear blood tests,
Hep B and C lifetime
Hep A 12 months,
Hep B and C lifetime
Hep B and C lifetime
ban
Hep A 4 months, Hep
B and C lifetime
5 years
Hep B and C lifetime
Hep A and E 6
months, Hep B and C
lifetime
Hep A 6 months, Hep
B and C lifetime if
contracted after 12th
birthday
Hep A and E 6
months, Hep B once
blood tests are clear,
Hep C lifetime
Hep B and C lifetime
Hep A 3 months, Hep
B and C Lifetime
Lifetime if diagnosed
with viral Hep since
11th birthday,
including EBV and
CMV
Deferral After
Engaging in Sexual
Activities with a
Hemophiliac
12 months
4 months
Deferral After
Exposure from Living
with an Individual
with Hepatitis
12 months
Deferral After
Engaging in Sexual
Activities with
Hepatitis Partner
12 months
4 months
12 months
4 months
12 months
12 months
12 months
12 months
12 months
4 months
4 months
4 months
6 months
6 months
Lifetime
Hep A 1 month
4 months if using NAT,
otherwise 6 months
4 months if using NAT,
otherwise 6 months
12 months
12 months
12 months
12 months
12 months
12 months
Deferral After
Engaging in Sex with
an Individual who
has Used Clotting
Factor Concentrates
12 months
4 months
Deferral After
Receiving Clotting
Factor Concentrates
Lifetime
6 months after receiving
any blood or blood
product
149 Belgium
Canada
England and
North Wales
France
Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
Antibiotic
Use Deferral
Australia
Austria
Belgium
Canada
England and
North Wales
France
Germany
Israel
Italy
Japan
Spain
Sweden
Switzerland
The
Netherlands
United States
12 months
6 months
site specific- either 4
months, 4 months
and test until 12
months, or 12
months
None
12 months
6 months
site specific- either 4
months, 4 months and
test until 12 months, or
12 months
Lifetime
Lifetime
Lifetime
None
Lifetime
Lifetime
6 months after receiving
any blood or blood
product
None
12 months
12 months
12 months
4 months
Lifetime
12 months
12 months
Lifetime
Lifetime
12 months
Completion of
Antibiotics
5 days, not
applicable to acne
treatments
28 days, applicable
to acne treatments
12 months
Recovery from
Infection
No wait
Lifetime
Allowed Temperature
Range
28 days
Men >/= 37.5 C
Females >/= 38 C
<38 C
35.5C-37.5C
<37.8 C
15 days
1 day
7 days
14 days
14 days
28 days
3 days
14 days
3 days
No wait, infection
resolved for 14 days
14 days
14 days
14 days
14 days
7 days
3 days
14 days
14 days
<38 C
“no fever”
<37.4 C
<38 C
<37 C
<38 C
28 days
14 days
<38 C
No wait, may donate
day of last pill
10 days- antibiotic
injection
No wait after
infection resolves
<99.5 F (37.5)
Sources: Australian Blood Services, Osterreichisches Rotes Kreuz, Rode Kruis, Canadian Blood Services, Etablissement
Francais du Sang, DRK Blutspendedienst Niedersachsen, Sachsen-Anhalt, Thuringen, Oldenburg und Bremen, Associazione
Volontari Italiani Sangue (AVIS), Magen David Ado, 日本赤十字社 / Nihonsekijūjisha, Banc de Dang I Texitits, GeBlod,
Blutspende Srk Schweiz, Sanquimn Bloedvoorziening, National Health Services Blood and Transplants, American Red
Cross, United States Food and Drug Administration, AABB
150 Count (Countries with Regulation) VI) Additional Figures and Graphs
10 Maximum Number of Donations , by Gender Females 8 Males 6 4 2 0 Unknown 2 Times 3 Times 4 Times 5 Times 6 Times Sources: Australian Blood Services, Osterreichisches Rotes Kreuz, Rode Kruis, Canadian Blood Services, Etablissement Francais du Sang, DRK Blutspendedienst Niedersachsen, Sachsen-­‐Anhalt, Thuringen, Oldenburg und Bremen, Associazione Volontari Italiani Sangue (AVIS), Magen David Ado, 日本赤十字社 / Nihonsekijūjisha, Banc de Dang I Texitits, GeBlod, Blutspende Srk Schweiz, Sanquimn Bloedvoorziening, National Health Services Blood and Transplants, American Red Cross, United States Food and Drug Administration, AABB Maximum Frequency of Donation for Females 18 and over Australia Austria Canada England and North Wales France Germany Israel Italy Japan-­‐ 200 mL Japan-­‐ 400 mL Spain Sweden 0 20 40 60 Days 80 100 120 Sources: Australian Blood Services, Osterreichisches Rotes Kreuz, Rode Kruis, Canadian Blood Services, Etablissement Francais du Sang, DRK Blutspendedienst Niedersachsen, Sachsen-­‐Anhalt, Thuringen, Oldenburg und Bremen, Associazione Volontari Italiani Sangue (AVIS), Magen David Ado, 日本赤十字社 / Nihonsekijūjisha, Banc de Dang I Texitits, GeBlod, Blutspende Srk Schweiz, Sanquimn Bloedvoorziening, National Health Services Blood and Transplants, American Red Cross, United States Food and Drug Administration, AABB Maximum Frequency of Donation for Males 18 and over Switzerland The Netherlands United States Belgium Australia Austria Canada England and North Wales France Germany Israel Italy Japan-­‐ 200 mL Japan-­‐ 400 mL Spain Sweden 0 20 40 60 Days 80 100 120 Sources: Australian Blood Services, Osterreichisches Rotes Kreuz, Rode Kruis, Canadian Blood Services, Etablissement Francais du Sang, DRK Blutspendedienst Niedersachsen, Sachsen-­‐Anhalt, Thuringen, Oldenburg und Bremen, Associazione Volontari Italiani Sangue (AVIS), Magen David Ado, 日本赤十字社 / Nihonsekijūjisha, Banc de Dang I Texitits, GeBlod, Blutspende Srk Schweiz, Sanquimn Bloedvoorziening, National Health Services Blood and Transplants, American Red Cross, United States Food and Drug Administration, AABB Switzerland The Netherlands United States Belgium 151 VII) Calculations
Protected HIV True Risk by Gender and Sexual Activity
Anal Sex
• Recipient= 0.014 * 0.15= 0.0021
o Prevalence in general population= 0.16%= 0.0016 * 0.0021 = 3.36 x 10-6
infection risk for recipient of insertive anal sex with a random person
individual while using a condom
o On average, 3.2% of men and 12.4% of women are the receivers of
penetrative anal sex in the course of a year.
• Penetrator- Circumcised= 0.0011 * 0.15 * 0.0016= 2.6 x 10-7
• Penetrator- Uncircumcised= 0.0062 * 0.15 * 0.0016= 1.49 x 10-6
o On average, 12.6% of men ages 16 and over engaged in penetrative anal
sex
Vaginal
• Male= 0.0004 * 0.15 * 0.0016= 9.6 x 10-8 = chance of a man becoming infected
with HIV after having protected sex with a random women
• Female= 0.0008 * 0.15 * 0.0016= 1.92 x 10-7 = chance of a women becoming
infected with HIV after having protected sex with a random man
vCJD Risk of Lifting the Travel Ban for UK
(2.49/ 1000) [rate of individuals who are deferred] X (1/2000) [the likelihood an individual
from Britain is a carrier for vCJD]= 1.2: 1,000,000 [total risk for vCJD entering the blood
supply]
9,200,000 [total number of blood donors per year] X (2.49/ 1000) [amount of donors per
1000 presenting donors who are deferred due to vCJD related regulations]= 22,908
additional blood donors X (1/2000)= 11.5 potential vCJD carriers X 1.7 [average number
of donations for a donor per year]= 19.5 possible vCJD infected donations per year
entering the blood supply X 3 [maximum number of blood products each donation can
produce]= 58.65 maximum number of infected blood products
22,908 X 1.7 X 3= 116,830 additional blood products if the vCJD travel ban was lifted
Malaria
"The study predicts that in 5 years, ARC lost over 130,000 donors due to the low return
rates after deferrals for malaria exposure.52 A loss of 130,000 donors over 5 years is
associated with a loss of over 221,000 donations, and up to 663,000 blood products, the
following year.”
“The majority were exposed in “low risk” areas like Mexico (41%), the Caribbean (13%),
and Central America (22%).90 The remaining donors were deferred due to travel to “high
risk” areas like Africa and Oceania.”90
221,000/5= 26,000 * 73%= 18,980/4= 4,745 increased number of donations annually if
Malaria deferral rate was reduced to 3 months for travel to Mexico, increase due to a
smaller percentage of donors deferred who never return even when eligible
152 “The study also found if deferral lengths due to travel to ME areas were reduced from 12
months to 3 months, an additional 56,000 donations would be added to the blood supply
annually, with only one additional malaria contaminated unit collected every 57 years.”91
4,745+56,000= 60,745
à 60,745 additional donations annually with a risk rate of 0.06 malaria infections per
1,000,000 donations
à Increase the number of males disproportionately compared to females
60,745 * 57= 3.5 million donations per additional malaria infection
153 VIII) Prevalence of Deferral Characteristics in America’s Adult Population
Reason for Deferral
Prevalence in the
General Population
(18- 69)
5.36%
5.09%
1.72%
3.15%
1.74%
2.61%
1.17%
Cancer
Low Hb
Underweight
HBV Infection
HCV Infection
Pregnancy
Body Piercing
Institutionalization
IV Drug Use
MSM
Accidental Needle Stick
Tattoo
Travel to Africa
Immigrant from Malaria
Region
Travel to Malaria Region
UK Travel
HIV Positive
Heart Attack
Coronary Heart Disease
Total Deferral Factors
1.18%
0.17%
1.38%
0.43%
3.00%
0.04%
0.75%
Most Prevalent Demographic
(AA, White, Hispanic, Male,
Female, <40, and <40)
40-69 years old (8.23%)
African Americans (11.97%)
Females (3.32%)
African Americans (8.93%)
African Americans (3.00%)
Hispanics (5.63%)
White (1.17%), Female (1.17%),
18-39 (1.17%)
African American (3.92%)
Hispanic (0.27%)
Hispanic (2.15%)
Hispanic (0.59%)
Hispanic (6.80%)
Statistically insignificant
Males (0.91%)
0.60%
0.02%
0.16%
1.87%
1.95%
42.63%
Males (0.64%)
Statistically insignificant
African Americans (0.71%)
40-69 years old (3.08%)
40-69 years old (3.41%)
African Americans (58.78%)
SOURCE: James, A. et. al. Transfusion, 2012 (52):1050-1061
154 IIX) Glossary of Acronyms
AIS-­‐ Absent Iron Stores ARC-­‐ American Red Cross CBER-­‐ Center for Biologics Evaluation and Response CDC-­‐ Center for Disease Control and Prevention CFR-­‐ Code of Federal Regulations CI-­‐ Confidence Interval CJD-­‐ Creutzfeldt-­‐Jakob's Disease vCJD-­‐ Variant Creutzfeldt-­‐Jakob's Disease CSF-­‐ Consecutive Symptom-­‐Free EBV-­‐ Estimated Blood Volume FDA-­‐ Food and Drug Administration FTD-­‐ first time donors HV-­‐ Hepatitis Virus HAV-­‐ Hepatitis A Virus HBV-­‐ Hepatitis B Virus HCV-­‐ Hepatitis C Virus Hb-­‐ Hemoglobin HIV-­‐ Human Immunodeficiency Virus IAD-­‐ Iron Depletion Anemia ID-­‐ Iron Depletion IDU-­‐ IV Drug User ME-­‐ Malaria-­‐Endemic MSM-­‐ Men who have Sex with Other Men NAT-­‐ Nucleic Acid Testing ID-­‐NAT-­‐ Individual Nucleic Acid Testing MP-­‐NAP-­‐ Mini-­‐Pooling Nucleic Acid Testing NME-­‐ Non-­‐Malaria Endemic OR-­‐ Odds Ratio RBC-­‐ Red Blood Cells RD-­‐ repeat donors STI-­‐ Sexually Transmitted Infections TTI-­‐ transfusion transmitted infection WNV-­‐ West Nile Virus WSW-­‐ Women who have Sex with Other Women 155 IX) Donor History Questionnaire 156 157 X) Center for Disease Control and Prevention Malaria Exposure Traveler Map 88
Sources
1.
Pfuntner A, Wier L, Stocks C. STATISTICAL BRIEF - Most Frequent Procedures
Performed in U.S. Hospitals, 2010. Agency for Healthcare Research and Quality.
http://www.hcup-us.ahrq.gov/reports/statbriefs/sb149.pdf. Published 2013.
2.
What is Blood? Am Blood Centers. 2012:1. http://www.americasblood.org/aboutblood/what-is-blood.aspx. Accessed June 12, 2014.
3.
Blood Components. Am Red Cross. 2012:1. http://www.redcrossblood.org/learnabout-blood/blood-components#blood_components_table. Accessed July 12,
2014.
4.
Blood. Natl Institutes Heal Medlin. 2014.
http://www.nlm.nih.gov/medlineplus/blood.html. Accessed July 12, 2014.
5.
Blood Facts and Statistics. Am Red Cross. 2014.
http://www.redcrossblood.org/learn-about-blood/blood-facts-and-statistics#bloodsupply. Accessed June 12, 2014.
6.
Almizraq R, Tchir JDR, Holovati JL, Jason P. Storage of red blood cells affects
membrane composition, microvesiculation, and in vitro quality. Transfusion.
2013;53(October):2258-2267. doi:10.1111/trf.12080.
7.
Wagner T, Pabst MA, Leitinger G, et al. Impact of constant storage temperatures
and multiple warming cycles on the quality of stored red blood cells. Vox Sang.
2014;106:45-54. doi:10.1111/vox.12074.
8.
Platelets. Am Red Cross. 2014. http://www.redcrossblood.org/learn-aboutblood/blood-components/platelets. Accessed June 12, 2014.
9.
George JN. Platelets. Lancet. 2000;355(April):1531-1539. doi:10.1016/S01406736(00)02175-9.
10.
Stroncek DF, Rebulla P. Platelet transfusions. Lancet. 2007;370(August):427-438.
http://ac.els-cdn.com.resources.library.brandeis.edu/S0140673607611982/1-s2.0S0140673607611982-main.pdf?_tid=808ddcae-937e-11e4-b91000000aacb360&acdnat=1420313406_0c0d232d59fc9e690a67f94f9537bb5b.
11.
Medical Descriptor Data: Leukocytes. Natl Libr Med. 2001.
http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?mode=&index=7602&view=conce
pt. Accessed August 12, 2014.
12.
Leukocytes. Natl Cent Biotechnol Inf.
http://www.ncbi.nlm.nih.gov/mesh/68007962. Accessed August 12, 2014.
13.
Plasma. Am Red Cross. 2014. http://www.redcrossblood.org/learn-aboutblood/blood-components/plasma. Accessed June 12, 2014.
159 14.
Blood Component Therapy: Cryoprecipitate (CRYO). Puget Sound Blood Cent.
2014. http://www.psbc.org/therapy/cryo.htm. Accessed July 12, 2014.
15.
Gilliss BM, Looney MR, Gropper MA. Reducing noninfectious risks of blood
transfusion. Anesthesiology. 2011;115:635-649.
doi:10.1097/ALN.0b013e31822a22d9.
16.
Blood Testing. Am Red Cross. http://www.redcrossblood.org/learn-aboutblood/what-happens-donated-blood/bloodtesting#Chagas__disease__T._cruzi___2007_. Accessed August 2, 2015.
17.
Hepatitis C Information for Health Professionals. Centers Dis Control Prev Div
HIV/AIDS Prev Natl Cent HIV/AIDS, Viral Hepatitis, Sex Transm Dis Tuberc Prev.
2015. http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm.
18.
James AB, Hillyer CD, Shaz BH. Demographic differences in estimated blood
donor eligibility prevalence in the United States. Transfusion. 2012;52(May):10501061. doi:10.1111/j.1537-2995.2011.03416.x.
19.
Zabarenko D. The Nation Has a Major Blood Shortage. ABC News.
http://abcnews.go.com/Health/story?id=117954. Published 2014.
20.
Vogel TR, Dombrovskiy VY, Lowry SF. In-hospital delay of elective surgery for
high volume procedures: The impact on infectious complications. J Am Coll Surg.
2010;211(6):784-790. doi:10.1016/j.jamcollsurg.2010.08.009.
21.
Sobolev BG, Levy AR, Kuramoto L, Hayden R, Brophy JM, FitzGerald JM. The
risk of death associated with delayed coronary artery bypass surgery. BMC Health
Serv Res. 2006;6:85. doi:10.1186/1472-6963-6-85.
22.
About FDA: CBER Vision & Mission. US Food Drug Adm. 2014:1-2.
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacc
o/CBER/ucm122878.htm.
23.
Blood & Blood Products. US Food Drug Adm. 2014:1-3.
http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/default.htm.
24.
Advisory Committees Charter of the Blood Products Advisory Committee. US
Food Drug Adm. 2014;(c):1-3.
http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVacci
nesandOtherBiologics/BloodProductsAdvisoryCommittee/ucm121602.htm.
25.
Code of Federal Regulations Title 21. 2014.
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm.
26.
Guidance for Industry: Recommendations for Deferral of Donors and Quaratine
and Retrieval of Blood and Blood Products in Recent Recipients of Smallpox
Vaccine (Vaccinia Virus) and Certain Contacts of Smallpox Vaccine Recipients.
Rockville, MD; 2002:1-9.
160 27.
Guidance for Industry Revised Preventive Measures to Reduce the Possible Risk
of Transmission of Creutzfedt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob
Disease (vCJD) by Blood and Blood Products. Rockville, MD; 2010:1-51.
28.
Sher G, Markowitz MA. AABB 2013 Annual Report.; 2014:1-14.
http://www.aabb.org/about/who/Documents/2013-annual-report.pdf.
29.
About AABB. AABB. 2014:2-4. http://www.aabb.org/about/Pages/default.aspx.
Accessed February 1, 2015.
30.
Organization Overview. AABB. 2014:1-8.
http://www.aabb.org/about/who/Pages/overview.aspx. Accessed December 1,
2015.
31.
National Blood Exchange. AABB. 2015:1-4.
http://www.aabb.org/programs/nbe/Pages/default.aspx. Accessed February 1,
2015.
32.
McElveen-Hunter B, McGovern G. 2013 Annual Report.; 2013:1-25.
http://www.redcross.org/images/MEDIA_CustomProductCatalog/m39440096_201
3AnnualReport.pdf.
33.
Flores AB, Connor DJ. Blood Systems 2013 Annual Report.; 2013:1-11.
http://www.flipsnack.com/FFAA75AD75E/funs7sq0.html.
34.
Custer B, Chinn A, Hirschler N V., Busch MP, Murphy EL. The consequences of
temporary deferral on future whole blood donation. Transfusion. 2007;47:15141523. doi:10.1111/j.1537-2995.2007.01292.x.
35.
Custer BS, Schlumpf K, Simon TL, Spencer BR, Wright DJ, Wilkinson SL.
Demographics of successful, unsuccessful and deferral visits at six blood centers
over a 4-year period. Transfusion. 2012;52(April):712-721. doi:10.1111/j.15372995.2011.03353.x.
36.
Ditto B, Gilchrist PT, Holly CD. Fear-related predictors of vasovagal symptoms
during blood donation: it’s in the blood. J Behav Med. 2012;35(4):393-399.
doi:10.1007/s10865-011-9366-0.
37.
Vasovagal Syncope. Mayo Found Med Educ Res. 2013.
http://www.mayoclinic.org/diseases-conditions/vasovagalsyncope/basics/definition/con-20026900.
38.
Ditto B, Balegh S, Gilchrist PT, Holly CD. Relation between perceived blood loss
and vasovagal symptoms in blood donors. Clin Auton Res. 2012;22(2):113-116.
doi:10.1007/s10286-011-0147-1.
39.
France CR, France JL, Kowalsky JM, et al. Assessment of donor fear enhances
prediction of presyncopal symptoms among volunteer blood donors. Transfusion.
2012;52(February):375-380. doi:10.1111/j.1537-2995.2011.03294.x.
161 40.
Bravo M, Kamel H, Custer BS, Tomasulo P. Factors associated with fainting –
before, during and after whole blood donation. Vox Sang. 2011;101:303-312.
doi:10.1111/j.1423-0410.2011.01494.x.
41.
Notari EP, Zou S, Fang CT, Eder AF, Benjamin RJ, Dodd RY. Age-related donor
return patterns among first-time blood donors in the United States. Transfusion.
2009;49(October):2229-2236. doi:10.1111/j.1537-2995.2009.02288.x.
42.
Lam J, Bruhn R, Custer BS, Murphy EL. Water administration and the risk of
syncope and presyncope during blood donation: a randomized clinical trial.
Transfusion. 2012;52(December):2577-2584. doi:10.1111/j.15372995.2012.03631.x.
43.
Fatalities Reported to FDA Following Blood Collection and Transfusion. Rockville,
MD; 2013:2.
http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/Tra
nsfusionDonationFatalities/ucm391574.htm.
44.
Goldman M, Osmond L, Yi Q, Cameron-Choi K, O’Brien SF. Frequency and risk
factors for donor reactions in an anonymous blood donor survey. Transfusion.
2013;53(September):1979-1984. doi:10.1111/trf.12011.
45.
Newman B. Syncope after whole blood donation: factors associated with
increased donor reaction. Transfusion. 2012;52(January):210-212.
46.
Vamvakas EC, Blajchman MA. Transfusion-related mortality  : the ongoing risks of
allogeneic blood transfusion and the available strategies for their prevention.
2011;113(15):3406-3417. doi:10.1182/blood-2008-10-167643.
47.
Zia M, Besa EC. Transfusion- Transmitted Diseases. Medscape. 2014:1-11.
48.
Sarode R. Complications of Transfusion. Merck. 2014:1-12.
http://www.merckmanuals.com/professional/hematology_and_oncology/transfusio
n_medicine/complications_of_transfusion.html. Accessed December 12, 2014.
49.
Human Development Report 2013.; 2013:1-216. doi:ISBN: 978-92-1-126340-4.
50.
World Development Indicators. World Bank. 2012.
http://databank.worldbank.org/data/home.aspx.
51.
The World Factbook 2013-14. Washington, D.C.; 2013.
https://www.cia.gov/library/publications/the-world-factbook/fields/2177.html.
52.
Zou S, Musavi F, Notari EP, Rios J a., Trouern-Trend J, Fang CT. Donor deferral
and resulting donor loss at the American Red Cross Blood Services, 2001 through
2006. Transfusion. 2008;48(December):2531-2539. doi:10.1111/j.15372995.2008.01903.x.
162 53.
Eligibility Criteria by Topic. Am Red Cross. 2014:1-6.
http://www.redcrossblood.org/donating-blood/eligibility-requirements/eligibilitycriteria-topic. Accessed November 11, 2014.
54.
Graham DT. Prediction of Fainting in Blood Donors. Circulation.
1961;XXIII(June):901-906.
55.
Kessler DA, ed. Statement on Blood Pressure and Pulse as Blood Donor
Eligilbility Criteria. In: Blood Products Advisory Committee. AABB; 2009:1-3.
56.
Wiltbank TB, Giordano GF, Kamel H, Tomasulo P, Custer BS. Faint and prefaint
reactions in whole-blood donors: an analysis of predonation measurements and
their predictive value. Transfusion. 2008;48(September):1799-1808.
doi:10.1111/j.1537-2995.2008.01745.x.
57.
Thomas D, Bolton-Maggs P. Annual SHOT Report 2013. United Kingdom; 2013.
http://www.shotuk.org/wp-content/uploads/74280-SHOT-2014-Annual-ReportV12-WEB.pdf.
58.
Interview with Mindy Goldman of the Canadian Blood Services. 2014.
59.
Blood Pressure. Am Hear Assoc. 2014. http://www.heart.org/HEARTORG/.
60.
Tests and Procedures: Hemoglobin test. Mayo Found Med Educ Res. 2015.
http://www.mayoclinic.org/tests-procedures/hemoglobin-test/basics/definition/prc20015022. Accessed August 3, 2015.
61.
Zheng H, Cable R, Spencer B, Votto N, Katz SD. Iron stores and vascular function
in voluntary blood donors. Arterioscler Thromb Vasc Biol. 2005;25:1577-1583.
doi:10.1161/01.ATV.0000174126.28201.61.
62.
Cable RG, Glynn SA, Kiss JE, et al. Iron deficiency in blood donors: The REDS-II
Donor Iron Status Evaluation (RISE) study. Transfusion. 2012;52:702-711.
doi:10.1111/j.1537-2995.2011.03401.x.
63.
Waldvogel S, Pedrazzini B, Vaucher P, et al. Clinical evaluation of iron treatment
efficiency among non-anemic but iron-deficient female blood donors: a
randomized controlled trial. BMC Med. 2012;10:8. doi:10.1186/1741-7015-10-8.
64.
Eder AF, Hillyer CD, Dy B a, Notari EP, Benjamin RJ. Adverse reactions to
allogeneic whole blood donation by 16- and 17-year-olds. JAMA.
2008;299(19):2279-2286.
65.
Age Distribution of Blood Donors, by Country. Geneva; 2010:1.
http://www.who.int/worldblooddonorday/media/Donor_age_distribution_2008.pdf.
66.
Shehata N, Kusano R, Hannach B, Hume H. Reaction rates in allogeneic donors.
Transfus Med. 2004;14:327-333.
163 67.
Goldman M, Fournier E, Cameron-Choi K, Steed T. Effect of changing the age
criteria for blood donors. Vox Sang. 2007;92:368-372. doi:10.1111/j.14230410.2007.00897.x.
68.
Zeiler T, Lander-Kox J, Alt T. Blood donation by elderly repeat blood donors.
Transfus Med hemotherapy. 2014;41:242-250. doi:10.1159/000365401.
69.
Comeau PJ. The blood loss analyzer--a new way to estimate blood loss. J Am
Assoc Nurse Anesth. 1983;51:81-84.
70.
Rios JA, Fang J, Tu Y, et al. The potential impact of selective donor deferrals
based on estimated blood volume on vasovagal reactions and donor deferral
rates. Transfusion. 2010;50:1265-1275. doi:10.1111/j.1537-2995.2009.02578.x.
71.
Walpole SC, Prieto-Merino D, Edwards P, Cleland J, Stevens G, Roberts I. The
weight of nations: an estimation of adult human biomass. BMC Public Health.
2012;12:439. doi:10.1186/1471-2458-12-439.
72.
Birgegård G, Schneider K, Ulfberg J. High incidence of iron depletion and restless
leg syndrome (RLS) in regular blood donors: Intravenous iron sucrose substitution
more effective than oral iron. Vox Sang. 2010;99:354-361. doi:10.1111/j.14230410.2010.01368.x.
73.
Kruskall MS, Leonard S, Klapholz H. Autologous blood donation during
pregnancy: analysis of safety and blood use. Obstet Gynecol. 1987;70:938-941.
74.
Edgren G, Hjalgrim H, Reilly M, et al. Risk of cancer after blood transfusion from
donors with subclinical cancer: a retrospective cohort study. Lancet.
2007;369:1724-1730. doi:10.1016/S0140-6736(07)60779-X.
75.
Can I donate blood if I have had cancer? Cancer Res UK. 2013.
http://www.cancerresearchuk.org/about-cancer/cancers-in-general/cancerquestions/can-i-donate-blood-if-i-have-had-cancer.
76.
Cancer- I had cancer. Can I donate? Aust Red Cross Blood Serv. 2014.
77.
Sojka BN, Sojka P. Blood donation constitutes only a barely discernible triggering
factor of myocardial infarction. Int Jounal Cardiol. 2007;120(1):127-128.
78.
Germain M, Delage G, Blais C, Maunsell E, Décary F, Grégoire Y. Iron and
cardiac ischemia: a natural, quasi-ransom experiment comparing eligible with
disqualified blood donors. Transfusion. 2013;53(June):1271-1279.
doi:10.1111/trf.12081.
79.
Kasper SM, Ellering J, Stachwitz P, Lynch J, Grunenberg R, Buzello W. All
Adverse Events in Autologous Blood Donors with Cardiac Disease Are Not
Necessarily Caused by Blood Donation. Transfusion 38, 669-673 (1998).
doi:10.1046/j.1537-2995.1998.38798346636.x.
164 80.
Fast Facts Data and Statistics about Diabetes. 2015:2.
http://professional.diabetes.org/ResourcesForProfessionals.aspx?cid=91777&loc=
dorg-statistics.
81.
Fernández-Real JM, López-Bermejo A, Ricart W. Iron stores, blood donation, and
insulin sensitivity and secretion. Clin Chem. 2005;51:1201-1205.
doi:10.1373/clinchem.2004.046847.
82.
Stainsby D, Brunskill S, Chapman CE, Dorée C, Stanworth S. Safety of blood
donation from individuals with treated hypertension or non-insulin dependent type
2 diabetes - A systematic review. Vox Sang. 2010;98:431-440.
doi:10.1111/j.1423-0410.2009.01275.x.
83.
Jiang R, Ma J, Ascherio A, Stampfer MJ, Willett WC, Hu FB. Dietary iron intake
and blood donations in relation to risk of type 2 diabetes in men: a prospective
cohort study. Am J Clin Nutr. 2004;79:70-75.
http://www.ncbi.nlm.nih.gov/pubmed/14684399.
84.
Kitchen AD, Chiodini PL. Malaria and blood transfusion. Vox Sang. 2006;90:7784. doi:10.1111/j.1423-0410.2006.00733.x.
85.
Malaria Facts. Centers Dis Control Prev Glob Heal Div Parasit Dis Malar. 2014.
86.
Disease: Malaria. Centers Dis Control Prev. 2010:1-4.
http://www.cdc.gov/malaria/about/disease.html.
87.
Malaria centre. World Heal Organ. 2014:1-8.
http://www.who.int/mediacentre/factsheets/fs094/en/.
88.
Malaria Information and Prophylaxis. Centers Dis Control Prev. 2014:2-3.
http://www.cdc.gov/malaria/travelers/country_table/a.html.
89.
Guidance for Industry Guidance for Industry Recommendations for Donor
Questioning, Deferral, Reentry and Product Management to Reduce the Risk of
Transfusion-Transmitted Malaria. Rockville, MD; 2014:1-15.
90.
Spencer B, Steele W, Custer B, et al. Risk for malaria in United States donors
deferred for travel to malaria-endemic areas. Transfusion. 2009;49:2335-2345.
doi:10.1111/j.1537-2995.2009.02290.x.
91.
Spencer B, Steele W, Custer B, et al. Risk for malaria in United States donors
deferred for travel to malaria-endemic areas. Transfusion. 2009;49:2335-2345.
doi:10.1111/j.1537-2995.2009.02290.x.
92.
Chagas disease (American trypanosomiasis). World Heal Organ. 2014.
http://www.who.int/mediacentre/factsheets/fs340/en/.
165 93.
Parasites- American Trypanosomiasis (also known as Chagas Disease). Centers
Dis Control Prev Glob Heal Div Parasit Dis Malar. 2013.
http://www.cdc.gov/parasites/chagas/.
94.
Parasites- Babesiosis. Centers Dis Control Prev Glob Heal Div Parasit Dis Malar.
2014. http://www.cdc.gov/parasites/babesiosis/.
95.
Ticks-Geographic Distribution. Centers Dis Control Prev Natl Cent Emerg
Zoonotic Infect Dis. 2014.
96.
Weissman R. Interview with Anne Eder, Cheif Medical Officer of the American
Red Cross.
97.
What Happens to Blood Donors Who Test Positive for Chagas’ Disease? :1.
http://www.cdc.gov/parasites/chagas/resources/A_Test
Positive_Chagas_Flyer_508.pdf.
98.
Immunetics Receives $3.7 Million NIH Contract for Babesia Blood Screening Test.
Immunetics. 2012. http://www.immunetics.com/pr_120910.html. Accessed
September 4, 2015.
99.
Levin AE, Williamson PC, Erwin JL, et al. Determination of Babesia microti
seroprevalence in blood donor populations using an investigational enzyme
immunoassay. Transfusion. 2014;54:2237-2244.
100. Guidance for Industry: Assessing Donor Suitability and Blood and Blood Product
Safety in Cases of Known or Suspected West Nile Virus Infection. Rockville, MD;
2005:1-13.
101. Guidance For Industry: Use of Nucleic Acid Tests to Reduce the Risk of
Transmission of West Nile Virus from Donors of Whole Blood and Blood
Components Intended for Transfusion. Rockville, MD; 2009:1-10.
102. Kelly S, Le TN, Brown JA, et al. Fatal West Nile Virus Infection After Probable
Transfusion-Associated Transmission — Colorado, 2012. Morb Mortal Wkly Rep.
2013;62(31):622-624.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6231a2.htm.
103. CJD (Creutzfeldt-Jakob Disease, Classic). Centers Dis Control Prev. 2014.
http://www.cdc.gov/ncidod/dvrd/cjd/. Accessed November 12, 2014.
104. vCJD (Variant Creutzfeldt-Jakob Disease). Centers Dis Control Prev. 2014.
http://www.cdc.gov/ncidod/dvrd/vcjd/factsheet_nvcjd.htm. Accessed November
12, 2014.
105. BSE (Bovine Spongiform Encephalopathy, or Mad Cow Disease). Centers Dis
Control Prev Natl Cent Emerg Zoonotic Infect Dis. 2013.
http://www.cdc.gov/ncidod/dvrd/bse/.
166 106. BSE Incidence/ Cases. Natl Cattleman’s Beef Assoc. 2014.
http://www.bseinfo.org/bseincidencecases.aspx.
107. Gill ON, Spencer Y, Richard-Loendt A, et al. Prevalent abnormal prion protein in
human appendixes after bovine spongiform encephalopathy epizootic: large scale
survey. BMJ. 2013;347(October):1-12. doi:10.1136/bmj.f5675.
108. CREUTZFELDT-JAKOB DISEASE IN THE UK. Univ Edinburgh Natl CJDResearch Surveill Unit. 2015:1. http://www.cjd.ed.ac.uk/documents/figs.pdf.
109. Collinge J, Whitfield J, McKintosh E, et al. Kuru in the 21st century-an acquired
human prion disease with very long incubation periods. Lancet. 2006;367:20682074. doi:10.1016/S0140-6736(06)68930-7.
110. Nunez C. Mad Cow Disease Still Menaces U.K. Blood Supply. Natl Geogr Mag.
2015. http://news.nationalgeographic.com/news/2015/02/150215-mad-cowdisease-vcjd-blood-supply-health/.
111. Wroe SJ, Pal S, Siddique D, et al. Clinical presentation and pre-mortem diagnosis
of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case
report. Lancet. 2006;368:2061-2067 ST - Clinical presentation and pre - mortem .
doi:S0140-6736(06)69835-8 [pii] 10.1016/S0140-6736(06)69835-8.
112. Mason R. Mad cow infected blood “to kill 1,000.” The Telegraph. April 28, 2013.
113. Brown P, Brandel JP, Sato T, et al. Iatrogenic creutzfeldt-Jakob disease, final
assessment. Emerg Infect Dis. 2012;18:901-907. doi:10.3201/eid1806.120116.
114. Laffoon B, Crutchfield A, Levi M, et al. HIV Transmission Through TransfusionMissouri and Colorado, 2008. Morb Mortal Wkly Rep. 2010;59(15):1335-1339.
115. HIV in the United States: At A Glance. Centers Dis Control Prev Div HIV/AIDS
Prev Natl Cent HIV/AIDS, Viral Hepatitis, Sex Transm Dis Tuberc Prev. 2014.
http://www.cdc.gov/hiv/statistics/basics/ataglance.html. Accessed November 3,
2015.
116. Chan SK, Thornton LR, Chronister KJ, et al. Likely Female-to-Female Sexual
Transmission of HIV - Texas, 2012. MMWR Morb Mortal Wkly Rep. 2014;63:209212. http://www.ncbi.nlm.nih.gov/pubmed/24622284.
117. HIV Among Gay and Bisexual Men. Centers Dis Control Prev Div HIV/AIDS Prev
Natl Cent HIV/AIDS, Viral Hepatitis, Sex Transm Dis Tuberc Prev. 2015.
http://www.cdc.gov/hiv/risk/gender/msm/facts/index.html. Accessed November 3,
2015.
118. Dayton AI, Anderson SA, Yang H, et al. Quantitative estimate of the risks and
benefits of possible alternative blood donor deferral strategies for men who have
had sex with men. Transfusion. 2009;49:1102-1114. doi:10.1111/j.15372995.2009.02124.x.
167 119. Quigley M, Baldwin T, Enzi M, Warren E, Lee B. Letter to The Honorable Kathleen
Sebelius. 2013.
120. Bierman N. Warren Demands US Ends Ban on Blood Donations from Gay Men.
Boston Globe. 2013.
121. Global Report: UNAIDS Report on the Global AIDS Epidemic 2013. Geneva,
Switerland; 2013.
http://www.unaids.org/sites/default/files/en/media/unaids/contentassets/document
s/epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_en.pdf.
122. Viral Hepatitis. Centers Dis Control Prev Div HIV/AIDS Prev Natl Cent HIV/AIDS,
Viral Hepatitis, Sex Transm Dis Tuberc Prev. 2014. http://www.cdc.gov/hepatitis/.
Accessed November 3, 2015.
123. HIV/AIDS and Viral Hepatitis. Centers Dis Control Prev Div HIV/AIDS Prev Natl
Cent HIV/AIDS, Viral Hepatitis, Sex Transm Dis Tuberc Prev. 2014.
124. United Nations Office on Drugs and Crime. World Drug Report 2013. Joost.
2013;2013:316. doi:10.1002/yd.20002.
125. Infection Control: Frequently Asked Questions- Bloodborne PathogensOccupational Exposure. Centers Dis Control Prev. 2015.
http://www.cdc.gov/oralhealth/infectioncontrol/faq/bloodborne_exposures.htm.
126. Baggaley RF, White RG, Boily M-C. HIV transmission risk through anal
intercourse: systematic review, meta-analysis and implications for HIV prevention.
Int J Epidemiol. 2010;39:1048-1063. doi:10.1093/ije/dyq057.
127. Jin F, Jansson J, Law M, et al. Per-contact probability of HIV transmission in
homosexual men in Sydney in the era of HAART. AIDS. 2010;24:907-913.
doi:10.1097/QAD.0b013e3283372d90.
128. Boily MC, Baggaley RF, Wang L, et al. Heterosexual risk of HIV-1 infection per
sexual act: systematic review and meta-analysis of observational studies. Lancet
Infect Dis. 2009;9:118-129. doi:10.1016/S1473-3099(09)70021-0.
129. Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per
coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis.
2005;191:1403-1409. doi:10.1086/429411.
130. Wilton J. Putting a number on it: The risk from an exposure to HIV. CATIE. 2012.
http://www.catie.ca/en/pif/summer-2012/putting-number-it-risk-exposure-hiv.
131. Hepatitis B FAQs for the Public. Centers Dis Control Prev Div HIV/AIDS Prev Natl
Cent HIV/AIDS, Viral Hepatitis, Sex Transm Dis Tuberc Prev. 2015.
http://www.cdc.gov/hepatitis/B/bFAQ.htm.
132. Zuckerman AJ. Hepatitis Viruses. Med Microbiol. 1996.
168 133. Hepatitis C & Incarceration. Centers Dis Control Prev. 2013.
http://www.cdc.gov/hepatitis/HCV/PDFs/HepCIncarcerationFactSheet.pdf.
134. HIV in Correctional Settings. Centers Dis Control Prev Div HIV/AIDS Prev Natl
Cent HIV/AIDS, Viral Hepatitis, Sex Transm Dis Tuberc Prev. 2014.
http://www.cdc.gov/hiv/risk/other/correctional.html.
135. Spach DH. HCV Epidemiology in the United States. Hepat C Online. 2014.
http://www.hepatitisc.uw.edu/go/screening-diagnosis/epidemiology-us.
136. Meier B. Blood, Money and AIDS: Hemophiliacs Are Split;Liability Cases Bogged
Down in Disputes. The New York Times. June 11, 1996.
137. Hepatitis A Among Persons with Hemophilia Who Received Clotting Factor
Concentrate-- United States, September-December 1996. Morb Mortal Wkly Rep.
1996;45(2):29-32. http://www.cdc.gov/mmwr/preview/mmwrhtml/00039962.htm.
138. Stramer SL. Current risks of transfusion-transmitted agents: A review. Arch Pathol
Lab Med. 2007;131:702-707. doi:10.1043/15432165(2007)131[702:CROTAA]2.0.CO;2.
139. Magill SS, Edwards JR, Beldavs ZG, et al. Prevalence of Antimicrobial Use in US
Acute Care Hospitals, May-September 2011. JAMA. 2014;312(14):1438-1446.
http://jama.jamanetwork.com/article.aspx?articleid=1911328.
140. Cori A, Valleron A, Carrat F, Tomba GS, Thomas G, Boelle P. Estimating
influenza latency and infectious period durations using viral excretion data.
Epidemics. 2012;4(3):132-138.
http://www.sciencedirect.com/science/article/pii/S175543651200031X.
141. Schmitt BD. My Child Is Sick. American Academy of Pediatrics Books; 2014.
http://www.childrenshealthnetwork.org/CRS/CRS/pa_incubate_hhg.htm.
142. Garozzo G, Crocco I, Giussani B, Martinucci A, Monacelli S, Randi V. Adverse
reactions to blood donations: The READ project. Blood Transfus. 2010;8:49-62.
doi:10.2450/2009.0089-09.
143. Brucker G, Therre H, Hoile E. Eurosurveillance: viral safety of blood. Eur Commun
Dis Q. 2005;10(1-3).
http://www.eurosurveillance.org/images/dynamic/eq/v05n01/v05n01.pdf.
144. Transfusion Transmitted Injuries. Public Heal Agency Canada. 2004.
http://www.phac-aspc.gc.ca/hcai-iamss/tti-it/risks-eng.php.
145. Condom Effectiveness. AIDS Found Chicago Campaign Love One You’re With.
146. External (Male) Condoms. Options Sex Heal. 2009.
https://www.optionsforsexualhealth.org/birth-control-pregnancy/birth-controloptions/barrier-methods/condom-male. Accessed September 4, 2015.
169 147. Carey R, Herman W, Retta S, Rinaldi J, Herman B, Athey T. Effectiveness of latex
condoms as a barrier to human immunodeficiency virus-sized particles under
conditions of simulated use. J Sex Transm Dis. 1992;19(4):230-234.
148. Frequently Asked Sexuality Questions to The Kinsey Institute. Kinsey Inst.
http://www.kinseyinstitute.org/resources/FAQ.html#frequency. Accessed August
4, 2015.
149. Harding AJ. A brief history of blood transfusion. Inst Biomed Sci. 2005.
https://www.ibms.org/go/nm:history-blood-transfusion. Accessed September 2,
2015.
150. Highlights of Transfusion Medicine History. AABB.
151. Schwartz RS, Conley CL. Blood. Encycl Br. 2014:Web.
http://www.britannica.com/EBchecked/topic/69685/blood.
170