Download JOINT PROGRAM IN TRANSFUSION MEDICINE

1
JOINT PROGRAM
IN
TRANSFUSION MEDICINE
HOUSESTAFF MANUAL
(Revised 10/2009)
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CONTENTS
1. Overview of BWH/CHB/DFCI Transfusion Service
1.2 Weekly schedule
1.3 Policy for Resident/Fellow Supervision
1.4 Fellowship Duty Hours Policy
1.5 Resident/Fellow Responsibilities: Apheresis Service
1.6 Educational Objectives
1.7 Curriculum
1.8 Handoff Policy
2. BWH Blood Bank
2.1 Pretransfusion compatibility testing
2.2Antibody identification
2.3 Component usage guidelines
2.3.1 RBCs
2.3.2 Platelets
2.3.3 FFP
2.3.4 Cryoprecipitate
2.3.5 Clotting Factor Concentrates
2.3.6 Granulocytes
2.3.7 SOPs for administration of Blood Products
2.4 Transfusion reactions
2.5 RhIg administration
3. BWH Blood Donor Center
3.1 Therapeutic apheresis
3.1.1 Indications
3.1.2 Venous access
3.1.3 Adverse reactions
3.2 Whole blood donation
3.2.1 Allogeneic donors
3.2.2 Autologous donors
3.2.3 Adverse reactions
4. DFCI Kraft Family Blood Donor Center
4.1 Apheresis platelet donation
4.2 Peripheral blood stem cell collection
5. Children's Hospital, Boston
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1. OVERVIEW OF THE BWH/DFCI/CHB TRANSFUSION SERVICE
1.2
WEEKLY SCHEDULE
MONDAY
1500 Work
Rounds
TUESDAY
0900 Serology
WEDNESDAY
THURSDAY
0800 GrossMicro
FRIDAY
0815 CHB
Heme conf
1300 BWH
Heme Conf
1200 Fellows
Conf
1500 Work
Rounds
1500 Work
Rounds
1200 BMT
Grand Rounds
1300 CP Conf
1500 Work
Rounds
1500 Work
Rounds
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1.3
JPTM POLICY FOR RESIDENT AND FELLOW SUPERVISION
Consults
Rotating residents and fellows are responsible for the initial evaluation of consults, including transfusion
reactions, serologic workups, and therapeutic apheresis procedures. All formal consults will be discussed
with and signed off by the supervising attending physician.
Other clinical issues
Residents and fellows evaluate a variety of clinical issues e.g. questions regarding blood donation, blood
component utilization, management of apheresis patients, etc. Critical patient issues should be presented
in a timely fashion to the on-call attending. Residents/fellows can never be criticized for calling the
attending.
Attending physician backup
Attending physician backup will be available at all times. If a resident/fellow is unable to reach the oncall attending during an emergency, one of the off-service JPTM attending physicians should be called for
backup.
Kraft Family Blood Donor Center: medical coverage
In addition to the blood bank attending, medical backup is available through the “Doc of the Day”
(rotating DFCI attending MD) as well as the DFCI code team.
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1.4
DUTY HOURS POLICY*
HARVARD MEDICAL SCHOOL FELLOWSHIP PROGRAM
IN TRANSFUSION MEDICINE

Transfusion Medicine Fellow duty hours are herein defined as time spent at the worksite
performing clinical and/or academic activities required by the resident’s GME training program,
including:
o Patient care activities, both inpatient and ambulatory, whether scheduled or not (i.e.,
includes time spent in the hospital when a resident is called in from home)
o Administrative activities that are related to patient care.
o In-hospital “on-call”, regardless of what the resident activities are during such periods
scheduled- academic activities (i.e., conferences and other didactics).

The Joint Program in Transfusion Medicine endorses the duty hour and on-call limits defined by
the ACGME (paraphrased below in italics).
o Fellows must not be assigned duty hours in excess of 80 hours per week, averaged over a
four-week period.
o Fellows must be provided with at least one day off in seven. Note: A day off is defined as
a continuous 24 hour period free from assigned educational and clinical responsibilities,
including offsite beeper call, rounds and conferences. JPTM attending physicians will take
“first call” from Sunday at 8:00 am until Monday at 8:00 am as needed to ensure that the
one day off in seven is provided.
o Fellows must not be assigned in-house call any more often then every third night,
averaged over a four-week period. Note: This excludes beeper call from home and/or
academic preparatory work that is or could be done offsite.
o Fellows should have at least 10 hours off between regularly scheduled on-site duty shifts
(including after in-house call).
o Fellows must not be scheduled to work in excess of 24 consecutive hours. This applies to
onsite work.
o
If a fellow experiences an unexpected illness or if they are concerned that fatigue is
impairing their performance or a colleague’s performance, they must promptly notify their
attending, who will arrange for alternative coverage.
* also applies to Transfusion Medicine residents.

(Last Updated: June 7, 2005)
Backup coverage:
In the instance of an emergency procedure occurring in the evening prior to a normal weekday
shift, the resident or fellow responsible for the procedure must assess the likelihood that he or she
will violate the ACGME duty hours guidelines, above. If, in the resident or fellow's judgment,
such a violation will occur, the resident or fellow must (1) inform his or her attending physician
and (2) transfer coverage of the beeper to the appropriate backup MD (defined below) the next
morning at 8 am at the latest. The "relief" resident or fellow must take over all patient care duties
at 8:00 AM, and the "relieved" resident or fellow will be excused from duty until at least 10 hours
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following his or her departure from the hospital, though small deviations from this 10-hour
minimum are allowable under ACGME rules, and may be preferable to short-duration pager
transfers.

Backup MD:
If there are two fully-trained residents on the service, the off-call resident is expected to provide
coverage. If there is one fully-trained resident on the service, the fellow is expected to provide
coverage. If the fellow is on-call and there is a fully-trained resident on the service, the resident is
expected to provide coverage. If no covering resident or fellow is available, the attending will be
expected to cover or to work with the CP chief resident to identify a qualified backup MD.
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1.5
APHERESIS SERVICE: RESIDENT/FELLOW RESPONSIBILITIES
Outpatient Responsibilities:
BWH: Photopheresis and plasmapheresis patients in the blood donor center (732-7524)
All morning patients should be seen and examined by 10:00am.
All afternoon patients should be seen and examined by 2pm.
If a new patient is scheduled to arrive and need to be consented before starting the
procedure, one of the team should plan to be in the blood donor center within 10 minutes of the patient
arriving so the procedure is not delayed.
DFCI: All stem cell harvest patients should be seen and examined by 11:00am at the Kraft Donor
Center (632-6260).
CHB: Call to the in the morning or check the weekly calendar in the pheresis unit (355-6270) to
determine if there are Children's Hospital, Boston outpatients to be seen.
Inpatient Responsibilities:
BWH: If you do not know the time of the scheduled procedure for an inpatient, check with the
nurses in the donor center (732-7524) to determine the time for the procedure and whether the patient will
need to be seen, evaluated and orders written before the nurses can start the procedure. In general, all
NEW or potentially UNSTABLE patients need to be seen and examined prior to start of the procedure.
CHB: Check with the nurses to determine the time of the scheduled procedure. Same as above.
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BETH ISRAEL
DEACONESS MEDICAL
CENTER
1.6
BRIGHAM AND
WOMEN'S HOSPITAL
CHILDREN’S HOSPITAL,
BOSTON
DANA FARBER
CANCER INSTITUTE
MASSACHUSETTS
GENERAL HOSPITAL
HARVARD MEDICAL
SCHOOL
EDUCATIONAL OBJECTIVES
HARVARD MEDICAL SCHOOL
FELLOWSHIP PROGRAM IN TRANSFUSION MEDICINE
EDUCATIONAL OBJECTIVES AND APPROACHES
Updated 7/1/06
The HMS Fellowship Program in Transfusion Medicine emphasizes the achievement of key
competencies by its clinical fellows. Objectives and approaches are summarized below for the six
major areas of importance:
I. PATIENT CARE
Objectives –
 To gain diagnostic competence and the ability to provide appropriate and effective pathology
services and clinical consultation.
 To learn to collaborate with other professionals, include those in other disciplines, in providing
patient-focused care.
 To learn the principles of compassionate and cost-effective patient care.




Approach Fellows gather essential and accurate clinical information about the patients on whom they perform
consultations regarding therapeutic apheresis, transfusion reactions, serologic workups, hemostasis, or
other transfusion-related issues.
Fellows make informed decisions regarding the diagnostic workup of blood bank serologic specimens
based on patients' clinical history, up-to-date scientific evidence gleaned from journal articles,
internet-based searches, textbooks, and clinical judgment.
Fellows use available information technology (hospital and laboratory information systems, electronic
bibliographic searches and journals) to support workup and diagnosis, and to help educate clinicians
by providing relevant literature references.
Fellows demonstrate competence in the performance of tasks considered essential for transfusion
medicine practice, including:
 Providing guidance to the various clinical services on laboratory testing and blood product usage,
including coagulation factors.
 Planning and medical oversight of therapeutic apheresis procedures.
 Performing transfusion reaction investigations with appropriate follow up to the clinical services.
 Evaluating and managing blood and peripheral blood stem cell donors.
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II. MEDICAL KNOWLEDGE
Objectives –
 To gather and consolidate knowledge about established and evolving basic biological and
clinical sciences and clinicopathologic correlations, and the application of this information to
patient care and to pathology.
 To gain analytical and problem-solving skills and their application in pathology.
Approach  Fellows demonstrate an investigatory and analytical thinking approach to clinical situations dependent
on the blood bank/transfusion service including:
 Performing thoughtful and accurate serologic and transfusion reaction workups.
 Suggesting appropriate additional testing (e.g. advanced serologic testing serology, HLA
testing, etc.) if applicable.
 Formulating comprehensive and cohesive differential diagnoses and developing treatment
plans for patients in whom therapeutic apheresis is being considered.
 Designing and carrying out focused research projects, such as clinicopathologic studies, or
case reports with literature review.
 Fellows know and apply the basic and clinically supportive sciences which are appropriate to the
specialty of transfusion medicine, including:
 Demonstration of knowledge of hematology, immunology and infectious disease and as they apply to
transfusion medicine.

Demonstration of familiarity with all aspects of blood component manufacturing,
testing, storage and provision.

Demonstration of familiarity with blood group serology and blood bank testing
methods.

Demonstration of detailed knowledge of appropriate transfusion medicine practices as
applied to specific clinical areas such as surgery, hematology/oncology, hematopoietic stem
cell transplantation, pediatrics, obstetrics, etc.

Demonstration of understanding the principles of therapeutic apheresis, and the
rationale for using apheresis in a variety of disease states.
III. PRACTICE-BASED LEARNING AND IMPROVEMENT

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
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Objectives –
To gain the ability to evaluate and improve a diagnostic and consultative practice based on
scientific evidence.
To locate, appraise and use scientific data to improve patient care.
To apply knowledge of rigorous scientific principles, study design and statistical methods to
evaluate published clinical studies and do clinicopathologic investigation.
To learn to use information technology to manage information and conduct personal continuing
education.
To facilitate the learning of students, residents, colleagues and other health care professionals.
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


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Approach Fellows show the ability to analyze practice experience and perform practice-based improvement
activities using a systematic methodology, including:

Active participation in weekly didactic conferences and operational meetings (e.g.
BWH/DFCI Biological Therapies Committee).

Participation in quality monitoring efforts e.g. assisting with quarterly transfusion
appropriateness audits.
Fellows show ability to locate, appraise, and assimilate evidence from scientific studies related to
patients' health care problems, including using literature search and review to find relevant scientific
references to aid in performing laboratory and clinical consultations.
Fellows are able to apply knowledge of study designs and statistical methods to the appraisal of
clinical studies and other information on diagnostic and therapeutic effectiveness, including:

Active participation in weekly conferences with critical discussion of study designs and
statistical methods of presented articles.

Design and conduct independent clinical, translational or basic research studies.
Fellows demonstrate competency in the use of information technology to manage information, access
on-line medical information, and support their own education, including:
 Accessing of patient clinical information and previous laboratory results via the hospital's
Laboratory Information System.
 Performance of computer bibliographic searches.
Fellows actively participate in the teaching of medical students and other health care professionals,
including:
 Teaching students on elective rotations in Pathology and in Medical school courses as laboratory
instructors.
 Teaching students and fellows from other disciplines during in-hospital clinical conferences.
 Teaching laboratory and donor center staff.
IV. INTERPERSONAL AND COMMUNICATION SKILLS




Objectives –
To acquire and use interpersonal and communication skills that result in effective information
exchange and collaboration with other health care professionals and patients (and their
families).
To create and maintain an effective, ethically sound and respectful relationship with peers,
other health care professionals, and patients (and their families).
To use effective listening skills.
To work effectively with other professional and non-professional staff.
Approach  Fellows demonstrate effective listening skills and elicit and provide information using effective
nonverbal, explanatory, questioning and writing skills. This includes:

Following instructions from attending physicians during performance of consultations and
management of therapeutic apheresis patients and donors.

Demonstrating interest in case material during teaching rounds by asking relevant questions,
and responding articulately to questions from transfusion medicine attendings.
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
Eliciting relevant clinical information from and providing appropriate diagnostic information
and clinical advice to clinicians via telephone conversations.

Generating concise, accurate, and complete consultations in the clinical laboratories.

Demonstrating effective oral and written communication skills in didactic talks and research
projects.
 Fellows should work effectively with others as a member or leader of health care team or other
professional group, including participation with other members of the Dept. of Pathology and
Laboratory Medicine and other departments on various hospital committees.
V. PROFESSIONALISM

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

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


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

Objectives –
To maintain a commitment to excellence in carrying out professional responsibilities, adherence
to ethical principles, and sensitivity to diversity in the workplace.
To maintain respect, compassion and integrity; responsiveness to patients that supercedes selfinterest; accountability to patients, colleagues, and the profession and discipline of pathology;
and a commitment to on-going professional development.
To develop and maintain a commitment to confidentiality of patient information, informed
consent and ethical business practices.
To learn the highest principles relating to conflict of interest and commitment.
To develop the maximum sensitivity to colleague and patient ethnicity, age, gender and
disabilities.
Approach Fellows must demonstrate a commitment to carrying out professional responsibilities, adherence to
ethical principles, and sensitivity to a diverse patient population, including:
Showing respect, compassion, and integrity during interactions with patients.
Showing responsiveness and accountability to the needs of patients and their families and clinicians
that supersedes self-interest, including contributions to the timely completion of reports, and
discussion of results with clinicians.
Demonstrating commitment to excellence and ongoing professional development, such as completing
directed and independent reading from pathology textbooks and journal articles, designing and
completing research projects, undertaking literature searches on various transfusion medicine topics,
providing high-quality presentations at conferences, and attending in-house and off -site pathology
lectures and conferences.
Demonstrating a commitment to ethical principles pertaining to confidentiality of donor and patient
information.
Demonstrating commitment to ethical principles pertaining to business practices, including helping to
ensure accurate billing for services.
Demonstrating adherence to the highest principles of mutual respect of colleagues and support
personnel.
VI. SYSTEMS-BASED PRACTICE
Objectives –
 To develop an awareness of and responsiveness to the larger context and system of health care
and the ability to access and effectively use resources to provide value-added pathology services.
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 To understand how pathology services affects other health care professionals, organizations and
systems.
 To develop an understanding of the principles of cost-effective health care and resource
allocation that enhances (and does not compromise) quality of service and patient care.
Approach  Fellows must demonstrate an awareness of and responsiveness to the larger context and system of
health care and the ability to effectively call on system resources to provide care that is of optimal
value. This includes:
 Gaining an appreciation for transfusion medicine as a public health practice, and participating in
policy discussions and decision-making.
 Demonstrating knowledge of methods for controlling health care costs and allocation of resources.
 Practicing cost-effective health care and resource (e.g. blood product) allocation that does not
compromise the quality of care.
Demonstrating knowledge of how to partner with health care managers and health care providers to
assess, coordinate, and improve health care, and knowledge of how these activities can affect system
performance.
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BETH ISRAEL
DEACONESS MEDICAL
CENTER
1.7
BRIGHAM AND
WOMEN'S HOSPITAL
CHILDREN’S HOSPITAL,
BOSTON
DANA FARBER
CANCER INSTITUTE
MASSACHUSETTS
GENERAL HOSPITAL
HARVARD MEDICAL
SCHOOL
CURRICULUM
CORE CURRICULUM
HARVARD MEDICAL SCHOOL
FELLOWSHIP PROGRAM IN TRANSFUSION MEDICINE
Updated 9/1/05
Upon completion of clinical training, fellows are expected to demonstrate understanding of the following
aspects of Transfusion Medicine, organized by Competency:
I. PATIENT CARE
A. Blood Donation
1. Criteria for acceptability of individuals for blood donation
2. Process of donor interview, arm inspection and physical examination
3. Presentation and management of complications of blood donation
4. Clinical significance of product storage lesions
B. Blood Group Serology/Biochemistry
1. Clinically significant vs. insignificant red cell alloantibodies
a) Serologic specificity
b) Isotype
c) Thermal amplitude
2. Direct Antiglobulin Test in evaluating:
a) transfusion reaction
b) hemolytic disease of the newborn
c) autoimmune hemolytic anemia
d) drug induced hemolytic anemia
C. Blood Transfusion Practices
1. Clinical indications and dose/response for transfusion of:
a) Packed Red Blood Cells
b) Fresh Frozen Plasma
c) Cryoprecipitate
d) Platelets
e) Granulocytes
f) Coagulation factors
(1) FVIII
(2) FIX
(3) Prothrombin Complex Concentrates (FEIBA, Autoplex)
(4) rFVIIa (NovoSeven)
(5) Humate P for von Willebrand Disease
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g) RhIg
h) Other plasma derivatives e.g. albumin, IVIg, etc.
2. Product administration
a) infusion rate
b) time to expiration after pooling or preparation
3. CMV-safe blood products: indications and methods
4. Leukoreduction: indications and methods
5. Irradiated blood products: indications and methods
6. Compatibility testing requirements
a) ABO/Rh
b) Antibody screen
c) Abbreviated v. full crossmatch
7. Emergency transfusion protocols
8. Massive transfusion
a) metabolic abnormalities
b) dilutional coagulopathy
c) hypothermia
9. Autoimmune hemolytic anemia (AIHA)
a) Classes
(1) Warm AIHA
(2) Cold AIHA
(3) Paroxysmal Cold Hemoglobinuria
(4) Atypical AIHA
(a) DAT-negative AIHA
(b) Combined warm + cold AIHA
b) Pathophysiology
c) Clinical presentation
d) Laboratory evaluation
e) Selection of blood for transfusion
10. Inventory management during shortages
D. Adverse Effects of Blood Transfusion
1. Noninfectious complications of transfusion: presentation, pathophysiology, differential
diagnosis, laboratory workup, management and prevention of:
a) Immune-mediated transfusion reactions
(1) Hemolytic reactions
(a) Acute
(b) Delayed
(2) Febrile Nonhemolytic Transfusion Reaction
(3) Allergic
(4) Urticarial
(5) Anaphylactic
(6) Transfusion-Related Acute Lung Injury (TRALI)
(7) Transfusion-associated graft-versus-host disease
(8) Post-transfusion purpura
b) Non-immune mediated transfusion reactions
(1) Volume overload
(2) Hypotensive reaction
(3) Citrate toxicity
(4) Hyperkalemia
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(5) Hypothermia
(6) Nonimmune hemolysis (hypotonic solutions, pumps, etc.)
2. Infectious complications of transfusion: disease associations, significance, Incidence,
per unit risk, pathophysiology, signs/symptoms, prevention, donor screening, management
of:
a) Viral infections
(1) Hepatitis B Virus
(2) Hepatitis C Virus
(3) HIV I/II
(4) HTLV I/II
(5) West Nile Virus
(6) CMV
(7) EBV
b) Bacterial infections
c) Parasitic infections
(1) Syphilis
(2) Malaria
(3) Babesia
(4) Chagas Disease
d) Prion diseases
(1) Creutzfeldt-Jakob Disease
(2) Variant Creutzfeldt-Jakob Disease
E. Apheresis: indications, anticoagulation, timing of procedures, replacement fluids, venous
access, recognition and management of adverse events for:
1. Component collection
a) Platelets
b) Red cells
c) Granulocytes
d) Plasma
2. Therapeutic Apheresis procedures
a) Plasma Exchange
b) Red Cell Exchange
c) Leukoreduction
d) Red Cell Depletion
e) LDL apheresis (Liposorber)
f) Photopheresis
3. Peripheral Blood Stem Cell collections
II. MEDICAL KNOWLEDGE
A. Blood Donation
1. Laboratory tests performed on donated blood.
2. Methodology, and sensitivity/specificity of infectious disease markers
3. Donor deferral criteria
4. Deferred donor registry
B. Blood Component Manufacturing and Storage
1. Preparation of blood components from whole blood
2. Products that may be collected using hemapheresis procedures
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3.
4.
5.
6.
7.
8.
Blood product anticoagulant/preservatives
Storage conditions/expiration dates for each blood component.
Preparation of components which require pooling/thawing
Special processing techniques of leukoreduction/washing/volume reduction/irradiation
Metabolic changes that occur during storage
Plasma derivatives that are prepared commercially
C. Blood Transfusion Practice
1. Transfusion “triggers”
a) Red cell
b) Platelet
c) Plasma
2. Refractoriness to platelet transfusion
3. Blood conservation strategies
4. Pediatric transfusion practice
5. Neonatal transfusion practice
6. Surgical transfusion support
D. Blood Group Serology/Biochemistry
1. Immunologic principles
a) Immunoglobulin structure and genetic basis for antibody diversity
b) Red cell alloantibodies vs. red cell autoantibodies
c) Primary and secondary immune responses to red cell antigens
d) “Naturally occurring” antibodies vs those requiring prior immunization
e) Mechanisms of red cell sensitization
f) Mechanisms of red cell destruction
(1) Complement activation
(2) Intravascular vs extravascular immune hemolysis
2. Red cell blood group antigens: biochemistry, genetic inheritance, immunogenicity,
clinical significance, common phenotypes of:
a) Carbohydrate blood group antigens
(1) ABH
(2) Lewis
(3) P
(4) I/i
b) Protein blood group antigens
(1) Rh
(2) Kell
(3) Duffy
(4) Kidd
(5) MNS
c) High frequency antigens
d) Low frequency antigens
3. Disease associations with the “null” phenotypes for ABO, Rh, Kell
4. Serologic Testing
a) Parameters affecting in vitro detection of antigen-antibody reactions
b) Testing formats
(1) Tube
(2) Gel
(3) Solid phase
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c) Indications, reagents, methods and interpretation of:
(1) ABO/RhD typing
(2) Weak D testing
(3) Antibody screen
(4) Antibody panel identification
(5) Crossmatching Tests
(a) Abbreviated
(b) Full
(6) Enhancement techniques
(a) Enzymes
(b) LISS, PEG
(7) Adsorption techniques
(a) Autologous
(b) Heterologous
(8) Elution techniques
(9) Neutralizaton techniques
(a)
(10) Direct Antiglobulin Test (DAT)
(11) Donath-Landsteiner Test
(12) Hemolytic Disease of the Newborn
(a) Rosette Test
(b) Kleihauer-Betke Test
(c) Antibody Titration Studies
(13) Electronic crossmatching
(a) Information system requirements
(b) Procedural requirements
(c) Advantages/disadvantages
5. Hematopoietic Stem Cell Transplantation
a) Diseases treated with stem cell transplantation
b) Stem cell biology
(1) Bone marrow-derived stem cells
(2) Peripheral blood stem cells
(3) Cord blood stem cells
c) Mobilization of stem cell donors
d) Stem Cell Collection
e) Stem Cell Processing
f) Thawing and Infusion
g) Engraftment
h) Transfusion support of stem cell transplantation patients
(1) Product support
(2) ABO mismatched transplants
(3) TA-GVHD
(4) CMV
6. HLA
a) Genetics
b) Structure of the HLA complex, Biochemistry
c) Clinical relevance to transfusion medicine e.g. management of platelet
refractoriness
d) Testing methods
7. Therapeutic Apheresis
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a) Principles
b) Indications/rationale for use in:
(1) Hematologic diseases, e.g.:
(a) TTP
(b) Acute leukemia/hyperleukocytosis
(c) Hyperviscosity syndromes
(d) Sickle Cell Disease
(2) Neurologic diseases, e.g.:
(a) Cryoglobulinemia
(b) Myasthenia Gravis
(c) Guillain-Barre Syndrome
III.
PRACTICE-BASED LEARNING & IMPROVEMENT
A. Application of current Transfusion Medicine literature to clinical decisions
B. Mastery of available information technology resources
C. Education of students, residents, techs
IV.
INTERPERSONAL AND COMMUNICATION SKILLS
A. Development of therapeutic relationships with patients
B. Foster effective working relationships with MDs and technical staff
C. Provide effective consultation to physicians from other services
V.
PROFESSIONALISM
A. Competent, conscientious, ethically sound practice
B. Sensitivity to culture, gender, age issues
VI.
SYSTEMS-BASED PRACTICE
A.
B.
C.
D.
E.
F.
G.
H.
I.
J.
K.
Prospective, concurrent and retrospective auditing of blood product transfusion
Hospital Transfusion Committees
Development of hospital transfusion policies
Roles of regulatory agencies whose oversight directly impacts Transfusion Service operation
1. FDA
2. AABB
3. JCAHO
4. FACT
5. DPH
Informed Consent for Transfusion
Crossmatch/Transfusion ratio
MSBOS ( Maximum surgical blood ordering schedule)
“Lookback”
Blood product inventory management
Budgeting
Blood bank information systems
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1.8
JOINT PROGRAM IN TRANSFUSION MEDICINE
POLICY FOR HANDOFFS AMONG RESIDENTS,
FELLOWS AND PHYSICAN ASSISTANTS

Each handoff must be an interactive communication between the outgoing and incoming caregiver that
should include both a written and verbal component. For Transfusion Medicine, this specifically
applies to:
o Any inpatient at BWH or CHB undergoing therapeutic apheresis
o Any inpatient or outpatient at CHB/BWH/DFCI actively receiving consultation by the
Transfusion Service
o Any significant laboratory issues at CHB/BWH/DFCI

Each handoff should be performed as a face-to-face interaction whenever possible. If a face-to-face
handoff is not feasible then it should occur via telephone. Email or voicemail by itself is not an
acceptable manner of handing off.

Handoffs should occur in a quiet, private place to minimize the possibility that information will be lost
or overheard by those other than the intended recipients.

Hand offs must include up to date information regarding the patient’s care including - patient
name, date of birth, MRN,bed location, admitting diagnosis, attending physician, current
condition, recent and anticipated changes in condition or treatment and plan of care.

Interruptions during hand offs must be limited to minimize the possibility that information would
fail to be conveyed.

Hand offs require a verification of the received information including a read back or repeat back of
critical components when appropriate.

The receiver of the hand off information must have an opportunity to review relevant patient
historical data, which may include previous care, treatment and services, and to ask all relevant
questions.
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2. BWH BLOOD BANK
One of the goals of the resident or fellow taking 1st call for the blood bank is to try to ensure that
transfused patients receive blood products appropriate to their clinical condition. You may be paged by
the blood bank if a patient receives an order for a blood product that falls outside of the norm (e.g., a
request for FFP in a patient with a normal PT.) Sometimes these “unusual” requests are perfectly
legitimate, sometimes they are not. Your role is to contact the clinical service, investigate the situation,
and make a judgement as to whether the request is medically sound. If a request for a product is truly not
indicated, try to offer an appropriate alternative. This may mean recommending not transfusing at all;
often the correct maneuver is to recommend transfusing something other than what was ordered. (e.g., a
bleeding patient with a platelet count of 25,000 and a normal PT/PTT needs platelets, not plasma.) You
should not refuse blood products; you should try to provide guidance to the primary service with the goal
of transfusing the patient appropriately. Many of these discussions will arise in the setting of patients
who are on the operating table, actively bleeding. Under these stressful circumstances, the surgeons
and/or anesthesiologists may begin ordering lots of blood products in an apparently haphazard fashion.
Find out what is happening from the anesthesiologist. It may be appropriate to ask him or her to follow
the patient’s labs to help guide transfusion decisions (e.g., ask to check a fibrinogen level before the next
dose of cryo is ordered).
21
2.1 Pretransfusion compatibility testing
Recommended reading: Technical Manual 13th Ed. pp. 375-388
When a new blood order is received for a patient, the blood bank initiates a serologic workup that
may take from 45 minutes-1 hour (the usual case) to several days (in cases of complicated/rare
“unexpected” antibodies.) In emergency situations, type O blood can be released without serologic
testing. The blood bank maintains “trauma coolers” stocked with 6 units of O+ and 2 units of O- PRBCs
available for immediate pickup by ED personnel. Refer to the chart below for typical blood turnaround
times.
BLOOD AVAILABILITY TIME TABLE
Time you can wait to
transfuse
5 minutes
RBC product available
Comments
Group O, uncrossmatched
15 minutes after sample
arrives in BB
ABO group-specific,
uncrossmatched
RBC antibodies found in
~1-3% of patients. Serious
hemolytic reactions rare.
Risks as above.
60 minutes after sample
arrives in BB
ABO group-specific,
crossmatched
2 hours-several hours;
rarely, longer
ABO group-specific,
antigen-negative
crossmatched in a pt. with
an “unexpected”
alloantibody.
No unexpected alloantibody
found. “Immediate spin”
crossmatch-compatible.
Some antibody
investigations may take
several hours. If blood is
absolutely required prior to
completion of workup, do
not withhold transfusion.
The clinical team should
confer with the blood bank
physician.
22
Standard pretransfusion testing for red cell transfusions includes the following:
1. ABO type. Recipient red cells are tested using anti-A and anti-B (“forward typing”); recipient
serum is tested against A1 and B cells (“reverse typing”).
2. Rh type. Recipient red cells are determined to be RhD positive or negative using anti-RhD.
3. Antibody screen. Recipient serum is screened for “unexpected” alloantibodies, using the
indirect antiglobulin test following a 37oC incubation (indirect Coomb’s). Two commercially
prepared, type O screening cells are used: I: Rh phenotype = R1R1; II: R2R2. The use of a third
screening cell (rr) is optional. This combination of screening cells covers the five most
important Rh group antigens, in addition to the other non-ABO antigens most commonly
encountered in clinical practice e.g. Jka/Jkb.
4. Immediate spin crossmatch. Saline-suspended donor cells are mixed with recipient serum at
room temperature, centrifuged immediately, and checked for (the absence of) agglutination.
The immediate spin crossmatch serves merely as a final check on ABO compatibility between
donor and recipient. An electronic crossmatch can be done instead of an immediate-spin
crossmatch, provided a properly validated computer system is in place that will reliably
prevent the release of ABO-mismatched units.
After completing the above testing, red cell units can be released provided that there are no ABO
discrepancies or unexpected antibodies in the serum. When ABO testing is discrepant (e.g. a patient
forward types as A but has anti-A in the serum) the discrepancy needs to be resolved. If transfusion
cannot be delayed, type O cells should be given as an interim measure.
Further testing is also required for patients with a demonstrated alloantibody in the serum (e.g. anti-E) or
patients with a history of an alloantibody. Note that over a 10-year period, some 50% of alloantibodies
stimulated by pregnancy or transfusion will become undetectable in the serum. It is important to give
antigen negative blood even when a previously detected alloantibody has faded, because a rapid
anamnestic response/hemolytic reaction can occur upon re-exposure to the antigen.
2.2 Antibody identification
Recommended reading: Technical Manual 13th Ed. pp. 389-418.
When a positive antibody screen is obtained, a panel of commercially prepared, phenotyped red
cells is tested against the patient’s serum using the indirect antiglobulin test. The antibody is identified
based on the pattern of reactivity observed, using the “cross-out” technique. To demonstrate convincingly
the presence of an alloantibody, it is necessary to identify three cells known to be positive for a given
antigen that yield a positive agglutination reaction with the patient’s serum, and three cells known to be
negative for the antigen that yield a negative reaction with the patient’s serum. Once a clinically
significant alloantibody is identified, blood that is negative for the relevant antigen must be provided. In
such cases, a crossmatch using an antiglobulin reagent (“Coomb’s crossmatch”)--rather than just an
immediate spin crossmatch—is performed prior to the release of red cell units. The time required to
identify one or more antigen-negative units depends primarily on the frequency of that antigen in the
population. (For example, approximately 75% of red cell units are positive for Jka; the blood bank would
have to screen 4 units on average to find one that is Jka-negative.) The chart on the next page lists the
phenotypic frequencies of many clinically important red cell antigens.
You may be called by the blood bank in situations where the floor is requesting blood for a patient
in whom an unexpected antibody has been detected. Your job is to facilitate communication between the
blood bank and the primary physicians regarding the clinical significance of the antibody and how long it
will take to find compatible units of red cells. In rare emergency situations, it may be necessary to give
incompatible units of blood for patients that cannot wait for the completion of an antibody workup.
23
24
2.3 Component usage guidelines
2.3.1 Red Blood Cells
Red blood cell transfusions are indicated to increase the oxygen carrying capacity for patients in
whom the oxygen supply does not meet the oxygen demand of the tissues. There is no single laboratory
test (e.g. hematocrit) that can be used as a red cell transfusion “trigger;” the risks and benefits of red cell
transfusion need to be considered case-by-case. The patient’s age and clinical condition needs to be taken
into account, and the signs and symptoms of anemia (lightheadedness, weakness, pallor, tachycardia,
dyspnea on exertion, etc.) should be searched for. A few general points:
1. RBC transfusion is almost never indicated with a Hgb > 10 g/dl, and is almost always
indicated with a Hgb < 7 g/dl.
2. It is reasonable to transfuse patients with cardiac disease to a Hgb of 10 g/dl. Non-cardiac
patients may do fine with hemoglobin levels of 7-9 g/dl, even in the critical care setting
(NEJM 340;6: 409).
3. Sickle cell anemia patients should never be transfused to a Hct > 30%. The increased blood
viscosity can actually worsen intravascular sickling and clinical symptoms.
4. RBC transfusion can often be avoided in patients with chronic anemia secondary to metabolic
problems. For example, most patients with iron deficiency anemia should almost always be
treated with iron supplementation rather than blood.
5. As a rule of thumb, one unit of packed red blood cells is expected to increase an average-sized
patient’s Hgb by 1 g/dl and hematocrit by 3%.
2.3.2 Platelets
In patients with functional platelets, spontaneous bleeding does not generally occur with platelet
counts above 10,000/l. The BMT service in fact uses a platelet count < 10,000 as their “trigger” for
prophylactic platelet transfusion. Remember that 1 unit of single donor platelets (SDP) is roughly equal
to a pooled 6-pack of random donor platelets (RDP), and should contain at least 3 X 1011 platelets. An
SDP (or a pool of RDPs) should bump the platelet count by 30,000-60,000 unless the patient is
alloimmunized or is consuming platelets secondary to bleeding, sepsis, etc. A number of formulas have
been developed to assess platelet recovery (e.g. the Corrected Count Increment); in practice these
formulas are used in published studies but are not often utilized in everyday practice.
Platelet transfusion guidelines:
Platelet count
Recommendation
< 10,000
Prophylaxis: transfuse 1 SDP or 6-pack of RDP
< 30,00-50,000
Transfuse if pt. is to have an moderately invasive
procedure (e.g. line placement) or in the presence of active bleeding.
Note: platelet transfusions are generally not needed for bone marrow
biopsies/aspirates, even at very low counts.
Comments
Patients undergoing cardiothoracic surgery represent a special case, because often they have been
placed on bypass and their core body temperature is low, resulting in poor platelet function. These
acutely post-op (or intra-op) patients may benefit from platelet transfusion even with a normal platelet
25
count. Another scenario where platelet transfusion in the setting of a normal count may be appropriate is
in bleeding patients who have recently received aspirin or other platelet inhibitors such as Plavix
(Clopidogrel).
PLATELET REFRACTORINESS
Common causes of decreased responsiveness to platelet transfusion
Chemotherapy
Multiple previous platelet transfusions (10+)
Platelet-poor units
Sepsis
ABO incompatible
Fever
Older platetlets
splenomegaly
Amphotericin B
heparin
DIC
Active bleeding
`
Risk factors for platelet refractoriness
Lymphocytotoxic antibodies (PRA+)
Fever
heparin
bleeding
Immune-mediated causes of refractoriness
Anti-HLA antibodies
Anti-platelet antibodies
ITP
Heparin-induced thrombocytopenia
Drug hapten effects (antibiotics, procainamide)
TRAP trial Follow-up study definition of platelet refractoriness:
Post-transfusion platelet count increment 11,000/l
CAP Definition of platelet refractoriness:
CCI < 7500/l from 2 or more sequential transfusions when measured 10-60 minutes after
infusion is complete.
CCI =
[Posttransfusion platelet count – pretransfusion platelet count]
-------------------------------------------------------------------------(No. of platelets transfused x 1011) X (Body surface area)
Body surface area (m2) = 0.20247 x Height(m)0.725 x Weight(kg)0.425
It has been shown that using a raw platelet count increment instead of the CCI to evaluate platelet
transfusion response dramatically increases the incidence of refractoriness (18->27%), indicating that
platelet-poor units and large patients are frequent causes of apparent or pseudo-refractoriness. Therefore,
if refractoriness is being seriously considered for a patient, a true CCI is necessary.
Protocol for management of refractoriness to platelets:
1. When consulted by a primary team about a patient’s poor response to platelet transfusion, ask
about modifying factors as listed above that may influence response to platelets, in particular
history of chemotherapy and number of previous transfusions. Place patient on restrictions for
26
2.
3.
4.
5.
6.
freshest-possible ABO-matched platelets, confirm that they’re already on leukoreduced
restrictions. Ask for post-transfusion counts to determine platelet increments for the next 2
transfusions. If the patient doesn’t meet criteria for refractoriness (11,000/l), but is still
consuming large numbers of platelets, it suggests a non-immune cause of poor responsiveness, and
the clinical team should be counseled accordingly—i.e., “Your patient is not platelet refractory
and therefore does not need HLA-matched or cross-matched platelets.”
If the patient meets the TRAP criteria for refractoriness, ask the team to send a specimen (red top
or red/black top tubes for serum) to tissue typing for the FlowPRA test for anti-HLA (class I)
antibodies. Specify that PRA single antigen specificities should be determined (the tissue typing
lab will be made aware of the protocol we prefer they use so that when the team orders the test
they can advise them as well). Also advise the team that the patient will be placed on HLAmatched platelets temporarily until the FlowPRA results are back. If the patient hasn’t been typed
yet, ask the team to send blood (green top tube) to the tissue typing lab for class I HLA typing.
The tissue typing lab will transmit the HLA type to Dana Farber for HLA matching, and the
results of this match will go to the BWH blood bank. The FlowPRA results will also go to the
Brigham blood bank for Antigen Exclusion Matching. With these results, the BWH blood bank
will first check its stock for category A or BU matches (a match with no incompatible class I
antigens present in the donor). If an A or BU match isn’t available, the technologists will screen
units for antigens of exclusion (Antigen Exclusion Matching).
If the FlowPRA is negative, discontinue HLA unit matching.
If the patient is refractory and has a threatening active bleed or a scheduled procedure, attempt to
find directed donors from any recent transfusions the patient responded well to. If this doesn’t
provide sufficient donors find HLA A or BU matches from our donor lists. If we cannot obtain
donations from any HLA A or BU matches, or there isn’t time for directed donors, order
crossmatched platelets from the American Red Cross.
If there is evidence of clinically significant immune-mediated platelet consumption and all the
above attempts at providing compatible donor platelets have failed, you may wish to consult
hematology regarding alternative interventions such as splenectomy, IVIG, or immunomodulators,
which have shown some clinical value in isolated case reports. Remember that the FlowPRA,
HLA, and platelet crossmatch will each take about a day and aren’t done on weekends, so think
ahead.
References
1. Petz LD, Garratty G, Calhoun L, Clark BD, Terasaki PI, Gresens C, Gornbein JA, Landaw EM,
Smith R, Cecka JM. Selecting donors of platelets for refractory patients on the basis of HLA
antibody specificity. Transfusion. 2000 Dec;40(12):1446-56.
2. Heal JM, Blumberg N. Optimizing platelet transfusion therapy. Blood Rev. 2004 Sep;18(3):14965.
Sacher RA, Kickler TS, Schiffer CA, Sherman LA, Bracey AW, Shulman IA; College of
American Pathologists.Transfusion Medicine Resource Committee. Management of patients
refractory to platelet transfusion. Arch Pathol Lab Med. 2003 Apr;127(4):409-14.
2.3.3 Fresh frozen plasma (FFP)
FFP contains all clotting factors at a concentration of 1 unit/ml. Each unit has a volume of ~250 cc, and is
stored at –18 oC for 12 months.
Indications for FFP transfusion:
1. Therapy for multiple coagulation factor deficiencies as evidenced by prolonged PT and/or
PTT in a patient who is bleeding or at risk of bleeding. Examples include patients with liver
27
disease who are bleeding or at risk of bleeding due to planned invasive procedures, patients
with DIC, or massively transfused patients who may develop dilutional coagulopathy. In
patients with abnormal liver function, it is often impossible to completely correct the PT with
FFP, due to (1) the short half-life of Factor VII and (2) limits on the volume of FFP possible to
infuse into a patient.
2. Therapy for thrombotic thrombocytopenia purpura.
3. Immediate reversal of warfarin effect in situations where there is insufficient time to use
vitamin K. Vitamin K should be used rather than FFP whenever possible. Remember that FFP
has clotting factors at normal plasma concentrations (~1 U/ml), so that it may take 6 or more
units of FFP to reverse a PT prolonged to 16-17 seconds. Vitamin K 5-10 mg p.o. will reverse
coumadin within 24 hours and should not result in a coumadin-resistant state. 25-50 mg p.o.
will result in coumadin resistance for approximately 4-5 days. This should not be of concern in
the immediate postoperative period since heparin is used as an anticoagulant. 50 mg
intravenous vitamin K will normalize the PT within 6 to 12 hours, however, the IV
formulation carries an added risk of allergic reactions.
4. Correction of specific coagulation factor deficiency for which a purified product is
unavailable (fibrinogen, antithrombin III, Factor II, V, VII, X, XI, protein C or S).
Inappropriate Use of FFP
1. FFP should not be used as a volume expander.
1. FFP should not be used to treat bleeding alone, or prolonged PT or PTT alone.
2. Standing orders for FFP are inappropriate.
Comments
FFP is indicated for bleeding patients with a PT or PTT prolonged to 1.5X control values. FFP
may not be of significant benefit in patients with more modest prolongations of the PT/PTT.
Keep in mind that Factor VII has a very short plasma half-life (4-7 hours). For this reason,
when FFP is used to try to acutely correct a prolonged PT in preparation for an invasive a procedure, it
is best to give the FFP just before the procedure
The decision to transfuse FFP will necessarily rely on evidence of coagulopathy as
documented by laboratory evaluation. In emergent situations, where laboratory results may not be
available, samples for these tests should be submitted before FFP is given.
2.3.4 Cryoprecipitated AHF (“Cryo”)
Cryoprecipitate is produced by thawing fresh frozen plasma at 4oC and collecting the insoluble
fraction. (The soluble fraction remaining is “cryo-poor plasma” aka “cryosupernatant”). Each unit (“bag”) of
Cryo has a volume of 10-15 cc. Cryo contains the following: (1) Fibrinogen (150-250 mg/bag) (2) von
Willebrand Factor (80 U/bag) (3) Factor VIII (80-120 U/bag) (4) Factor XIII (40-60 U/bag) (5)
Fibronectin. Cryoprecipitate is not a concentrated form of FFP--it contains insignificant amounts of the other
coagulation factors. Cryo is frequently ordered inappropriately for bleeding patients who actually need
plasma, because the physicians want to correct a coagulopathy while giving less volume. Cryoprecipitate is
indicated in the setting of a bleeding patient who has a fibrinogen level <100 mg/dl (e.g., DIC). Rule of
thumb: in the absence of bleeding, one unit of Cryo is expected to raise an adult patient’s fibrinogen level by
~7 mg/dl. By this estimate, 14 units of Cryo are required to raise a non-bleeding patient’s fibrinogen by 100
mg/dl. Checking the patient’s fibrinogen level is always a good idea in situations where Cryo is requested. In
the absence of data (the usual case) the usual starting dose is 10 units. Bear in mind that a single unit of FFP
actually contains twice as much fibrinogen as a single unit of Cryo; the chief advantage of Cryo is its low
28
volume. Cryo used to be the product of choice for von Willebrand disease (vWD). In recent years, a number
of purified Factor VIII concentrates (e.g. Humate P, Koate) have been determined to contain von Willebrand
Factor, and these are now preferred for the treatment of vWD due to a lower risk of viral transmission.
2.3.5 Clotting factor concentrates
You will be called by the blood bank to approve the release of clotting factor requests, to ensure that
the patient is receiving the appropriate product at the proper dose. Contact the clinicians immediately to
determine the patient’s diagnosis and clinical presentation. The severity of an acute bleed (or the relative
invasiveness of a planned procedure) will determine the target plasma level of the relevant clotting factor; the
appropriate dose should be decided in conjunction with Hematology. (If the patient does not have a
hematology consult, suggest one.) The initial evaluation of these patients (even well-known hemophiliacs)
should include a PTT and a PTT 50:50 mix to screen for the development of a new inhibitor, in addition
to the fVIII or fIX activity level. One of your jobs is to ensure that the blood bank has sufficient amounts of
product on hand to cover the anticipated need, especially over the weekend. You should discuss any clotting
factor dosing and availability issues with both the blood bank supervisors and the blood bank attending on
service. Refer to the Clotting Factor Concentrates table below for dosing information on the various factor
preparations.
a) Factor VIII dosing
In the absence of an inhibitor (see below), fVIII levels will increase 2% for every 1 unit/kg
infused. Assuming a starting plasma level of 0%, a 100% fVIII level can be achieved by giving
a 50 U/kg IV bolus. This is ordinarily followed by doses of 25 U/kg q12 hours. Dose
adjustments are made based on trough levels in patients with moderate-severe bleeds.
b) Factor IX dosing
Factor IX has somewhat different pharmacokinetic properties than fVIII. A 100% fIX level can
be achieved by dosing at 100 U/kg, followed by 50 U/kg q24 hours.
c) Patients with inhibitors
A few products are available for the particularly challenging situation of a patient who has
developed a coagulation factor inhibitor. These are generally IgG antibodies, which neutralize
the activity of a factor. Inhibitors to a variety of factors are seen clinically, but the classic
scenario is the severe hemophilia A patient who develops a fVIII inhibitor after being exposed
to fVIII concentrate. The therapy will depend on the clinical situation (bleeding or not,
coverage for a procedure, etc) as well as the antibody titer. Inhibitors are quantified using
Bethesda Units (BU), defined as the inverse of the inhibitor titer able to neutralize 50% of
normal factor activity in a 50-50 mix with pooled plasma. Low-titer inhibitors to fVIII (<5-10
BU) can often be “swamped” by giving excess factor VIII. When the titer rises above ~10 BU,
it may be necessary to give one of the following preparations:
Porcine Factor VIII (Hyate:C), purified from pooled porcine plasma, can substitute for
human fVIII in the coagulation cascade. Often there is little or no cross-reactivity between an
inhibitor to human fVIII and porcine fVIII. A Bethesda titer for porcine fVIII should be
obtained if you are contemplating using this product. Porcine fVIII should be reserved for
serious bleeding episodes/invasive procedures in patients with high-titer inhibitors, since it is
common for patients to make antibodies specific for porcine fVIII upon exposure.
Prothrombin complex concentrates, also called “Factor IX complex concentrates,”
are another therapeutic option in this setting. Currently, the blood bank carries FEIBA, which
contains non-activated factors II, IX and X, and activated fVII. Autoplex, and occasionally the
29
intermediate purity fIX concentrate Konyne are also used locally. Dosing is empiric. These
products are risky to give (thrombogenic), but may be life-saving in dire emergencies.
Recombinant Factor VIIa (NovoSeven) has recently been approved by the FDA, and is
probably the agent of choice for bleeding in the setting of a high-titer inhibitor. The dose for a
patient with an inhibitor is 90 mcg/kg; doses are repeated q2-3 hours as needed. If NovoSeven
is required for off-label use (i.e. bleeding outside the setting of a hemophiliac with an inhibitor)
both a Hematology attending and a Blood Bank attending need to be involved in the decisionmaking process. Refer to rFVIIa guidelines below:
JPTM GUIDELINES FOR
rFVIIa
Dose* Frequency
Situation
FVIII or FIX inhibitor, with active
q 2 hours until hemostasis
bleeding or undergoing a surgical 90 mcg/kg
achieved.
procedure
Congenital FVII deficiency, FVII
activity < 25%, with active
q 2 hours until hemostasis
20mcg/kg
bleeding or undergoing a major
achieved.
surgical procedure
Comments
Dose/frequency titered as
necessary with Hematology
consultation.
As a supplement to FFP infusion.
Also give vitamin K 10 mg IV over
20 minutes. If pt. can tolerate
volume, give FFP 15-20 cc/kg to
replace other vitamin K
dependent factors.
As a supplement to FFP; monitor
If bleeding does not decrease in
coagulation parameters, transfuse
nd
40 mcg/kg 30-60 minutes, consider 2 dose
with blood components as
or surgical reexploration.
needed.
Urgent warfarin reversal:
(prolonged INR with life40 mcg/kg 1 dose.
threatening bleed e.g. intracranial
hemorrhage)
Uncontrolled bleeding
associated with trauma, surgery
and liver failure, no identifiable
surgical source
Intracranial hemorrhage (off
40 mcg/kg 1 dose.
warfarin)
rFVIIa should be given within 4
hours of bleed.
* Dose will be rounded to the
closest 1.2 mg vial

rFVIIa should be used with caution in patients at risk for thrombosis (e.g. CAD, h/o
thrombosis, ECMO/VAD, DIC).

All off-label use of rFVIIa must be approved by the Transfusion Medicine attending on-call.

Hematology consultation is recommended for all patients receiving rFVIIa.
d) Humate P dosing in von Willebrand Disease
At this time, Humate P is the only Factor VIII concentrate officially licensed by he FDA
for the treatment of vWD. Note: Humate P vials are actually labeled with both von
Willebrand Factor units and Factor VIII units (~ 3:1 vWF: fVIII; exact levels vary by lot).
Ordering physicians may not be aware that the Blood Bank always dispenses Humate P
based on von Willebrand units.
30
2.3.6 Granulocytes
Granulocyte transfusions are used only rarely. They may be indicated for patients meeting all
of the following criteria:
1. bacterial or fungal sepsis
2. infection not responding to appropriate antibiotics
3. absolute neutrophil count less that 500/mm3
4. marrow aplasia with probability of recovery within a few weeks.
(Exception: Cases of documented neutrophil dysfunction do not need to have neutropenia.)
If granulocyte transfusions are approved, donors can be arranged through the Kraft Donor
Center. Granulocytes do not express ABO antigens, however the products are always
contaminated with fairly high numbers of RBCs (~30-50 cc), and so it is mandatory to use
donors whose RBCs are ABO-compatible with the recipient’s serum. Additionally, it may be
advisable to check an HLA antibody screen (PRA) on the recipient. If the recipient has made
high-titer anti-HLA antibodies, giving granulocytes from HLA-matched donors may help avoid
TRALI-like reactions.
Granulocyte donors need to meet all the same criteria as volunteer platelet donors in order to
donate. Intravenous hydroxyethyl starch (Hetastarch), a colloid solution, is used during
granulocytapheresis as a red cell-sedimenting agent. This substance is cleared extremely
slowly from donors (over months), causes plasma volume expansion (sometimes headaches)
and has been rarely associated with severe allergic reactions. For these reasons, people with a
history of migraine headaches or allergies to corn should ordinarily not serve as granulocyte
donors.
Granulocyte products are required by the FDA to be transfused within 24 hours of
collection. They are therefore designated as “emergency release” by the blood bank, and issued
prior to the completion of the standard pretransfusion viral testing. Granulocyte products should
be irradiated, but obviously not filtered.
It is the responsibility of the Blood Bank resident to maintain daily contact with the floor to
ensure that a granulocyte product is needed for each day. A lot of time and effort goes into
collecting these products, and it is desirable to avoid the situation where a granulocyte donor is
put on the machine while the floor has already decided to discontinue therapy. Additionally, in
the case of fungal infection, the floor team must be notified to schedule amphotericin 12 hours
before or after granulocyte infusion to prevent accelerated destruction of the infused cells.
Generally only CMV negative transplant patients need CMV negative products. Since the
use of granulocytes is in the setting of life-threatening infection, the need for the products often
outweighs CMV concerns.
Neonatal cases do not need to wait for documentation of infection and should receive split
granulocyte products every 12 hours for 2 days. Average concentrations of these split products are
9
10 granulocytes /15 ml and the usual dose is 15 ml/kg. Orders for different schedules can be
honored. Emergency neonatal needs which cannot wait for a pheresis product may be handled
with buffy coats arranged through the ARC physician on call.
Granulocytes therapy should be discontinued or the schedule should be decreased when:
1. the granulocyte count normalizes, or
31
2. cultures are negative and there is no clinical evidence of infection for 72 hours.
This is an expensive and difficult-to-obtain product. If the product will not be needed,
cancel ASAP.
2.3.7 SOPs for the administration of Blood Products
BWH
www.bwhpikenotes.org
Patient care services --> Nursing --> Clinical Practice Manual --> Blood
Policies
Children's
Children's internal home page -> Clinicial Site tab -> Nursing ->
Nursing Policy and Procedure Manual -> Chapter 3, Fluid Management ->
3.2 Blood Products
Website:
http://elibrary/main/Documents/Patient%20Services/02%20Manuals,%20Polici
es%20and%20Standards/Nursing%20Patient%20Care%20Policy%20and%20Procedure
/03%20Fluid%20Management/03.2%20Blood%20Products/
32
2.4 Transfusion reactions
For any reported reaction to transfusion of a blood product the following steps should be taken by the
floor:
1. The transfusion should be discontinued if suspicious signs/symptoms are noted (e.g. fever,
chills, unexplained hypotension: see refs more complete discussion) and IV lines kept open
for potential fluid resuscitation.
2. The following samples/items should be sent to the blood bank ASAP:
a. completed, signed transfusion reaction form ( normally attached to the product in
question)
b. the product/bag itself which is suspected to have caused the reaction ( and any bag
transfused before reaction in reasonable time frame. e.g. if two units of RBCs transfused
and reaction is noted during the second, send both if available)
c. one clotted (red top) and one anticoagulated (purple top) post transfusion blood
specimen, each properly labeled and accompanied by a Blood Bank requisition form
3. A freshly voided post transfusion reaction urine sample should be sent to chemistry for
urinalysis to evaluate for hemoglobinuria.
4. Blood cultures on the recipient should be sent if a septic transfusion reaction is suspected (e.g.
hypotension, high fever).
The following steps will be taken by the technologist in the blood bank:
1. Clerical check (check of all paperwork, computer, log book against product label,
requisition form)
2. Visual examination of pre and post serum/plasma for hemolysis and icterus
3. Direct Antiglobulin Test on post transfusion specimen
 If the DAT is positive on the post-transfusion specimen, additional testing is done,
including:
o ABO/Rh/Ab screen/repeat crossmatch
o If the DAT is positive using anti-IgG: an eluate/antibody ID is performed
4. Culture of remaining product, if the recipient had evidence of infection e.g. fever
Be aware that the blood bank will not release further blood products to any patient following a
transfusion reaction without the approval of a blood bank physician. If the floor asks to transfuse a
patient after a reaction has been called, the blood bank will page you. Determine the following:
1) What product was transfused? What product is now being requested?
2) What was the nature of the transfusion reaction? (Change in vital signs?)
3) What are the results of the transfusion reaction work-up? (is there laboratory evidence for
hemolysis e.g. positive DAT?)
4) Has the patient had any previous transfusion reactions/does the patient have any anti-RBC
antibodies?
Inform the blood bank whether it is acceptable to release more blood products based on the reaction history
and workup. Let them know if you recommend any additional maneuvers: (e.g. premedication with Benadryl
to prevent allergic reactions, etc.) A table of the most clinically important transfusion reactions is presented on
the next page.
33
TRANSFUSION REACTIONS
Reaction Type
Acute Hemolytic
Transfusion
Reaction
Mechanism
Pre-formed red cell
antibody
Delayed Hemolytic
Transfusion Reaction
Primary or amnestic
red cell antibody
response ~1-2 weeks
post-transfusion
Antibody v. donor
WBCs or
Cytokine-mediated
Febrile Nonhemolytic
Transfusion Reaction
Signs/Symptoms
fever, hypotension,
flank pain, chest pain,
nausea/vomiting, chills,
shock, renal failure,
DIC
Usually asymptomatic
Rarely, clinical picture
similar to acute
hemolytic txn rxn.
Fever > 1oC
Chills/rigors
Lab Diagnosis
clerical error?
DAT positive
hemoglobinemia,
hemoglobinuria
Treatment
Stop transfusion;
Maintain IV access;
Hydrate w/ NS +/diuretics.
Hgb/Hct
bilirubin
DAT positive
(usually)
Blood bank
hemolytic workup
negative; culture
of unit negative
Monitor CBC, renal
status.
Transfusion of
bacterially
contaminated
product
Allergic Reaction
Product seeded by
donor skin flora, or
donor bacteremic;
growth during storage
Allergy to donor
plasma protein
Fever, shock,
hemoglobinuria
renal failure, DIC
Culture of product
and patient
Hives, itching
Occ. wheezing, BP
N/A
Anaphylactic
Reaction
Antibody to IgA
Hypotension/shock
IgA levels
Anti-IgA Ab
Congestive heart
failure
Volume overload,
usually in pts. w/
heart dz getting PRBCs
Ab to recipient WBCs
(usually anti-HLA)
ARDS
Signs of congestive
heart failure
Donor lymphocytes
versus host; rarely
seen in immunocompetent pts who
share HLA w/ donor
Charged filters/artificial surfaces
activate bradykinins; pts. on ACE
inhibitors can’t clear them.
Ab-mediated platelet
destruction; usually
in multiparous
women who are PlA1
negative.
Fever, rash, diarrhea,
severe pancytopenia
pO2
pulmonary edema
on CXR
pO2; pulm
edema on CXR;
Work up donor for
anti-HLA Abs.
CBC, LFTs
skin biopsy
Hypotension
N/A
Severe pancytopenia
~ 1 week after
transfusion.
CBC, PlA typing
Transfusion Related
Acute Lung Injury
(TRALI)
Transfusion-related
Graft-Versus-HostDisease (GVHD)
Hypotensive reaction
Post-Transfusion
Purpura (PTP)
Acute respiratory
distress, usually
within 6 hours of txn.
Stop transfusion; R/O
acute hemolytic rxn or
bacterial contamination.
Premedicate w/ Tylenol;
Use leukopoor products.
Broad-spectrum
antibiotics, fluids,
pressors
If urticaria only sign,
may re-start transfusion.
Premedicate w/
Benadryl 25-50 mg iv.
Epinephrine, fluid
resuscitation, intubation;
Prevent w/ washed blood
products.
Transfuse slowly;
Diuretics.
Supportive care; usually
resolves within 96 hrs
Supportive care;
immunosuppression;
Prevent w/ irradiated
blood products.
Mortality rate is high.
BP support; D/C
ACE inhibitor
Plasma exchange or
IVIG
34
35
36
2.5 RhIg administration
Because of inventory limitations, RhD-negative recipients may sometimes be issued RhD-positive
platelet units. (This is never done for RhD-negative women of childbearing age.) Notify the house officer
taking care of the patient that that because platelet units contain a small volume of RBCs, the patient may
become sensitized to the RhD antigen. To try to prevent sensitization, our policy is to recommend
administering Rh Immune globulin (RhIg). The RhIg dose in this situation is 1 vial (300mcg). The route
varies by brand: Rhogam is only given IM; WinRho is only given IV; Rhophylac is given either IM OR IV.
RhIg is ordered on the floor and sent up by the blood bank. The rationale for trying to prevent RhD
sensitization in patients who are not women of childbearing age is that the presence of anti-D in the serum
might slow down a future blood bank serologic workup in a situation where the patient may need blood
emergently. Note that the BMT service has a policy of giving RhIg to all Rh- patients who receive Rh+ blood
products.
Occasionally you will be asked to help dose RhIg in the setting of an Rh(D) negative woman with a
fetal-maternal bleed. One vial of RhIg contains 300 g RhD and is sufficient to suppress the immune
response to 15 ml Rh positive packed red cells or 30 ml whole blood. The Kleihauer-Betke (K-B) test
can be used to quantitate the amount of a fetal-maternal bleed. This test is based on the fact that in the
presence of acid, fetal red cells will maintain normal staining characteristics whereas adult red cells will
appear as “ghosts.” The number of fetal red cells present in the sample is determined by manual counting
and is expressed as a percentage of the total red cells.
To calculate the number of vials of Rhogam required, the following rule-of-thumb is used:
# vials RhIg required = 50 X %fetal red cells  round-off +1 vial
30 ml/vial
The “50” assumes that all women have a 5 liter blood volume. The percent fetal red cells is provided by
the K-B test result. One vial of RhIg covers a 30 ml bleed, and 1 extra vial is provided “for good
measure.”
37
3. BWH BLOOD DONOR CENTER/APHERESIS UNIT
3.1 Therapeutic apheresis
During apheresis, blood is centrifuged and separated into components by density. Depending on
the procedure, platelets, red cells, white cells or plasma is collected, and the remaining components are
returned to the patient. Photopheresis is a special category of apheresis procedures, where the buffy coat
is collected from a patient, the collected white cells are inactivated with psoralen and UV irradiation, and
then returned to the patient.
3.1.1 Indications
Apheresis has been attempted as a therapy for a large number of diseases. Both the American
Association of Blood Banks (AABB) and the American Society for Apheresis (ASFA) have published
guidelines reflecting the current thinking regarding the efficacy of apheresis for various clinical entities.
Diseases are assigned to one of four categories based on available studies in the literature (AABB Technical
Manual 13th ed. pp. 136-7):
Category I: standard acceptable therapy
Category II: sufficient evidence to suggest efficacy usually as adjunctive therapy
Category III: inconclusive evidence of efficacy or uncertain risk/benefit ratio
Category IV: lack of efficacy in controlled trials
Indications for emergency therapeutic pheresis include:
TTP: This is a potentially fatal disease that can have a rapidly progressive course, so plasma exchange
should be initiated as soon as possible. Follow the platelet count, Hgb/Hct, LDH, and creatinine daily. (The
presence of schistocytes on the peripheral smear is critical for the initial diagnosis of TTP, but other
parameters, particularly the platelet count, are more useful for monitoring the patient.) In contrast to most
conditions, plasma is always used as the replacement fluid for TTP. Our standard therapeutic approach for a
newly-diagnosed patient with TTP is to perform daily plasma exchanges until the platelet count stays in the
normal range for ~3 days, then stop and observe the patient’s counts. Cryosupernatant (“cryo-poor FFP”) is
used for replacement in patients who fail to respond after ~5 plasma exchanges.
Myasthenia Gravis: Common indications for plasma exchange include:
(1) shortness of breath (risk of respiratory failure) (2) difficulty swallowing (risk of aspiration) and (3)
preparation for thymectomy. Plasma exchange is frequently used to try to prevent a patient from requiring
intubation, or to hasten a patient’s removal from the ventilator. Key respiratory parameters to follow are
negative inspiratory force (NIF) and forced vital capacity (FVC). Patients are typically pheresed ~every other
day for 5 days, using 5% albumin in normal saline (NS) as a replacement fluid. Because coagulation factor
levels are lowered when using albumin replacement, the PT/PTT should be monitored. If the PT prolongs
more than a few seconds, or if any other additional bleeding risk is present, FFP should be considered. (A
typical maneuver is to use 5% albumin/NS for the beginning of the procedure, and then to use FFP for the last
liter of replacement.)
Sickle Cell Disease: The efficacy of red cell exchange has been best established for: (1) evolving
stroke (2) sickle chest syndrome and (3) refractory priapism. Hematocrit and
%Hgb S goals (usually Hct = 30%; Hgb S = 30%) are decided in conjunction with Hematology. In most
cases, the patient is assumed to have a starting Hgb S of 100%. Generally, these patients are not transfused to
hematocrits above 30%, as higher hematocrits can impair blood flow and actually worsen the clinical
condition. The replacement product of choice is prestorage leukoreduced PRBCs (theoretically less likely to
cause transfusion reactions). These patients should be premedicated with Benadryl (25 mg IVP) and Tylenol
38
(650 mg po) prior to the procedure to reduce the chance/severity of an allergic reaction, and to try to prevent
having to halt the procedure because of a febrile reaction. (Hemolytic transfusion reactions can present with
fever.) Order a post-procedure CBC and Hgb analysis.
Guillain-Barré: As with myasthenia gravis, the primary indication for plasma exchange is to prevent
patients from having to be intubated, or to shorten their course on the ventilator. Patients who are in imminent
danger of respiratory failure are treated on an emergent basis.
Leukoreduction: Patients with acute leukemia may present with symptoms of hyperviscosity
secondary to leukostasis in the cerebral or pulmonary vascular beds. Usually this is seen in patients with
extremely high blast counts (> 100,000/l.) Leukapheresis may be requested to acutely lower the white count
prior to the initiation of chemotherapy.
Goodpasture’s Disease: Acute removal of the pathologic anti-basement membrane antibody is done to
preserve lung and kidney function. In patients with hemoptysis, FFP is a good choice for replacement.
Posttransfusion purpura (PTP): This is a rare antibody-mediated thrombocytopenia typically seen in
multiparous women ~1 week after receiving a blood product. Thrombocytopenia can be very severe
(<10K/l). Daily plasma exchange is performed until the platelet count recovers (usually prompt). IVIG is
also an effective treatment for this disorder, and is often used as the first-line therapy.
Heart and kidney transplant rejection: Plasma exchange is occasionally instituted in this setting,
particularly in pediatric patients.
3.1.2 Venous access
A line to draw blood from, and a line to return blood are needed to perform an apheresis
procedure. Either peripheral IVs or a double lumen central venous catheter may be used. For
patients who are relatively stable, peripheral access is preferred as it avoids the risks associated
with central lines. These risks include bleeding, pneumothorax, and bacterial infection, often seen
when lines are left in for more than a few days. Nevertheless, central lines are often unavoidable,
particularly in elderly/very sick patients (dehydrated, poor veins, etc). In a middle-of-the-night
emergency (e.g. a new case of TTP), a femoral line is often a good choice. These can be put in at
the bedside, and there is no risk of pneumothorax. A chest line can be put in later for anticipated
longer-term therapy. Dialysis-compatible catheters (e.g. Quintens, Vascaths) are the central line
types of choice, since they are large and rigid enough not to collapse under the pressures generated
by the fairly high flow rates (50-100 cc/min) generated during apheresis.
3.1.3 Adverse reactions to apheresis
Apheresis is generally very well tolerated, and serious adverse reactions are fortunately rare. The
biggest risks of apheresis actually relate to the use of central venous catheters (see above). Improper
placement of a central line can result in hemorrhage and death, so it is critically important to have radiographic
documentation of correct placement before proceeding with apheresis therapy.
The most common adverse reactions observed during apheresis procedure are caused by the calciumchelating citrate anticoagulant. Citrate toxicity can be particularly problematic in patients with hepatic
disease, as they may clear the citrate at a slower rate. The most common citrate reactions take the form of
paresthesias around the mouth or in the fingertips. Some patients report vibratory sensations. More severe
reactions due to lower calcium levels can lead to nausea and vomiting, cramping/tetany, hypotension, and in
the most severe cases, seizure or cardiac arrhythmias. Mild citrate reactions can almost always be managed by
slowing or stopping the apheresis procedure and/or administering po calcium (TUMS). In more severe cases,
it may necessary to administer calcium intravenously. A safe approach is to give a 1 gm bolus of calcium
39
gluconate IV over 15-20 minutes; this can be repeated until the ionized calcium level reaches the normal range
(1.13-1.32). Additional IV calcium may be given as a drip over the remainder of a procedure.
Vasovagal reactions (see section 3.2.3, below) may be seen with any apheresis procedure. These are
often seen in plasma exchange procedures for neurologic patients. These patients often require extra boluses
of 5% albumin/saline to maintain their blood pressure for the procedures. When peripheral venous access is
used, there is always the possibility for adverse reactions to venipuncture (hematoma; rarely, peripheral nerve
injury). Finally, any time blood products are used as the replacement fluid (e.g. red cell exchange)
transfusion reactions are a possibility (see section 2.4).
40
3.2 Whole blood donation
Recommended reading: Technical Manual 13th ed., pp. 89-128; Donor room SOPs.
3.2.1 Allogeneic donors
There are four categories of allogeneic donors:
(1) Volunteer donors are community donors donating either on-site or at a mobile blood drive.
The eligibility criteria for volunteer whole blood donation are detailed in Chapter 4 of the
Technical Manual and in the donor room SOP manual. Essentially, these are healthy
individuals. Allogeneic donors can donate whole blood once every 8 weeks.
(2) Directed donors are donors requested by the patient to donate for him or her. These
donors must meet the same eligibility criteria as volunteer donors in order to donate. These
products may be crossed over to the general pool if they are not used for the designated
recipient.
(3) Medically directed donors are donors selected by a physician for a particular patient. An
example would be HLA-matched platelet donors. These donors must meet the same criteria
as volunteer donors in order to donate. These products may be crossed over to the general
pool if they are not used for the designated recipient
(4) Medically restricted donors are donors chosen by a physician for a particular patient,
where the medical circumstances necessitate using a specific donor who does not have meet
the usual eligibility requirements for volunteer donation. These units may not be crossed
over into the general pool.
3.2.2 Autologous donors
These are donors donating for themselves in preparation for surgery. Blood donated autologously may
not be transfused to any other recipient (no crossover). In general, the eligibility criteria for autologous
donation are much looser than for volunteer donation. For example, the minimum acceptable
hemoglobin level is 11.0 g/dl vs. 12.5 g/dl as used for allogeneic donors. Unlike allogeneic donors, it
is permissible for auto donors with a history of e.g. cardiac disease to donate, provided the donor is
relatively stable. Also, auto donors can donate much more often than every 56 days as for allogeneic
donors. For donors where there are concerns about hemodynamic stability, whole blood donation with
isovolemic saline replacement may be performed. Although blood donation is generally well-tolerated,
there are situations where it is necessary to defer an autologous donor, including:
1.
2.
3.
4.
5.
6.
Evidence of infection/risk of bacteremia
Aortic stenosis/IHSS
Unstable angina
Active seizure disorder
MI or CVA in past 6 months
Patients with significant cardiac or pulmonary disease not yet cleared for surgery by
their primary physician
7. High-grade left main coronary artery disease
8. Cyanotic heart disease
9. Uncontrolled hypertension
Technical Manual, 13th edition, p. 113.
If you are asked by the donor center to evaluate whether a donor is suitable to donate a product,
first be sure to know whether the donor is an allogeneic or autologous donor, as the eligibility
criteria are very different. The essential question to consider is whether a potential donor’s blood
donation will incur an unacceptable risk either to the donor or to the eventual recipient. The
nurses have a detailed checklist of questions for donors, and a list of criteria that will prevent a
41
donor from donating. Your job is to answer the questions that are not specifically laid out in the
protocols. It is hard to predict what types of questions you will get, because anything common is
usually already on the list, but the most common questions that arise tend to fall into these
categories:
1. Active infections. Donors (allo or auto) at risk for seeding their product with bacteria need to be
deferred. Growth of bacteria during storage in platelet units or RBC units has resulted in fatalities.
2. Medications. Most medications taken by donors are not inherently dangerous to the recipients.
Only trace amounts of a drug are likely to be present in a donated unit, and these will be diluted
into the recipient’s plasma volume. In evaluating whether a donor on a particular medication can
donate, the primary consideration is why the donor is taking the medication in the first place. For
example, antibiotic use could indicate a recent or current infection, which would be a cause for
deferral. Alternatively, a donor taking seizure medications may require further questioning before
donation can be approved. Currently, there are only eight drugs for which a deferral is mandated by
the FDA/AABB based on risk to the recipient. They are:
1.
2.
3.
4.
5.
6.
7.
8.
Accutane (isotretinoin; defer from donation at least 1 month from receipt of dose)
Proscar/Propecia (finasteride; 1 month deferral)
Avodart (dutasteride, 6 months)
Soriatane (acitretin; 3 year deferral)
Tegison (etretinate; permanent deferral)
Growth hormone from Human Pituitary Glands (not used after 1985)
Bovine insulin
Hepatitis B Immune Globulin (HBIG given for prophylaxis following an exposure)
You may be asked to talk to a donor and explain to him or why he has been deferred. Be
diplomatic. For people donating for family members (or themselves), it is a good idea to emphasize the
overall safety of the blood supply, and the extremely low (albeit nonzero) risk of viral infection from
transfusion. Explain to repeat donors why they have been deferred, and encourage them to return again
once the cause for deferral has passed.
.
3.2.3 Adverse reactions
On rare occasions you may be paged by the donor center because a donor has become ill. The most common
scenario is a vasovagal reaction. Get the donor’s vital signs over the phone and then go see the donor right
away. The key sign in the diagnosis of a vasovagal reaction is an inappropriately low heart rate in the setting
of acute hypotension. The pheresis nurses are very experienced at dealing with vasovagal reactions, and by
the time you have arrived they will have put the donor’s head down/feet up, administered smelling salts, cold
compresses, etc. Generally, you will not be called unless the donor’s blood pressure has not responded to
these maneuvers. Take a directed history from the donor and do a physical exam as needed. If you diagnose a
vasovagal reaction, it may be appropriate to give a small intravenous fluid bolus. A 250 cc normal saline
bolus is generally a safe way to start; be cautious when giving IV fluids to older/smaller patients who may
have underlying cardiovascular disease.
42
4. DFCI KRAFT FAMILY BLOOD DONOR CENTER
Volunteer platelet donations and peripheral blood stem cell collections performed in Kraft Family
Blood Donor Center is the major source of supply for patients who require platelet transfusion or stem
cell transplantations at BWH and DFCI.
4.1 Apheresis platelet donation
4.1.1 Donor Selection
Plateletpheresis donors may donate every 2 weeks, provided they meet all the same criteria as
whole blood donors. The interval between donations should be at least 2 days and donors should
not undergo plateletpheresis more than twice in a week or more than 24 times in a year. If the
donor donates a unit of Whole Blood or if the donor lost more blood than expected during
plateletpheresis procedure, at least 8 weeks should elapse before a subsequent platelet collection,
unless the extracorporeal red cell volume is less than 100ml. Donation may be permitted for
donors who failed to meet the above requirements if the component is expected to be of particular
value to a specific intended recipient (eg, an HLA-matched donor), provided physician
approval.Donors who have taken aspirin-containing medications within 36 hours of donation are
usually deferred. A platelet count is not required before the first apheresis collection or if 4 weeks
or more have elapsed since the last procedure. If the donation interval is less than 4 wees, the
donor’s platelet count should be above 150,000/l before subsequent plateletpheresis occurs.
4.1.2 Collection Procedure
In plateletpheresis, 5 liters of the donor’s blood is processed through the apheresis machine, and a
single donor platelet unit (SDP) is collected in ~300 cc of plasma. The FDA spcifies that the total
volume of plasma collected should be no more than 500ml (or 600ml for donors weighing more
than 175 pounds). These procedures take ~2 hours; complications are rare. SDP units containing
at least 6.5 X 1011 platelets may be split by the blood bank into two platelet doses.
4.1.3 Donation Complications
Vasovagal and hypovolemic reactions are rare in apheresis donors. Because the plateletpheresis
donors are anticoagulated with citrate during the collection procedure, paresthesias and other
citrate related toxicities are commonly seen.
4.2 Peripheral blood stem cell collection
4.2.1 Rationale
In recent years, peripheral blood stem cells (PBSCs) have been used more frequently for
hematopoietic stem cell transplantation. Harvesting stem cells directly from bone marrow is now a
rarity at many centers. Patients transplanted with PBSCs have been shown to engraft faster than
patients receiving bone marrow transplants. Moreover, PBSC collections are better tolerated by
donors (no general anesthesia/marrow harvest in the OR). PBSC products contain higher numbers
of T cells relative to marrow products; it is controversial as to whether this translates into higher
rates of graft-versus host disease in recipients of unmanipulated products.
4.2.2 Donor Selection and Preparation
PBSC harvests are performed on both autologous (usually patients with hematologic
malignancies) and allogeneic donors. Allogeneic donors receive G-CSF injections for four
consecutive days as their mobilization regimen; on day five of G-CSF injection, PBSC collection
begins. The autologous donors are typically mobilized with both chemotherapy and G-CSF.
Collection of sufficient stem cell numbers for a transplant is easier with the allogeneic donors
because they are healthy individuals donating for a sibling, and their marrow tend not to be
exposed to toxic chemotherapeutic agents previously. To increase the efficiency of PBSC
collection and identify autologous PBSC donors who are difficult to be mobilized due to their
43
disease status or previous chemotherapy /radiation exposure, peripheral blood (PB) CD34 counts
are routinely performed on autologous donor prior to their day 1 of collection. Donors with low
PBCD34 counts are often deferred for collection until their counts are high enough to predict
reasonable yield of CD34+ cells in the collected product. For updated JPTM guideline and
algorithm for autologous PBSC collection using PBCD34 count, please refer to the document
located in Clinical Pathology shared drive (R:\CLINPATH\stem cell lab\PB CD34 collection
algorithm.pdf).
4.2.3 Collection Procedure
In a typical stem cell collection, a large volume of blood is processed through the machine. DFCI
donor room routinely process 3 total blood volumes per collection(unless specified by clinical
protocol) for each donor, which translates to 15 or more liters processed. Unlike most apheresis
procedures, where the patient is left isovolemic, following a stem cell collections the donor
typically is typically left ~1500 cc fluid-positive. A minimal collection target for either an
autologous or allogeneic PBSC donor is 2 X 106 CD34+ cells/kg recipient body weight.
Transplantation of at least 2 X 106 CD34+ cells per patient weight is known to provide a minimum
dose of stem cells to ensure a reasonable time frame (~11-14 days) of neutrophil and platelet
engraftment after transplantation.
4.2.4 Donation Complications
The most frequent complications associated with PBSC collection are from the growth factor
injections. G-CSF typically causes bone pain, as well as flu-like symptoms such as headache and
low-grade fevers. The bone pain is the usually the most troublesome side effect for donors, and
they will often need narcotics for the short period while they are being mobilized. Clinical studies
has shown that G-CSF can transiently induce spleen enlargement and cases of spleen rupture after
the use of G-CSF in context of trauma have been reported. As with therapeutic apheresis, citrate
toxicity is a common adverse event. Because a central lines were often placed to facilitate
multiple days of collection, line infections can be seen fairly often in the immunocompromised
autologous PBSC donor population. If an autologous PBSC donor comes in febrile/ill-appearing,
it is wise to have a low threshold for contacting the primary transplant team.
44
5. CHILDREN’S HOSPITAL BOSTON
5.1 Product Indications and Dosages
Some of the indications and dosages differ in the pediatric population. RBC units, FFP, and
platelet pheresis can be aliquoted. Examples:
 Red Blood Cells;
o Patients with Thalassemia requiring chronic transfusions are usually transfused to
12-15 g/dl to suppress endogenous hematopoiesis.
o RBCs are usually given at a dose of 5-10 ml/kg at a rate of 5 ml/kg/hr.
 Granulocytes; These may be indicated for a patient with chronic granulomatous disease
with an infection.
5.2 Consults
Consults for transfusion reactions, serologic issues, and other non-apheresis issues are entered
directly into the Cerner computer system. Instructions are posted on the wall in Children’s Hospital
Boston blood bank and are detailed below on the next page.
Most of the consults are performed for new antibodies or transfusion reactions. Also, write a
consult for a Rh negative patient who received Rh positive platelets and for whom you are recommending
WinRho. Other miscellaneous issues may cause you to write a consult. An example would be a Bone
Marrow Transplant patient for whom you are changing the blood type of the products that they receive.
Sample consults follow the Cerner Instructions Page.
45
Sample Transfusion Reaction Consult
ABO/RH : A Positive
PRODUCT : Irradiated and pre-storage leukoreduced single donor
platelets (A Positive)
UNIT NUMBER : 30GP11940
Temp BP HR
Pre trans : 37.2 105/67 98
Post trans : 39.3 100/70 95
DAT
hemolyzed
Weak Positive
NO
Weak Positive
NO
Clerical check : OK
Antibody screen : Negative on both the pre- and post-transfusion
specimens
Eluate : Not indicated
Gram stain: Negative
Culture : pending
John Doe 6 year old boy with ALL. On 2/18/04 around
12:25 pm, the patient was receiving 1 unit of irradiated single donor
platelets. After 100 mL were transfused, he developed chills. His
symptoms resolved spontaneously shortly after onset.
Blood Bank evaluation revealed no clerical error and no signs of
hemolysis. DAT was weakly positive on both the pre- and posttransfusion specimens with the same strength of reactivity. The
group/type of both the pre- and post-transfusion specimens are A
positive. Antibody screens were negative on both specimens.
In summary, no evidence of serological transfusion eaction was
identified. The Gram stain is negative and cultures are in progress but
negative to date.
These findings are most consistent with a febrile nonhemolytic
transfusion reaction. The patient has received multiple transfusions
in the past and this is the patient’s first documented febrile
transfusion reaction at CHB. Febrile transfusion reactions are due to
cytokines released by leukocytes in blood components.
At this point, no change in transfusion practice is recommended.
Jane Doe, MD, resident or fellow
46
Sample Serologic Consult
ABO/Rh: A positive
Antibody Screen: positive
Antibody Identified: Anti-K
Red Cell Phenotype: Kell negative
Direct Antiglobulin Test (DAT): IgG weak positive, C3 negative
This patient is a 4 year-old girl admitted for sickle cell crisis. On admission (9/25/99), a routine type and
screen revealed blood type A+ with a negative antibody screen. The patient was transfused with two units
of red blood cells and was subsequently found to have a positive antibody screen. Anti-K alloantibodies
were identified in the patient's serum. These antibodies are directed toward antigens in the Kell blood
group system. These antibodies are considered clinically significant because they can cause hemolytic
transfusion reactions and/or hemolytic disease of the newborn.
As per protocol, the blood bank typed the transfused units and found one of the two
units to be K antigen positive. Retesting of the patient’s original sample from
admission demonstrated weak presence of an anti-K alloantibody. In addition, that
sample had a micropositive DAT for IgG.
The patient's post-transfusion DAT is weakly positive for anti-IgG, slightly increased from previously.
This indicates that IgG antibodies, but not complement, are coating the patient's RBCs. This may or may
not result in shortened RBC survival. Eluate studies were performed to try to identify the specificity of
the antibody coating the red cells, but no specific antibodies were identified. A positive DAT is a nonspecific finding.
Although the eluate studies were negative, the above findings of an anti-K antibody, the transfusion of a
Kell positive unit, and a positive DAT may indicate a delayed hemolytic transfusion reaction. The patient
should be monitored for signs of hemolysis (LDH, indirect bilirubin, reticulocyte count, decreased
haptoglobin, falling hemoglobin).
All other common, clinically significant alloantibodies were ruled out on an antibody identification panel
If the patient requires transfusions in the future, fully cross-matched, ABO/Rh compatible units lacking
the K antigen will be provided. Approximately 90% of donor units lack the K antigen.
Resident or Fellow , MD
47
Consults for Pediatric BMT Patients
Consults must be written for stem cell transplant patients when there are scheduled to undergo
allogeneic or autologous transplant or when their blood type changes. These consults should include the
transfusion restrictions for all blood components, and the tables below can be used to determine the
restrictions. Nurses transfusing these patients use these consults when checking blood components for
transfusion.
Consults are required for autologous transplants because incompatible plasma may put these
patients at increased risk for hepatic Veno-Occlusive Disease (VOD aka Sinusoidal Obstructive
Syndrome (SOS)). These restrictions are only valid for 2 months, after which the patients are no-longer at
risk for VOD. The 2 month time-frame for the restriction should be incorporated in the consult. A second
consult will not be required.
The resident will know when a transplant is scheduled when a copy of the transplant physician’s
order is in the resident in-box. The resident will know when a blood type changes when the appropriate
form is placed in the resident in-box.
The relevant Children’s policies are at the follow the sample consults and are #1.5 in the Policy
Book and #2.1 in the Serology Testing SOP Manual.
Sample Consults
Pre-Transplant (Autologous) or something similar for Allogeneic where donor and recipient are same
blood type:
Jane Doe is scheduled for an autologous Hematopoietic Progenitor Cell Transplant on date. Her
donor’s blood type is A+. For two months following the transplant, the following are acceptable blood
components for transfusions:
Red Cells (must be irradiated): A
Platelets (must be irradiated): A, AB
O (if concentrated)
B (if concentrated)
FFP: A, AB
All blood components can be from Rh+ or Rh- donors.
Starting two months following the transplant, there will be no need to concentrate platelets.
Pre-Transplant (Allogeneic).
Jane Doe is scheduled for a Hematopoietic Progenitor Cell Transplant on date. Her blood type is
O+. Her donor’s blood type is A+. Once she receives the transplant, the following are acceptable blood
types for transfusions:
Red Cells (must be irradiated): O
Platelets (must be irradiated): A, AB
O (if concentrated)
B (if concentrated)
FFP: A, AB
All blood components can be from Rh+ or Rh- donors.
Post-Transplant (Allogeneic, months later)
48
Jane Doe, who was originally O+, received a Hematopoietic Progenitor Cell Transplant from a
donor of type A+ on 11/15/04. She has now converted to A+ with no evidence of antibodies to A in her
serum. She can now receive blood component transfusions of the following types:
Red Cells (must be irradiated): O, A
Platelets (must be irradiated): A, AB,
O (if concentrated)
B (if concentrated)
FFP: A, AB
All blood components can be from Rh+ or Rh- donors.
49
SELECTION OF PRODUCTS DURING CONVERSION PERIOD
Rh Guidelines (implemented day of transplant)
All patients can receive platelets from an Rh(D)+ donor. Rh Immune Globulin is not used in the posttransplant setting.
ABO Guidelines (implemented the day of transplant)
Select products based on table below:
Single donor/
Autologous
transplant
selection
Recipient
Donor
A
A
A
Red Cells
Platelets
Plasma
A or O
A or AB or B concentrated or O
concentrated
A or AB
O
O
A or AB or B concentrated or O
concentrated
A or AB
A
B
O
AB or A concentrated or B
concentrated or O concentrated
AB
A
AB
A or O
AB or A concentrated or B
concentrated or O concentrated
AB
B
B
B or O
B or AB or A concentrated or O
concentrated
B or AB
B
O
O
B or AB or A concentrated or O
concentrated
B or AB
B
A
O
AB or A concentrated or B
concentrated or O concentrated
AB
B
AB
B or O
AB or A concentrated or B
concentrated or O concentrated
AB
Continued on next page
50
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appear here., Continued
Single donor/Autologous transplant selection (continued)
Recipient Donor
Red Cells
Platelets
Plasma
AB
AB
AB or A
or B or O
AB or A concentrated or B
concentrated or O concentrated
AB
AB
O
O
AB or A concentrated or B
concentrated or O concentrated
AB
AB
B
B or O
AB or A concentrated or B
concentrated or O concentrated
AB
AB
A
A or O
AB or A concentrated or B
concentrated or O concentrated
AB
O
O
O
O or A or B or AB
O
A
O
A or AB or B concentrated or O
concentrated
A or AB
O
B
O
B or AB or A concentrated or O
concentrated
B or AB
O
AB
O
AB or A concentrated or B
concentrated or O concentrated
AB
O or A
or B or
AB
Continued on next page
51
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appear here., Continued
Select products based on table below:
Double donor
transplant
selection
Recipient
Donors
Red
Cells
Platelets
Plasma
A
A,A
A or O
A or AB or B concentrated
or O concentrated
A or AB
A
O,O
A,O
O
A or AB or B concentrated
or O concentrated
A or AB
A
B,B
B,O
B,AB
AB,O
A,B
O
AB or A concentrated or B
concentrated or O
concentrated
AB
A
AB,AB
A,AB
A or O
AB or A concentrated or B
concentrated or O
concentrated
AB
B
B,B
B or O
B or AB or A concentrated
or O concentrated
B or AB
B
O,O
B,O
O
B or AB or A concentrated
or O concentrated
B or AB
B
A,A
A,O
AB,O
A,B
A,AB
O
AB or A concentrated or B
concentrated or O
concentrated
AB
B
AB,AB
B,AB
B or O
AB or A concentrated or B
concentrated or O
concentrated
AB
Continued on next page
52
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appear here., Continued
Error! Use the
Home tab to
apply Block
Label to the text
that you want to
appear here.
(continued)
Recipient
Donors
Red Cells
Platelets
Plasma
AB
AB,AB
AB or A
or B or O
AB or A concentrated or B
concentrated or O
concentrated
AB
AB
O,O
A,B
O,B
O,AB
O
AB or A concentrated or B
concentrated or O
concentrated
AB
AB
B,B
B,AB
B or O
AB or A concentrated or B
concentrated or O
concentrated
AB
AB
A,A
A,O
A,AB
A or O
AB or A concentrated or B
concentrated or O
concentrated
AB
O
O,O
O
O or A or B or AB
O or A
or B or
AB
O
A,A
O,A
O
A or AB or B concentrated
or O concentrated
A or AB
O
B,B
O,B
O
B or AB or A concentrated
or O concentrated
B or AB
O
AB,AB
A,B
A,AB
O,AB
B,AB
O
AB or A concentrated or B
concentrated or O
concentrated
AB