Transfusion medicine
Transfusion reaction
Acute hemolytic transfusion reaction (AHTR)

Topic Completed: 1 July 2017

Revised: 9 May 2019

Copyright: 2002-2019,, Inc.

PubMed Search: Acute hemolytic transfusion reaction (AHTR)

Faisal Mukhtar, M.B.B.S.
J. Peter R. Pelletier, M.D.
Page views in 2018: 1,119
Page views in 2019 to date: 561
Cite this page: Mukhtar F, Pelletier JPR. Acute hemolytic transfusion reaction (AHTR). website. Accessed June 20th, 2019.
Definition / general
  • Must occur within 24 hours of blood component administration and often during transfusion itself
  • Mostly due to transfusion of incompatible packed RBCs (pRBCs) but may also result from incompatible plasma containing components such as fresh frozen plasma (FFP) or platelets
  • Usually due to "mistransfusion" of ABO incompatible pRBCs
    • Transfusion service error
      • Typing
      • Labeling
      • Crossmatching
    • Clinical service error
      • Wrong patient's sample
      • Wrong unit transfused (at the bedside) to a patient
      • 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 1:1.8 million and correlates with the amount of incompatible blood transfused (Blood 2009;113:3406)
  • Causes 10 – 30 deaths in US each year
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 anti A or anti B antibodies of IgM type → fixation of complement → formation of membrane attack complex → 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 nitric oxide (NO) → vasoconstriction
    • RBC stroma → activates platelets and coagulation cascade → DIC
    • RBC stroma → damages 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 on pRBC unit)
  • Return implicated blood bag, tags and attached administration set to blood bank
  • Send samples for confirming patient's ABO type, visual check for hemoglobinemia (pink or red serum / plasma) and direct antiglobulin test (DAT)
  • Retype pretransfusion 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 per hour) can use diuretics (furosemide)
  • Administer low dose dopamine for hypotension (1 – 5 µg/kg per 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 barcoding 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, anti B or anti A,B in plasma containing products (platelets, FFP) → hemolysis of patient's own 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 smaller patients (such as neonate, infants or children)
  • 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
  • During inventory shortages, washed or volume reduced platelets can be transfused but are usually NOT recommended, because it leads to loss of 33% of platelets and platelet activation during the processing
Case reports
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