Transfusion Reaction, Hemolytic



  • Every year, >5 million people in the United States receive a transfusion.
  • Although it provides benefits, transfusion of blood products can result in a variety of serious complications, termed transfusion reactions.
  • Hemolytic reactions are categorized by mechanism and consequence of the reaction:
    • Immune mediated
      • Intravascular hemolysis
      • Extravascular hemolysis
    • Non–immune mediated
      • Contact with hyper- or hypotonic fluids
      • Temperature changes
      • Mechanical forces (e.g., mechanical heart valves)

Pediatric Considerations
Reaction is greater and the outlook poorer in the very young.

Geriatric Considerations
Higher risk of complications among the elderly


  • Frequency of immunologic reaction per unit of blood
    • Allergic: 1:100
    • Febrile: 1:100
    • Delayed hemolytic: 1:1,600
    • Acute hemolytic: 1:50,000
    • Fatal hemolytic reaction: 1:500,000
  • Infectious complications per unit of blood
    • Hepatitis B virus: 1:81,000
    • Human T-lymphotropic virus, type 1: 1:642,000
    • Hepatitis C virus: 1:1.6 million
    • HIV, type 1: 1:2 million

In 1 series of 265 documented emergency transfusions without crossmatching, only 1 hemolytic reaction was reported (0.4%).

Etiology and Pathophysiology

  • Acute hemolytic transfusion reactions (AHTRs)
    • When ABO-incompatible blood is transfused, donor erythrocytes are destroyed by the recipient’s preformed antibodies, causing intravascular hemolysis.
    • Most commonly occurs when group O recipients receive non–group-O blood; IgM antibodies to group A and B antigens fix complement and cause rapid hemolysis.
    • Misidentification of blood product or patient, often because of clerical error
  • AHTRs
    • Patient has preformed IgM isoantibodies (also called isohemagglutinins) reactive to protein on surfaces of RBCs.
    • Isoantibodies trigger and fix the complement system to surfaces of RBCs. C3a and C5a activate white blood cells to release inflammatory cytokines such as IL-1, IL-6, IL-8, and TNF-α.
    • Complement cascade leads to rapid intravascular destruction of transfused cells.
  • Delayed hemolytic transfusion reactions (DHTRs) can occur in patients sensitized to an antigen by prior transfusions or pregnancy. It may be difficult to detect because antibody titer falls after initial sensitization and reaction occurs 2 to 10 days after transfusion.
  • DHTRs
    • Pathophysiology of DHTRs is the subject of intense study.
    • Recent research implicates a similar pathway to IgG-mediated anaphylactic reaction.
    • FcγRs on the patient’s macrophages react with IgG-coated transfused RBCs.
    • Resulting cascade of proinflammatory cytokines and platelet-activating factor

No known genetic pattern

Risk Factors

  • Patients with chronic requirements for blood transfusions
    • Sickle cell anemia
    • β-Thalassemia major
  • Patients requiring massive transfusion
    • Trauma
    • Organ transplantation

General Prevention

  • Reduce risks of clerical and administrative error (1)[B].
    • At a minimum, two practitioners should verify blood product and patient identity match.
    • Obtain detailed history of patient’s responses to previous blood product transfusion.
    • Use matched blood whenever possible.
    • If matched blood is not available, thoroughly check universal blood for agglutination titer.
    • Blood bank should screen consistently for bacteria and viruses.
  • Reduce number of allogeneic transfusions.
    • Carefully consider the risk-to-benefit analysis of every transfusion.
    • Treatment with recombinant human erythropoietin may reduce transfusion requirement for patients with chronic kidney disease.
  • Peritransfusion clinical practice
    • Observe patient closely during transfusion with serial vital signs.
    • Avoid prophylactic antipyretics.
    • Use genotype-specific RBCs in sickle cell anemia.
    • Consider leukocyte-depleted blood in people with history of recurrent febrile reactions.
    • Case reports have indicated that prophylactic treatment with rituximab and eculizumab may prevent DHTRs and AHTRs, respectively; however, higher level evidence is lacking.

Commonly Associated Conditions

  • Disseminated intravascular coagulation (DIC)
  • Shock
  • Acute renal failure

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