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Home , AABB, Blood bank, Blood transfusion, Packed red blood cells

Red Transfusion A Pocket Guide for the Clinician

Robert Weinstein, MD University of Massachusetts Medical School November 2016 Adapted from 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 Prevention of TA-GVHD in certain Radiation dose: 2500 circumstances cGy to center of product Appropriate uses of red blood cell (RBC) transfusion Donor categories Gamma or • Treatment of symptomatic Product donated by family member X-irradiation • Prophylaxis in life-threatening anemia Product from HLA-selected donor of irradiated Products from directed donors • Restoration of -carrying capacity in case of hemorrhage product: up to 28 whose relationship to recipient’s • RBCs are also indicated for days unless original family has not been established w Sickle cell expiration date is w Severe parasitic (, ) 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 states anemia such as: transplant recipient: • 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 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 9 • RBC product must be serologically compatible with the recipient are > 1 x 10 /L (see Pretransfusion Testing). Exceptions can be made in Hodgkin disease Indefinitely if treated for chronic emergencies (see Emergency Release of Blood Products). History of treatment with purine GVHD • Rate of transfusion analogues and related w Transfuse slowly for first 15 minutes Autologous HPC w Complete transfusion within 4 hours (per FDA) 2CDA (Cladribine®) recipient 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 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 “”). on rabbit anti- used) thymocyte globulin The most commonly available US RBC product has a 42-day 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 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 6 associated graft-versus-host disease <5x10 leukocytes per w Sample rejected without these (TA-GVHD) product (per FDA) • Age of the sample Washing Decrease risk of 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 Shelf life of washed - Has been transfused plasma) Decrease reactions in patients with RBCs - Has uncertain history of either history of recurrent, severe allergic 24 hours at 1-6°C or anaphylactoid reactions to blood 4 hours at 20-24°C w Longer (often 1–2 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 recipient’s Test recipient’s 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 recipient’s • Severe anemia requiring transfusion support * plasma with A1 and • Possibility of hemolytic transfusion reaction due to undiagnosed B cells underlying alloantibodies Detect unexpected, Test recipient’s plasma ~50 min Principles of approach to this situation Screen clinically significant with phenotyped • between bedside clinician and transfusion service (non-ABO) anti-RBC “reagent” RBCs physician is essential antibodies in recipient’s plasma w Obtain careful history of prior transfusion or pregnancy - If history negative, probably safe to transfuse ABO-compatible Antibody Identify specificity of Test recipient’s 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 recipient’s 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 recipient’s plasma and from product chosen w Agree on best approach to choosing among incompatible RBC (when antibody RBC product chosen for transfusion units (transfusion physician will advise) screen is for transfusion negative) • Attempt to mitigate need for immediate transfusion: bed rest, oxygen Full Serological Ensure full serological Test recipient’s plasma Up to Crossmatch compatibility between with sample of red an hour Ultimately, do not deprive a patient with autoimmune (when antibody recipient’s 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 patient’s positive) for transfusion Includes extra endogenous RBCs to a similar extent incubations (e.g. at • Most undetected alloantibodies will cause delayed hemolytic 37°C and with Coombs reagent). transfusion reactions w May be misdiagnosed as worsening of autoimmune 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, Hemodynamically Stable Patients in Specific Clinical Situations *A1 is the most common subgroup of Group A 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 hospital’s “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 - 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 you’ll 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 • Group O RBCs if blood bank has not documented patient’s ABO well as by Hgb level 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 patient’s 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 patient’s 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 or 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 with a restrictive transfusion strategy. • Patient’s plasma autoantibody reacts with all of the blood bank’s 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 (all products) Low-quality evidence High-quality evidence 34 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. C 1 in 1,149,000 Weak The best action may differ Other alternatives may 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 ) 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 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 Schünemann 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):605–14. , renal failure, back pain, DIC. Keep IV open with normal . Keep urine output >1 mL/kg/hour. Pressors PRN. Treat DIC. Delayed HTR: Anamnestic to incompatible red cell . May present with fever, , 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 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. ≥1°C (2°F) 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 . Presents with urticaria, pruritus, flushing, mild wheezing. Pause transfusion, administer ; 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, , 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 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. patient’s 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 , 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). , 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).