Transfusion reactions

Last updated: May 27, 2022

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Blood component transfusions are usually safe and, given extensive screening and pretransfusion testing, serious adverse events are uncommon. When acute reactions occur they are typically mild, with the most common reactions including fever and rash. Rarely, more severe reactions can occur, causing respiratory distress, hemolysis, or shock. As there is significant overlap between the manifestations of mild transfusion reactions and the early stages of severe transfusion reactions, the first step is to stop the blood transfusion while assessment is performed. For minor transfusion reactions, it may be possible to restart the transfusion at a slower rate once more serious diagnoses have been excluded. Patients may also experience delayed transfusion reactions days to weeks after a transfusion. Delayed transfusion reactions typically have a more insidious presentation than acute reactions, and identifying them requires a high degree of clinical suspicion.

See also “Transfusion.”

Immunological transfusion reactions

Overview of immunological transfusion reactions
Background Clinical features Management
Acute hemolytic transfusion reaction (AHTR)
Febrile nonhemolytic transfusion reaction (FNHTR)
  • Frequency: 1 in 900 transfusions (more common in children) [1][2]
  • Mechanism: Cytokines released from old or lysed donor WBCs provoke an inflammatory reaction in the recipient.
Anaphylactic transfusion reaction
Minor allergic transfusion reaction
Transfusion-related acute lung injury (TRALI)
Delayed hemolytic transfusion reaction (DHTR)
  • Onset: days or weeks after transfusion
  • Most commonly asymptomatic
  • Features may include mild fever, jaundice, signs of anemia
Post-transfusion purpura

Nonimmunological transfusion complications

Overview of nonimmunological transfusion complications
Complications Background Features Management
Transfusion-associated sepsis
Transfusion-associated circulatory overload (TACO)
Massive transfusion-related complications [3] Hypocalcemia
  • Resulting from the lysis of RBCs in stored blood units; the risk is higher with increased transfusion rate and/or volume and longer storage age.
  • Prevention: inline blood warming devices

General principles [11]

  • Acute transfusion reaction refers to an immune or nonimmune-mediated adverse reaction that occurs during or within 24 hours of the transfusion of blood products.
  • All patients should undergo a similar initial assessment and management that is focused on stabilization until the underlying diagnosis can be determined.
  • Definitive treatment can be provided once the underlying cause has been identified.

Suspect an acute transfusion reaction in any patient who develops a change in vital signs (e.g., fever, hypotension) or any other new symptom during or within 24 hours of blood product transfusion.

Initial management steps for acute transfusion reactions

Do not restart blood component transfusion before a severe transfusion reaction has been ruled out.

Severity assessment

If uncertain, treat the reaction as severe.

Initial investigations

Do not delay stabilization measures pending results of a diagnostic workup in patients with suspected severe transfusion reactions.

Diagnostic approach

Symptom-based diagnostic approach to acute transfusion reactions
Symptom Associated features Potential causes
  • No other concerning features
  • Nontransfusion-related febrile illness
  • No extracutaneous features
Respiratory distress


Acute hemolytic transfusion reaction (AHTR) is an adverse reaction to blood transfusion that occurs within the first 24 hours after transfusion.

Frequency [1]

Pathophysiology [1]

Clinical features [1]

Diagnosis [1][3]

AHTR is mainly a clinical diagnosis.

Confirmatory testing

Additional laboratory testing


AHTR is a medical emergency.

Stop the transfusion immediately if AHTR is suspected!

Prognosis [16]

  • Significant disease progression (e.g., requiring intensive care admission) in approx. 30% of cases.
  • Death occurs in 5–10% of cases.


  • Frequency: 1 in 900 transfusions (more common in children) [1][2]
  • Pathophysiology

Clinical features

Diagnosis [1][3]

  • Clinical diagnosis based on the following findings (both must be present):
    • Temperature increase to ≥ 38°C or an increase of ≥ 1°C from baseline during or shortly after transfusion
    • Exclusion of other potential causes of fever during or following transfusion (e.g., AHTR, TRALI, sepsis)
  • Diagnostic evaluation
    • Check patient and blood bag IDs for compatibility and send a patient blood sample for DAT to rule out AHTR.
    • Consider blood cultures to evaluate for sepsis if any of the following are present:
    • Consider chest imaging (e.g., CXR) to evaluate for TRALI in patients with hypoxemia or respiratory distress.

Management [1][3]

Premedication with antipyretics to prevent FNHTR is not supported by available evidence. [1][3]

If a patient receiving a transfusion develops a fever, repeat donor and patient blood typing and crossmatching to rule out ABO incompatibility.

See also “Anaphylaxis.”

Routine premedication with antihistamines and/or steroids is NOT indicated in patients with a previous history of minor allergic transfusion reactions.


TRALI and TACO are both characterized by respiratory distress, i.e., dyspnea and hypoxemia, that develops acutely either during or within hours of transfusion.

Transfusion-related acute lung injury (TRALI)

Transfusion-associated circulatory overload (TACO)

Distinguishing TRALI from TACO

Differentiating between transfusion-related acute lung injury and transfusion-associated circulatory overload

Distinguishing clinical features [4]

Cardiac features (may be present)
  • Usually present
  • Sometimes present
Diagnostics [4] Laboratory studies
  • CBC: Nonspecific
  • BNP: Typically elevated
Improves with a trial of diuresis
  • No
  • Yes

Massive transfusion-associated reactions occur following the transfusion of large amounts of RBC units (e.g., > 10 units in 24 hours or ≥ 50% of the patient's blood volume in 4 hours), usually for cases of massive blood loss (e.g., from trauma or surgery). [3][21]

See also “Sepsis.”

Initial management steps for acute transfusion reactions

All patients

Severe reactions

Mild reactions

  • Rule out early presentation of severe reactions.
  • If symptoms resolve, consider resumption of blood transfusion at a slower rate.

Delayed transfusion reaction refers to an immune-mediated adverse reaction that occurs > 24 hours after the transfusion of blood products (can be weeks to months later). [11]

Delayed hemolytic transfusion reaction (DHTR)

Posttransfusion purpura

Platelet transfusions may be administered to patients with life-threatening bleeding but are usually ineffective in increasing platelet counts in patients with posttransfusion purpura.

Transfusion-associated graft-versus-host disease [3]

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  12. AABB: Regulatory for blood and blood components/Donor safety, testing, and labeling. . Accessed: January 3, 2021.
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  17. Norfolk D. Handbook of transfusion medicine, 5th edition. United Kingdom Blood Services ; 2013
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