Transfusion Reaction



  • Any acute or subacute adverse reaction that develops as a consequence of the administration of blood components
  • Types include the following:
    • Acute reactions: hemolytic, febrile, allergic, anaphylactic, septic, transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO)
    • Delayed reactions: delayed hemolytic, transfusion-associated graft-versus-host disease (TA-GVHD)
    • Late complications of transfusion: infection, alloimmunization, iron overload


  • 1% of pediatric blood product recipients develop some type of transfusion reaction.
  • Transfusion associated with death in 1 in 200,000 to 420,000 transfused units


  • Acute hemolytic transfusion reaction
    • Antigen–antibody interaction leads to complement activation on the surface of the transfused RBCs, resulting in acute intravascular hemolysis and vasomotor instability.
    • Usually ABO blood group incompatibility
    • Most commonly due to medical error
  • Febrile nonhemolytic transfusion reaction (FNHTR)
    • Cytokines released by leukocytes in the product
    • 40% of patients with one febrile reaction will have a subsequent one.
  • Urticarial (allergic)
    • IgE-mediated
    • Recipient allergic response to donor plasma proteins or other constituents of plasma
    • Sporadic and donor dependent
  • Anaphylactic
    • Overwhelming acute allergic reaction; can be mediated by anti-IgA formed by a recipient who is IgA deficient and receives blood products containing IgA
  • Bacterial sepsis
    • Intravascular infusion of viable bacteria and endotoxins leads to fever, chills, and/or acute septic shock.
    • Contaminated blood product; most commonly a platelet product near the end of shelf life
  • Delayed hemolytic transfusion reaction (DHTR)
    • Previously transfused patients who are sensitized to a minor blood group antigen, especially Jka or Jkb (Kidd antigen), develop an anamnestic response on reexposure.
    • Antibody is below detectable levels in antibody screen and crossmatch; after transfusion, titers rise (usually within 2 to 10 days) and extravascular hemolysis occurs.
    • Antileukocyte antibodies or neutrophil-activating factors in transfused product interact with recipient neutrophils, causing leukocyte aggregates that deposit in the lung.
    • Multiparous female donors with HLA sensitization often are implicated.
  • TACO
    • Circulatory overload leading to heart failure
    • Administration of an excessive volume of a blood product or infusion at an excessive rate
    • Patients with inherited or acquired T-cell immunodeficiency can develop TA-GVHD from transfused immunocompetent T cells.
    • Can also occur if the donor and recipient are related and share HLA types



  • Acute hemolytic
    • Fever/chills
    • Abdominal or flank pain
    • Pink or tea-colored urine
    • Tachycardia
    • Hypotension
    • Oliguria
    • Fever, chills 1 to 6 hours after transfusion
  • Urticarial
    • Urticaria
    • Flushing
    • Pruritus
  • Anaphylactic
    • Urticaria
    • Bronchospasm
    • Hypotension
  • Bacterial sepsis
    • Fever
    • Chills
    • Hypotension
  • DHTR
    • Fever
    • Malaise
    • Dark urine
    • Jaundice
    • Shock (rarely)
    • Renal failure 2 to 10 days after transfusion
    • Acute dyspnea, tachypnea, rales, decreased oxygenation within 6 hours of transfusion
  • TACO
    • Hypertension
    • Dyspnea
    • Rales
    • Cardiac arrhythmia
    • Fever
    • Rash
    • Diarrhea
    • Cough 4 to 30 days after transfusion

Diagnostic Tests and Interpretation

Initial Tests

  • Acute hemolytic
    • Direct Coombs test: positive
    • CBC: anemia
    • Urinalysis: hemoglobinuria
    • Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin split products: disseminated intravascular coagulation (DIC)
    • Direct Coombs test: negative or no change from pretransfusion
    • Immediate Gram stain of the product
    • Blood culture of the patient and product
    • All results should be negative; a diagnosis of exclusion
  • Urticarial
    • No specific testing
  • Anaphylactic
    • IgA level in recipient. If undetectable, test for anti-IgA antibody (of the IgE class).
  • Bacterial sepsis
    • Immediate Gram stain and blood culture of the transfused product: result positive for bacteria
  • DHTR
    • CBC: anemia
    • Bilirubin: elevated
    • Indirect Coombs test (antibody screen): positive
    • Direct Coombs test: positive (mixed field) if done early
    • Leukocyte antibody testing in the implicated donor(s)
  • Chest radiograph: increased pulmonary vascular markings or infiltrates for hypervolemia (TACO) and TRALI


General Measures

  • Acute hemolytic
    • Stop transfusion immediately.
    • Supportive care with hydration, pressors, and diuretics to maintain circulation and urine output
    • Stop transfusion.
    • Antipyretics (acetaminophen)
    • Demerol for severe chills and rigors
    • May resume transfusion if patient is stable and acute hemolytic transfusion reaction and bacterial sepsis are ruled out
  • Urticarial
    • Stop transfusion.
    • Antihistamine (diphenhydramine)
    • Steroids or epinephrine in severe reactions
    • Transfusion may be resumed if mild reaction.
  • Anaphylactic
    • Epinephrine
    • IV fluids, pressors
    • Respiratory support
  • Bacterial sepsis
    • Stop transfusion.
    • Fluids if hypotensive
    • Antibiotics to eradicate Staphylococcus and Gram negatives including Yersinia species
  • DHTR
    • Depends on degree of hemolysis; if profound, management as acute hemolytic reaction. If mild, no therapy may be needed.
    • Supportive care; usually resolves in 12 to 24 hours
  • TACO: diuretics (furosemide)
  • TA-GVHD: no treatment; almost always fatal
  • General prevention
    • Acute hemolytic
      • Proper labeling of blood specimens and products and adherence to procedures for correct identification of product and recipient will eliminate most acute hemolytic transfusion reactions.
    • FNHTR
      • Administration of leukodepleted blood products, especially for long-term transfused patients who have a high incidence of febrile transfusion reactions
      • No evidence to support premedication with acetaminophen or diphenhydramine to prevent FNHTR
    • Urticarial
      • Administration of washed erythrocyte products (in patients with repeated or severe allergic reactions)
      • No conclusive evidence to support premedication with antihistamines
    • Anaphylactic
      • If due to anti-IgA in an IgA-deficient recipient, provision of IgA-deficient products may be possible.
    • Bacterial sepsis
      • Sterile technique in blood collection, storage, and administration; inspection of product before transfusion
      • Bacterial screening of platelet products before they are transfused
    • DHTR
      • Appropriately performed antibody screen and crossmatch as pretransfusion testing
      • Check blood bank records for previous antibodies.
    • TRALI
      • Deferral of donors is implicated in proven TRALI cases.
    • TACO
      • Administer appropriate volumes (typically 10 to 15 mL/kg) at appropriate rate, usually over 3 to 4 hours unless hypovolemic or actively bleeding.
      • Patients with chronic anemia are euvolemic and should be transfused with smaller volumes over longer time periods.
    • TA-GVHD
      • Patients at risk (immunocompromised, neonates) must receive irradiated blood products.

Ongoing Care


  • Posttransfusion hepatitis: caused by hepatitis B or C viruses, others
  • AIDS: caused by HIV
  • Cytomegalovirus (CMV)
    • Symptomatic infection in patients with inherited or acquired immunodeficiency states, premature neonates
    • These individuals should receive CMV-safe products.
  • Other transfusion-transmissible infections
    • Epstein-Barr virus, syphilis, malaria, toxoplasmosis, human T-cell lymphotropic virus I (HTLV-I), Chagas disease, babesiosis, filariasis, West Nile virus, parvovirus B19
  • Alloimmunization
    • Formation of antibodies to erythrocyte, platelet, and HLA antigens can develop in some multiply transfused patients; may cause delays in pretransfusion testing, febrile transfusion reactions, DHTR, and platelet transfusion refractoriness
    • HLA alloimmunization may also affect eligibility and organ procurement for solid organ transplantation.
  • Iron overload
    • Long-term transfusion recipients will accumulate iron as a by-product of erythrocyte breakdown.
    • An iron-chelating drug will enhance its excretion.

Additional Reading

  1. Delaney M, Wendel S, Bercovitz RS, et al. Transfusion reactions: prevention, diagnosis, and treatment. Lancet. 2016;388(10061):2825–2836.  [PMID:27083327]
  2. Lindholm PF, Annen K, Ramsey G. Approaches to minimize infection risk in blood banking and transfusion practice. Infect Disord Drug Targets. 2011;11(1):45–56.  [PMID:21303341]
  3. Slonim AD, Joseph JG, Turenne WM, et al. Blood transfusions in children: a multi-institutional analysis of practices and complications. Transfusion. 2008;48(1):73–80.  [PMID:17894792]
  4. Tobian AA, King KE, Ness PM. Transfusion premedications: a growing practice not based on evidence. Transfusion. 2007;47(6):1089–1096.  [PMID:17524101]
  5. Vamvakas EC, Blajchman MA. Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention. Blood. 2009;113(15):3406–3417.  [PMID:19188662]



  • 999.80 Transfusion reaction, unspecified
  • 999.83 Hemolytic transfusion reaction, incompatibility unspecified
  • 999.89 Other transfusion reaction
  • 518.7 Transfusion related acute lung injury (TRALI)
  • 999.41 Anaphylactic reaction due to administration of blood and blood products
  • 999.70 Rh incompatibility reaction, unspecified
  • 999.60 ABO incompatibility reaction, unspecified


  • T80.92XA Unspecified transfusion reaction, initial encounter
  • T80.919A Hemolytic transfusion reaction, unspecified incompatibility, unspecified as acute or delayed, initial encounter
  • R50.84 Febrile nonhemolytic transfusion reaction
  • J95.84 Transfusion-related acute lung injury (TRALI)
  • T80.39XA Oth ABO incompat react due to tranfs of bld/bld prod, init
  • T80.49XA Oth Rh incompat reaction due to tranfs of bld/bld prod, init
  • T80.89XA Oth comp fol infusion, transfuse and theraputc inject, init


  • 82545002 Blood transfusion reaction (disorder)
  • 39778006 Hemolytic transfusion reaction (disorder)
  • 73301000 febrile transfusion reaction (disorder)
  • 389078002 Transfusion related acute lung injury (disorder)
  • 341009 ABO incompatibility reaction
  • 88924008 Rh incompatibility reaction (disorder)


  • Q: What is the risk of acquiring certain viral infections?
  • A: Hepatitis B: 1:300,000 transfused units; hepatitis C: 1:1,800,000 transfused units; HIV: 1:2,300,000 transfused units
  • Q: What is the risk of developing bacterial sepsis?
  • A: 1:1,000,000 red cell units; 1:13,000 to 100,000 platelet units
  • Q: Is directed donor blood safer?
  • A: No. There is no evidence that the infection risk is lower, and some studies suggest that the infection risk may be higher.
  • Q: Is it safe to give a transfusion to a patient with fever?
  • A: Yes. However, if the temperature rises during the transfusion or if symptoms such as chills or hypotension develop, the transfusion should be stopped and the patient evaluated for a transfusion reaction.


Kristin A. Shimano, MD

© Wolters Kluwer Health Lippincott Williams & Wilkins