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Transfusion medicine

Tranfusion reaction

Acute hemolytic transfusion reaction (AHTR)

Reviewer: Huy Phu Pham, M.D. (see Reviewers page)
Revised: 4 December 2011, last major update September 2011
Copyright: (c) 2007-2011, PathologyOutlines.com, Inc.


● By definition, must present within 24 hours of transfusion
● Due to transfusion of incompatible packed RBCs or significant incompatible plasma
● Usually due to “mistransfusion” of ABO incompatible pRBCs (transfusion service error - typing, labeling, crossmatching - or clinical service error, wrong patient’s sample, wrong unit on patient) or transfusion of incompatible pRBCs (could be ABO incompatible to patient’s antibodies)


● True incidence is unknown
● Up to 47% of cases of ABO-incompatible mistransfusion had no adverse effect
● Less than 10% of ABO-incompatible transfusions cause fatal outcome
● Risk of death from ABO incompatible transfusion is estimated to be 1:1.5 million, and correlates with the amount of incompatible blood transfused
● Causes 10–30 deaths in US each year (Merck Manual)

Clinical manifestations

● Fever (important) – early sign of AHTR – need to monitor vital signs frequently during the initial minutes of transfusion
● Anxiety, sense of doom
● Nausea, vomiting
● Pain at infusion site
● Diffuse bleeding
● Flank and back pain
● Hyper- or hypotension
● Hemoglobinuria


Intravascular hemolysis:
● ABO-incompatible: pre-existing natural occurring antibodies of IgM type --> fixation of complement --> red cell lysis
● Some IgG antibodies can also fix complement --> mild to fatal AHTR
● Usually occurs when mistransfusion of antigens in Kell, Duffy and Kidd systems

DIC, shock and renal failure:
● Free hemoglobin from hemolysis --> binds to NO --> vasoconstriction
● RBC stroma --> activates platelets and coagulation cascade --> DIC
● RBC stroma is also toxic to renal tubules --> renal failure

Management and workup

● Stop the transfusion
● Contact the transfusion service immediately
● Check for clerical error (i.e. patient identity and the patient identity of pRBC unit)
● Send samples for confirming patient’s ABO type, visual check for hemoglobinemia (most sensitive test) and direct antiglobulin test (DAT)
● Retype pre-transfusion sample and blood unit for ABO
● Send clinical tests, including CBC, chemistry, bilirubin, haptoglobin (Eur J Clin Invest 2006;36:202), LDH, UA with microscopic examination for hemoglobinuria and coagulation
● Provide good supportive care
● Maintain good urine output (> 1ml/kg/hr) – can use diuretics (mannitol)
● Administer low dose dopamine for hypotension (1–5 mcg/kg/min)
● Manage DIC and hemorrhage as clinically indicated


● Strictly adhere to the protocol to prevent mislabeled and miscollected samples
● Always perform bedside check before administering blood products
● Other innovations include bar-coding of blood components and patient ID
● Educate physicians and nurses regarding transfusion practice

Transfusion of significant incompatible plasma

● Occurs less frequently
● Due to minor ABO mismatch – transferring of donor anti-A or anti-B in plasma-contained products --> hemolysis of patient’s ABO incompatible RBCs
● Most often due to transfusion of out-of group platelet (most commonly group O platelets to group A patient, Arch Pathol Lab Med 2007;131:909); also donor with high titer of anti-A (> 1000), transfusion of large volume of plasma into a small patient (such as neonate)
● Clinical symptoms are identical to transfusion of incompatible pRBCs
● Can prevent by screening for anti-A titer (not currently done in the US)
● Recommended to increase inventory to avoid out-of-group platelet transfusion, but this is difficult
● Washed platelets are NOT recommended, because it leads to loss of 33% of platelets and platelet activation

Case reports

Due to antibodies:
● ABO incompatible platelet products (Am J Clin Pathol 1999;111:202)
● In a baby (J Clin Apher 2005;20:225)
● Anti-Bg HLA antibodies (Transfusion 2003;43:753)
● Anti-Coa (Immunohematol 2001;17:45 )
● Anti-Dombrock(a) (Transfusion 2006;46:244)
● Anti-Fy3 in a non sickle cell disease patient (Immunohematol 2005;21:48)
● Anti-IH in a patient with sickle cell disease (Transfusion 2000;40:828)
● Anti-Jk(a) not detected by polybrene screen (Ann Clin Lab Sci 2006;36:101)
● Anti-Jr(a) (Transfusion 2004;44:197)
● Anti-P1 (Transfusion 1998;38:373)

Due to non-antibodies:
● Chimeric red cells in a donor who was a twin (Transfusion 2003;43:1449)
● Sickle cell disease (Transfusion 2001;41:323)

End of Transfusion Medicine > Tranfusion reaction > Acute hemolytic transfusion reaction (AHTR)

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