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Transfusion Medicine
Reference:Harrison’s principle of internal Medicine
16th edition chapter 99 pages 662-667
L. Bonstein PhD
E. J. Dann MD
• In 1901 Karl Landsteiner discovered the ABO
blood groups.
• In 1914 the effect of sodium citrate was
described.
• In 1915 the first successful transfusion of
preserved blood took place.
• In 1920 the first blood banks were created in
Paris and SAN PETERSBURG
• In 1932 the !st blood bank was established in
Chicago
• Combat conditions blood bank was 1st used
during the Spanish civil war
LANCET
April 1 1939
236:773-775
• In 1940 the "Rhesus" system was discovered
by Levine, together with Landsteiner and
Wiener.
• In the Second World War about 50,000
transfusions of preserved blood were given
on the German side and millions on the
Allied side.
• After the Second World War: improvement in
the stabilizing solutions.
• Today: separation of blood into various
blood components.
Close Circuit Donation System
Preservation solutions
ADSOL 100ml
CPDA 60ml
More Adenine
Mannitol
Citrate
Phosphate
Dextrose
Adenine
‫)‪Whole Blood (historical option‬‬
‫•‬
‫•‬
‫•‬
‫•‬
‫•‬
‫•‬
‫מכיל את כל מרכיבי הדם‬
‫יינתן במקרים של איבוד דם רב‬
‫ניתן לפי סוג ולאחר הצלבה‬
‫נשמר במקרר עד ‪ 35‬ימים‬
‫‪35-45% 450ml‬‬
‫הפלזמה במוצר זה בעלת ערך‬
‫אונקוטי בלבד ולא מכילה‬
‫פקטורי קרישה –מד”א הפסיק‬
‫לספק מוצר זה לאחרונה‪.‬‬
‫תהליך הפרשת הפלזמה ממנת הדם ויצירת ‪PACKED CELL‬‬
Packed Red Blood Cells (PC)
One unit of packed RBC will
raise Pt hemoglobin 1
gr/100ml
Unit volume 250-350 ml Hct of
70%-60%
Indication: acute bleeding
Anemia with Hb of less
then7gr% or ischemic Pt with
less then 12 gr%
Storage period 35 or 42 days at
1-60c
Type and cross
Platelets Concentrates
• A unit of platelets contain 5x1010
increase count of platelets by 10000/ul
(20-30ml)
• Adult dose is 6 units
• Platelet count should be kept above 510 x103 /ul or 50 x103 /ul in acute
bleeding
• Platelets concentrate are kept at 220c
and are kept for 5 days
• Refractoriness is caused by HLA allo
immunization or non immune sepsis
hyper splenism
• Matching of blood type is not
mandatory
Relative contra indications for platelets
Fresh frozen ‫פלסמה קפואה‬
plasma FFP
• Frozen within 6h from collections
• Indications for use in coagulation
factors deficiency (Massive
bleeding Hepatic failure DIC
Disseminated intravascular
coagulation)
• Volume of 200 –250 cc kept at 20°c for a year period
• Given according to type but not
crossed
Cryopercipitate
• Plasma is frozen at –80 0c, thawed at 40c
and then separated from plasma and kept
at –200c for up to 1 year
• Contain factor viii and fibrinogen
• Use at DIC low fibrinogen and for
hemophilia A and von Willebrand’s
disease
• Cryo supernatant (cryo poor plasma) is
used for apharesis in TTP patients
Left:
Freezer filled with
FFP and Cryo.
Upper Right:
Refrigerator with
bags of RBCs.
Lower Right:
Platelet Storage.
ew of Machupichu
a pichu
Transfusion Transmitted
Diseases
Select safe donors
Serial testing
Viral-inactive procedures
Control unnecessary use of blood
products
Transfusion 43:787 Lee DH Mehta MD
Classification of Tx Reactions
Acute R with Fever •
IHA (ABO incompatible) less –
common
FNHTR common
Bacterial Contamination less –Delayed R with Fever
common
DHA common
Acute R without Fever •
TA-GVHD less common
Urticarial TR common –
Circulation Overload less –
common
Anaphylaxis less common – Delayed R without
Fever
TRALI less common –
Post-transfusion Purpura
Iron Overload
Work out Transfusion
Reactions
Cross Match
Direct Antiglobulin Test
Antibody Screen
Blood Culture
Acute Reaction with Fever
Febrile Non hemolytic TR
Bacterial Contamination
IHA (ABO incompatible)
Febrile Non hemolytic TRs
• Most frequently reported reactions, 1-1.5%
• Increase in temperature 10C or 2 0F with no
other explanation
• Signs/Symptoms: Fever & chills (no rigors),
Headache, Flushing , Rapid pulse, Nausea,
vomiting , Shortness of breath
• Lab findings: Nothing
Febrile Nonhemolytic TRs
Cytokines released by donor WBC
Cytokines released after transfusion
(donor anti-HLA antibodies)
Recipient macrophages release
cytokines
More common with random
platelets
Use pre-storage leukoreduced blood
components
Cytokines in FNTR
IL 1: Causes fever by production of PG E2
IL1
IL6
TNF
TNF
IL6 Central mediators of inflammation
IL1
IL8
Febrile Reaction: Thresholds
5 x108 WBC per unit will cause FNTR
5 x 106 WBC per unit will cause HLA sensitization
‫דם מסונן‬
‫• הסינון ע"י פילטר מסוג‬
‫‪Leukostop‬‬
‫• להורדת כמות התאים הלבנים‬
‫במרכיב (כדוריות או‬
‫טסיות)לערך נמוך מ‪5X 106‬‬
‫למניעת תגובות כתוצאה‬
‫מיצירת נוגדנים כנגד תאים‬
‫לבנים במטופלים שמקבלים‬
‫מרכיבי דם במהלך תקופה‬
‫ארוכה‬
‫• למניעת הדבקה ב‪CMV-‬‬
FNTR
• Most common in :
- Women (2:1)
- Multiply transfused patients
• Rare in children
Bacterial Contamination (Septic TR)
At the time of phlebotomy, components
preparation, during storage, thawing in
water-baths.
Yersinia enterocolitica, Citrobacter
freundii, E. coli, Pseudomonas
Grow in low temp, Produce endotoxin
Dark brown color
Incidence 1:3000 mainly in platelets
concentrations
Bacterial Contamination (Septic TR)
symptoms
Rapid high fever with flushing and
dryness of skin
Rigors
Abdominal cramping
Nausea & vomiting
Shock
Bacterial Contamination (Septic TR)
Laboratory findings:
Discolored product
Hemoglobinemia and hemoglobinuria
DAT negative
Gram stain is unreliable
Bacterial culture is positive
Rx:
Immediate iv antibiotics (broad-spectrum)
Therapy for shock (fluid support,
dopamine, steroids)
Immediate Hemolytic TR (ABO)
ABO incompatibility
Clerical errors
Disastrous, often fatal
Intravascular (ABO)
extravascular (others)
Intravascular Hemolysis
Red Blood Cell Lysis as seen by
transmission
Electron Microscope.
(From Rossi E. “Principles of
Transfusion Medicine” 2nd Edition)
Immediate Hemolytic TR (ABO)
Signs & Symptoms
Fever and chills
Pain in the back or at infusion site
Hypotension/Shock
DIC/Bleeding (important in anesthetized
patients)
Immediate Hemolytic TR (ABO)
Lab findings
Pink or red serum
DAT positive (unless all donor cells are destroyed)
Elevated bilirubin
Hemoglobinemia/hemoglobinuria
Lab finding of DIC (PT, aPTT, DD)
RBC abnormalities (schistocytes/spherocytes)
Rx:Support volume ,Maintain urine output
Treat DIC
Acute TR without Fever
Urticarial TR
Circulation Overload
Anaphylaxis
TRALI
Urticarial TR
Second most frequently reported •
reaction
Localized rash and edema •
Mechanism •
Hypersensitivity to plasma –
proteins/mast cells release histamine
Prevention and treatment •
Benadryl 25-50mg –
“Washed” blood components –
Urticarial TR
• Second most frequently
reported reaction
• Mechanism
– Hypersensitivity to
– plasma proteins
• Prevention
– “Washed” blood
components
Anaphylactic TR
Classic story: IgA deficient Pt got •
IgA-containing products
IgA deficient 1/700, Anaphylactic •
TRs 1/20,000.
Anaphylactic shock within the first •
few drops of transfusion
Anaphylactic TR
Mechanism •
Hypersensitivity to plasma proteins –
Prevention •
No plasma transfusion –
Washed RBC, Platelets –
Treatment •
Epinephrine 1:1000, subcut; 1:10,000 iv –
inf
Transfusion-Related Acute Lung
Injury - TRALI
Rare, may occasionally be febrile •
Mechanism •
Donor’s anti-WBC/HLA antibodies –
WBC micro-aggregates in pulmonary –
microcirculation
Clinically identical to ARDS, but •
resolves in 12-24 hours
FEBRILE NON HEMOLYTIC TRANSFUSION REACTION
Klein HG ASH 1998
T.R.A.L.I.
Clumps of WBC form and get trapped in the
pulmonary microcirculation.
Delayed Hemolytic Anemia
The third most common TRs
Hemolysis occurs several days to
weeks after transfusion
Usually extravascular hemolysis
Kidd (Jka), Duffy, Kell
Signs & Symptoms : Often none
Fever, Anemia, Mild jaundice
Hemolytic Transfusion Reactions
Extravascular Hemolysis
RBC phagocytosis as seen by TEM
(From Rossi E. “Principles of Transfusion Medicine” 2nd Edition)
Delayed Hemolytic Anemia
Lab findings : DAT positive
Anemia,
Positive antibody screen
Treatment: Usually not necessary
If severe treat like acute hemolysis
Transfusion AssociatedGVHD
Mechanism
Donor,s cytotoxic lymphocytes attack
recipient's stem cells
Getting blood from first-degree relative
Usually when “warm blood” is given and not
irradiated
Patients at risk:
Marrow or stem cell transplant recipients
Congenital T-cell deficient Pts (DiGeorge,s)
Neonatal/intrauterine transfusions
Hodgkin,s disease
TA-GVHD
Bone marrow transplant patients
Immunocompromised patients
Neonatal patients
Hodgkin’s
Develop 1-2 weeks after transfusion
Rash, diffuse mucositis, hepatitis
Pancytopenia, infection, bleeding
Hypoplastic/aplastic bone marrow failure
Fetal in 90% of cases, even with treatment
‫דם מוקרן‬
‫• ההקרנה מונעת פעילות‬
‫התאים הלבנים ע"י פגיעה‬
‫בחומר התורשתי שלהם‬
‫• למניעת תגובת דחיה של‬
‫המטופל ע"י הכדוריות הלבנות‬
‫מהמנה (‪ )GVHD‬במטופלים‬
‫בעלי מערכת חיסון פגועה‬
‫(למשל אחרי טיפול כימותרפי)‬
‫• במקרים כאלה יינתנו כדוריות‬
‫וטסיות מוקרנות‬
Infectious risks of Blood
Transfusion
Viral Infection
Hepatitis A
Hepatitis B
Hepatitis C
HIV
HTLV I/II
Parvovirus B19
Estimated Risk Death/106 Units
1/106
1:30-250000
1:30-150000
1:2x105-106
1: 250000 – 2x106
1:10000
0
0-0.14
0.5-17
0.5-5
0
0
1:500000
1:12000
0.1-0.25
21
Bacterial infection
Red Cells
Platelets
NEJM, Feb 18, 525-533,1999
Figure 1. New test implementation and declining risk of viral infections from transfusion
Hillyer, C. D. et al. Hematology 2003;2003:575-589
Copyright ©2003 American Society of Hematology. Copyright restrictions may apply.
Post Transfusion Hepatitis
 Jaundice and LFT abnormalities following
blood transfusion
 1968 Post Transfusion hepatitis HBV related
 NANB - PTH
 NANBNC” -PTH”
Hepatitis C
 Transmission
Infected needles
Blood transfusion
Surgical/ Endoscopic procedures
 Prevention
Questionnaire
anti-HCV - 1991
HCV -RNA
HCV -Ag (experimental)
ALT, anti-HBc - Surrogate Tests
HCV Markers During Early Infection
HCV RNA
HCV Ag
0
10
20
30
40
50 60
Days
HCV RNA
HCV antibody
70
Day 12
Day 70
Anti-HCV
80
90 100
58 Days
Hepatitis B transmission prevention
 Questionnaire
 HBsAg testing
 Anti-HBc – some countries
 HBV DNA - IND
HBV Markers During Early Infection
HBV DNA
Anti- HBc
HBsAg
ALT
‫חלון אנטיגני וסרולוגי‬
‫בדיקה מולקולרית חיובית‬
1:400000‫ב‬
0
10
20
HBV DNA
HBsAg
30
40
50
60 70
Days
80
90 100 110 120
up to 23 days prior to HBsAg
Day 56; disappears day 120
TA - HIV
HIV Markers During Early Infection
Anti-HIV
HIV RNA
(plasma)
11
0
10
HIV p24
antigen
16 22
20
30
40
50 60
Days
HIV RNA
HIV p24 Ag
HIV antibody
70
Day 11
Day 16
Day 22
80
90 100
11 Days
HIV - prevention of
transmission by blood products

Blood donor education
 Questionnaire
 Tests for HIV
HIV -Ab, Elisa
p24Ag, Elisa
HIV RNA
IND
Human T Lymphotrophic Virus
I/II
 RNA Virus - Present in T lymphocytes
 Morbidity ATL - Adult T Cell leukemia
TSP - Tropical Spastic Paraparesis
HAM - HTLV associated myelopathy
appears in 2-4% of carriers after >20
years
Human T Lymphotrophic Virus
I/II
Transmission modes
Endemic countries:
Japan, Carribean, South America
Breast feeding, Sex , Blood transfusion
Other Regions
Blood Products, Infected needles
(HTLV II)
Transfusion Associated
Viral Hepatitis, USA
% Recipients
infected
Years of Transfusion
Cytomegalovirus = CMV
 Most common virus transmitted by blood
transfusion
 Morbidity
Infectious Mononucleosis
Immunosupressed +
Retinitis, Gastritis, Nephritis, Rash
Graft rejection, Pancytopenia, Etc.
Cytomegalovirus = CMV
 Transmission by Lym in cellular products
 Risk groups
Neonate <1500 Gr, Mother CMV neg
Transplanted Pt. CMV neg, Donor Pos
Pregnant women CMV neg
AIDS pts CMV neg
 Prevention - CMV Ab neg blood
Leukoreduction
Mad cows and Blood
 BSE = Bovine Spongiform Encephalitis
 21.3.96 - Possible transmission to humans
10 cases nvCJD
young
short incubation period
Brain changes similar to CJD
 ? Species barrier
 ?? Transmission by blood and
blood products
Parvovirus B19
 DNA Virus
Transmission during viremia
Does not cause chronic infection
 Morbidity
Children Fifth Disease ,
Erythema Infectiousum
Aplastic Crisis - Chronic Hemolytic
anemias
- AIDS
 Prevention- No routine screening for donations
PCR 1:3300 units Positive
Malaria
 > 250 millions acquired Malaria
 Chronic infection of Red Cells
 Morbidity - Parasite dependent
USA - 3/ Cases year Transfusion realated
Prevention of transmission by blood :
No good test available for donor screening
Residents of endemic areas/Acquired Malaria
Avoid donations 3 years
Travel to endemic area
Avoid donations 1 year
Chagas’ Disease
Causative Agent Trypanosoma Cruzi
Transmitted by Mosquitos
Transfusion Transmission significant in
immunosupressed
 Endemic in central and south America
Bolivia 62% population - exposed
 Morbidity
Prolonged asymptomatic stage
Cardiomyopathy
 Prevention
No effective test for donor screening
Infectious markers tests in
Israel
anti-HIV I/II 
HBsAg 
anti-HCV 
anti-HTLV I/II 
TPHA 
ALT 
NAT Reduction - Window Period
Virus
Infection to
Ab detection
Infection to
NAT detection
Reduction by
NAT testing
HIV
22 days
11 days
50%
HCV
70 days
12 days
83%
HBV
56 days
33-41 days
27-41%
APHERESIS
APHERESIS
Therapeutic apheresis
TPE – therapeutic plasma exchange
cholesterol reduction, immunoglobulins
)TTP ,myasthenia gravis
Leukodeplition, thrombodeplition
Photopheresis
‫פרזיס לתרומות‬
‫•‬
‫•‬
‫•‬
‫•‬
‫איסוף תאי אב‬
‫‪Single donor platelets‬‬
‫גרנולוציטים‬
‫דם מלא מופרד‬
‫‪Single Donor Platelets‬‬
‫• טסיות מתורם יחיד‬
‫המופקות בתהליך של‬
‫אפרזיס ‪3X 1011‬‬
‫• יינתנו למטופלים שספירת‬
‫הטסיות שלהם לא עולה‬
‫לאחר מתן תרכיז טסיות‬
‫רגילאו חולים עם תופעות‬
‫לואי קשות‪ .‬אפשרות נוספת‬
‫•‬
‫‪FILTERED POOL WITHIN 2‬‬
‫‪DAYS of STORAGE‬‬
‫פרזיס טיפולי‬
TPE – therapeutic plasma exchange •
)TTP ,‫ נוגדנים‬,‫(כולסטרול‬
Leukodeplition, thrombodeplition •
Photopheresis •