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Red Blood Cell

Transfusion
A Pocket Guide for the Clinician

Robert Weinstein, MD
University of Massachusetts Medical School
November 2016
Adapted from Red Blood Cell Transfusion:
A clinical practice guideline from the
AABB, Clinical Practice Guidelines
from the AABB: Red blood cell
transfusion thresholds and storage,
and additional sources
Red Blood Cells as a Therapeutic Product Irradiation Prevention of TA-GVHD in certain Radiation dose: 2500
circumstances cGy to center of
Appropriate uses of red blood cell (RBC) transfusion product
Donor categories
Treatment of symptomatic anemia Gamma or
Product donated by family member
X-irradiation
Prophylaxis in life-threatening anemia Product from HLA-selected donor
Shelf life of irradiated
Restoration of oxygen-carrying capacity in case of hemorrhage Products from directed donors
product: up to 28
RBCs are also indicated for exchange transfusion whose relationship to recipients
days unless original
w Sickle cell disease family has not been established
expiration date is
w Severe parasitic infection (malaria, babesiosis) Pediatric practice sooner
w Severe methemoglobinemia Intrauterine transfusion (IUT) NB: Supernatant K+
w Severe hyperbilirubinemia of newborn Exchange or simple transfusion in may be higher than
neonates if prior IUT usual
RBC transfusion is not routinely indicated for pharmacologically treatable Congenital immune deficiency
Allogeneic HPC
anemia such as: states
transplant recipient:
Iron deficiency anemia Acute leukemia: HLA-matched or Start with initiation of
Vitamin B12 or folate deficiency anemia family-donated products conditioning regimen
Continue throughout
Dosage and administration Allogeneic hemopoietic progenitor cell period of GVHD
One unit of RBC will raise the hemoglobin of an average-size adult (HPC) transplant recipient prophylaxis
by ~1 g/dL (or raise HCT ~3%) Allogeneic HPC donor 7 days prior to, Usually for at least
ABO group of RBC products must be compatible with ABO group of or during, HPC harvest 6 months
recipient Until lymphocytes
Autologous HPC recipient are > 1 x 109/L
RBC product must be serologically compatible with the recipient
Hodgkin disease Indefinitely if
(see Pretransfusion Testing). Exceptions can be made in
treated for chronic
emergencies (see Emergency Release of Blood Products). History of treatment with purine GVHD
Rate of transfusion analogues and related drugs
w Transfuse slowly for first 15 minutes Fludarabine Autologous HPC
2CDA (Cladribine) recipient
w Complete transfusion within 4 hours (per FDA)
Deoxycoformycin (Pentostatin) 7 days prior to, and
Clofarabine (Clolar) during, harvest
Major Red Cell Products for Transfusion Bendamustine (Treanda) Initiation of
Nelarabine (Arranon) conditioning
Most RBC products are derived by collection of 450-500 (10%) mL of whole blood through 3 months
from volunteer donors and removal of the plasma by centrifugation (see History of treatment with post transplant (6
Table 1). After removal of the plasma, the resulting product is red blood cells alemtuzumab (anti-CD52) months if TBI was
(referred to informally as packed red blood cells). Aplastic anemia on rabbit anti- used)
thymocyte globulin
The most commonly available US RBC product has a 42-day blood bank
shelf life and HCT 55-65%.
Pretransfusion Testing
Table 1. Special Processing of RBC for Transfusion
Prevents incompatible red cell transfusion
Process Indications Technical
Compatibility of donor red cells and recipient plasma
Considerations
Avoid immune hemolytic transfusion reactions in the recipient
Leukocyte Decrease risk of recurrent febrile, Most commonly
Reduction nonhemolytic transfusion reactions achieved by filtration
Pretransfusion blood sample from the intended recipient
Decrease risk of cytomegalovirus Usually soon Usually EDTA tube (plasma and red cells)
(CMV) transmission (marrow after collection Proper labeling of the sample
transplant) (prestorage) w 2 independent patient identifiers
Decrease risk of HLA-alloimmunization May be performed w Identity of the phlebotomist
Does not prevent transfusion- at bedside w Date and time of sample collection
associated graft-versus-host disease <5x106 leukocytes per
w Sample rejected without these
(TA-GVHD) product (per FDA)
Age of the sample
Washing Decrease risk of anaphylaxis in Wash fluid is 0.9% w Up to 3 days if hospital inpatient or, in past 3 months, recipient
(removes IgA-deficient patient with anti-IgA NaCl dextrose - Has been pregnant
residual antibodies Shelf life of washed - Has been transfused
plasma) Decrease reactions in patients with RBCs
history of recurrent, severe allergic 24 hours at 1-6C
- Has uncertain history of either
or anaphylactoid reactions to blood 4 hours at 20-24C w Longer (often 12 weeks, according to hospital policy) for
product transfusion May lose 20% of outpatient
red cells in washing pre-op testing if negative history within 3 months
process
Table 2. Pretransfusion Testing Blood bank unable to determine presence or absence of underlying
alloantibodies
Test Purpose Reagents Time
All RBC units are crossmatch-incompatible
ABO Group & Determine if recipients Test recipients red ~25 min
Rh Type blood group Rho(D) is cells with anti-A, anti-B, Balance of risks
positive or negative anti-D; test recipients Severe anemia requiring transfusion support
plasma with A1* and Possibility of hemolytic transfusion reaction due to undiagnosed
B cells underlying alloantibodies
Antibody Detect unexpected, Test recipients plasma ~50 min Principles of approach to this situation
Screen clinically significant with phenotyped Communication between bedside clinician and transfusion service
(non-ABO) anti-RBC reagent RBCs
physician is essential
antibodies in recipients
plasma w Obtain careful history of prior transfusion or pregnancy
- If history negative, probably safe to transfuse ABO-compatible
Antibody Identify specificity of Test recipients plasma Varies: RBCs
Identification anti-RBC antibody if with many reagent Hours
- If history positive or uncertain, assess risk:benefit of delaying
antibody screen is pos RBCs to days
transfusion to complete testing
Immediate Ensure ABO Test recipients plasma ~10 min w Assess how long it may take for blood bank or reference lab to
Spin compatibility between with sample of red cells complete pretransfusion testing
Crossmatch recipients plasma and from product chosen w Agree on best approach to choosing among incompatible RBC
(when antibody RBC product chosen for transfusion
screen is for transfusion
units (transfusion physician will advise)
negative) Attempt to mitigate need for immediate transfusion: bed rest,
oxygen
Full Serological Ensure full serological Test recipients plasma Up to
Crossmatch compatibility between with sample of red an hour Ultimately, do not deprive a patient with autoimmune hemolytic anemia
(when antibody recipients plasma and cells from product of a needed, lifesaving transfusion
screen is RBC product chosen chosen for transfusion. Autoantibody will shorten survival of transfused RBCs and patients
positive) for transfusion Includes extra endogenous RBCs to a similar extent
incubations (e.g. at
Most undetected alloantibodies will cause delayed hemolytic
37C and with Coombs
reagent). transfusion reactions
w May be misdiagnosed as worsening of autoimmune hemolysis
Electronic Match ABO/Rh Validated blood bank ~10-15 w Not usually life-threatening
Crossmatch compatible RBC from computer system. min Bedside team must be hypervigilant for acute intravascular
inventory with patient
(not universally whose ABO/Rh status
hemolytic reaction during transfusion (see Adverse Effects of
available) has been confirmed Transfusion)
and who has no history
of, and negative testing Red Blood Cell Transfusion
for, RBC alloantibodies
Table 3. RBC Transfusion Recommendations* for Hospitalized,
*A1 is the most common subgroup of Group A Hemodynamically Stable Patients in Specific Clinical Situations
Clinical Potential Transfusion Strength of Quality of
Emergency Release of Blood Products Situation Threshold Recom- Supporting
mendation Evidence
An emergency release of blood products is warranted when the
clinical setting precludes waiting for completion of pretransfusion and Adult Inpatients, Hgb** 7 gm/dL Strong Moderate
compatibility testing. Examples include: Hemodynamically
Severe, ongoing life-threatening hemorrhage Stable
Life-threatening anemia ICU Patients, Hgb 7 gm/dL Strong High
What you should do: Hemodynamically
Stable (adult or
Notify blood bank of need for emergency release of RBCs pediatric)
Complete hospitals emergency release form
w Documents your declaration of a transfusion emergency Postoperative Hgb 8 gm/dL Strong Moderate
w U.S. federal regulations require 2 specific items on the form Orthopedic or or for symptoms
Cardiac Surgery
- Statement of the nature of the emergency (e.g. massive GI
Patients
hemorrhage)
- Signature of MD or equivalent; (PA, NP, RN, etc. cannot sign) Cardiovascular Hgb 8 gm/dL Strong Moderate
Send patient blood sample to blood bank ASAP (before emergency Disease or for symptoms
transfusion begins, if possible) Acute Coronary AABB does not Uncertain Very Low
Syndrome recommend for or against
What youll get from the blood bank (depending on how much testing has a liberal or restrictive RBC
already been performed): transfusion strategy
Uncrossmatched RBCs (ABO group-specific if determined on a
current blood specimen) All Patients Guided by symptoms as Weak Low
well as by Hgb level
Group O RBCs if blood bank has not documented patients ABO
group on a fresh blood sample *Table adapted from: Red Blood Cell Transfusion: A clinical practice
w Rh neg depending on availability and hospital policy, if patients Rh guideline from the AABB. Ann Intern Med 2012;157:49-58 and Clinical
status is unknown practice guidelines from the AABB: Red blood cell transfusion thresholds
Blood bank will retrospectively crossmatch all emergently issued units and storage. JAMA. doi:10.1001/jama.2016.9185.
when it receives the patients testing sample **Hgb=Hemoglobin level
Cannot be generalized to the preoperative setting, where expected
Blood bank will begin issuing type specific and crossmatched products surgical blood loss must be taken into account in transfusion decision
when testing is complete making.
Chest pain, orthostatic hypotension or tachycardia unresponsive to
Transfusion of Incompatible RBCs fluids, or congestive heart failure.
There remains some uncertainty regarding the risk of perioperative
Clinical scenario: severe warm (or cold) autoimmune hemolytic anemia myocardial infarction with a restrictive transfusion strategy.
Patients plasma autoantibody reacts with all of the blood banks
reagent red cells
Adverse Effects of Transfusion Rating System and Implications of Recommendations
The most clinically important adverse effects of transfusion in medical As indicated in this guide, evidence-based recommendations from the
patients are infectious or immunological phenomena. The most AABB guidelines are separately rated according to the strength of the
significant infectious risks are addressed during the donor screening recommendation (strong, moderate, or weak) and the quality of the
process, and most blood centers employ bacteriological surveillance supporting evidence (high, moderate, low, or very low). These ratings are
measures on certain blood products. intended to have the following implications (adapted from GRADE):
Table 4. Some Infectious Risks of Blood Transfusion (all products) High-quality evidence 34 Low-quality evidence

Transfusion-Transmitted Residual Risk Per Transfused Strong Recommendation can apply to Recommendation
Infection Component recommendation most patients in most circum- may change when
stances. higher quality evidence
HIV 1 in 1,467,000
2 becomes available.
Hepatitis C 1 in 1,149,000
Weak The best action may differ Other alternatives may
Hepatitis B 1 in 282,000 recommendation depending on circumstances or be equally reasonable.
patient or societal values.
West Nile Virus Uncommon
Cytomegalovirus 50-85% of donors are carriers. Leukocyte References
reduction is protective. This pocket guide is adapted from Carson JL, Grossman BJ, Kleinman S
Bacterial Infection 1 in 2-3,000 (mostly platelets) et al., Red Blood Cell Transfusion: A clinical practice guideline from the
AABB, Ann Intern Med 2012;157:49-58 and Carson, JL, Guyatt G, Heddle
Parasitic Diseases Relatively uncommon
Babesiosis, Chagas, Malaria NM, et al., Clinical Practice Guidelines from the AABB: Red blood cell
transfusion thresholds and storage, JAMA, published online October 12,
Other Important Adverse Effects of Blood Transfusion 2016. It also presents selected information from: Roback JD, Grossman,
BJ, Harris T, Hillyer CD eds. Technical Manual, 17th Edition. Bethesda, MD:
For any of the following, except allergic (uticarial) reactions, stop
AABB Press 2011 and Circular of Information for the Use of Human Blood
transfusion and return remaining product to blood bank with
and Blood Components. AABB, ABC, ARC, ASBP. Revised December,
transfusion reaction report:
2009. GRADE adaptation based on Schnemann HJ et al., An official ATS
Acute hemolytic transfusion reaction (AHTR): Preformed antibodies statement: grading the quality of evidence and strength of recommenda-
to incompatible product (1:76,000). ABO incompatibility (1:40,000). tion in ATS guidelines and recommendations, Am J Respir Crit Care Med
Sometimes fatal (1:1.8x106). Presents with chills, fever, hypotension, 2006;174(5):60514.
hemoglobinuria, renal failure, back pain, DIC. Keep IV open with normal
saline. Keep urine output >1 mL/kg/hour. Pressors PRN. Treat DIC.
Delayed HTR: Anamnestic immune response to incompatible red
cell antigen. May present with fever, jaundice, falling hemoglobin,
newly positive antibody screen in blood bank. Occurs 1-2 weeks after
transfusion. Identify offending antibody in blood bank. Transfuse PRN American Society of Hematology
with compatible RBCs. 2021 L Street NW, Suite 900
Washington, DC 20036
Febrile non-HTR: 0.1-1.0%. Due to preformed anti-WBC antibodies in
www.hematology.org
recipient. Risk minimized with leukocyte-reduced products. 1C (2F)
rise in temperature within 2 hours of start of transfusion with no other
explanation for fever. Acetaminophen premedication if reactions are
recurrent.
Allergic (urticarial) reactions: 1-3%. Antibody to donor plasma
proteins. Presents with urticaria, pruritus, flushing, mild wheezing.
Pause transfusion, administer antihistamines; may resume transfusion
if reaction resolves, but still report reaction to blood bank. How to Use This Pocket Guide
Anaphylactoid/anaphylactic: 1:20,000-50,000. Caused by antibody ASH pocket guides are primarily intended to help clinicians make deci-
to donor plasma proteins (IgA, haptoglobin, C4). Hypotension, urticaria, sions about diagnostic and treatment alternatives. These guidelines are
bronchospasm, angioedema, anxiety. Rule out hemolysis. Administer not intended to serve or be construed as a standard of care. Clinicians
epinephrine 1:1000 0.2-0.5 ml SC, antihistamines, corticosteroids. must make decisions on the basis of the unique clinical presentation of
an individual patient, ideally through a shared process that considers the
Transfusion-related acute lung injury (TRALI): ~1:10,000.
patients values and preferences with respect to all options and their pos-
Preformed HLA or neutrophil antibodies in donor product. Hypoxemia,
sible outcomes. Decisions may be constrained by realities of a specific
hypotension, bilateral pulmonary edema, transient leucopenia, and
clinical setting, including but not limited to institutional policies, time
fever within 6 hours of transfusion. 10-20% fatal. Supportive care.
limitations, or unavailability of treatments. ASH pocket guides may not in-
Defer implicated donors.
clude all appropriate methods of care for the clinical scenarios described.
Transfusion-associated graft-versus-host disease: Rare but almost As science advances and new evidence becomes available, these
always fatal. Immunosuppressed recipient receives transfusion pocket guides may become obsolete. Following these guidelines cannot
from HLA-similar donor (usually a family member). Pancytopenia, guarantee successful outcomes. ASH does not warrant or guarantee any
maculopapular rash, diarrhea, hepatitis presenting 1-4 weeks after products described in these guidelines.
transfusion. Prevented by irradiating blood products.
Dr. Weinstein declares no competing financial interests.
Transfusion-associated circulatory overload (TACO): Approximately
To order this and other pocket guides, go to www.hematology.org/Store.
1% of transfusions. New onset or exacerbation of acute respiratory
distress (dyspnea, orthopnea, count) 3-6 hours after transfusion. May 2016 The American Society of Hematology
be associated with elevated BNP, elevated central venous pressure, All rights reserved. No part of this publication may be reproduced, stored
left heart failure, positive fluid balance, pulmonary edema on chest in a retrieval system, or transmitted in any form or by any means, elec-
x-ray. Risk factors include cardiac or renal dysfunction, female gender, tronic or mechanical, including photocopy, without prior written consent
age > 60 years, severe anemia with volume expansion, positive fluid of the American Society of Hematology.
balance, transfusion of multiple products. Mortality rate 1.4-8.3%.
Management includes stopping transfusion and other fluids, sit patient For expert consultation on red blood cell transfusion and other he-
up, supplemental oxygen, diuretic therapy. matologic diseases, submit a request to the ASH Consult a Colleague
program at
www.hematology.org/Consult (ASH members only).

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