Transfusion reactions

Last updated: November 20, 2023

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Summarytoggle arrow icon

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.”

Overviewtoggle arrow icon

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) [2][3]
  • 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
  • IVIG therapy

Nonimmunological transfusion complications

Overview of nonimmunological transfusion complications
Complications Background Features Management
Transfusion-associated sepsis
Transfusion-associated circulatory overload (TACO)
Massive transfusion-related complications [4] 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

Acute transfusion reactionstoggle arrow icon

General principles [12]

  • 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
  • No extracutaneous features
Respiratory distress

Acute hemolytic transfusion reactiontoggle arrow icon


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

Frequency [2]

Pathophysiology [2]

Clinical features [2]

Diagnosis [2][4]

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 [17]

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

Febrile nonhemolytic transfusion reactiontoggle arrow icon


  • Frequency: 1 in 900 transfusions (more common in children) [2][3]
  • Pathophysiology

Clinical features

Diagnosis [2][4]

Management [2][4]

Premedication with antipyretics to prevent FNHTR is not supported by available evidence. [2][4]

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

Anaphylactic transfusion reactiontoggle arrow icon

See also “Anaphylaxis.”

Minor allergic transfusion reactiontoggle arrow icon

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

Pulmonary transfusion complicationstoggle arrow icon


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 [5]

Cardiac features (may be present)
  • Usually present
  • Sometimes present
Diagnostics [5] Laboratory studies
  • CBC: Nonspecific
  • BNP: Typically elevated
Improves with a trial of diuresis
  • No
  • Yes

Massive transfusion-associated complicationstoggle arrow icon

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). [4][22]

Septic transfusion reactiontoggle arrow icon

See also “Sepsis.”

Acute management checklist for acute transfusion reactionstoggle arrow icon

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 reactionstoggle arrow icon

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). [12]

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 [4]

Referencestoggle arrow icon

  1. Delaney M, Wendel S, Bercovitz RS, et al. Transfusion reactions: prevention, diagnosis, and treatment. The Lancet. 2016; 388 (10061): p.2825-2836.doi: 10.1016/s0140-6736(15)01313-6 . | Open in Read by QxMD
  2. The National Blood Authority’s Patient Blood Management Guideline: Module 1 – Critical Bleeding/Massive Transfusion. Updated: January 1, 2011. Accessed: February 17, 2021.
  3. Bolliger D, Görlinger K, Tanaka KA, Warner DS. Pathophysiology and Treatment of Coagulopathy in Massive Hemorrhage and Hemodilution. Anesthesiology. 2010; 113 (5): p.1205-1219.doi: 10.1097/aln.0b013e3181f22b5a . | Open in Read by QxMD
  4. Balvers K, Coppens M, van Dieren S, et al. Effects of a hospital-wide introduction of a massive transfusion protocol on blood product ratio and blood product waste. J Emerg Trauma Shock. 2015; 8 (4): p.199.doi: 10.4103/0974-2700.166597 . | Open in Read by QxMD
  5. Green AR. Postgraduate Haematology. John Wiley & Sons ; 2011
  6. Goel R, Tobian AAR, Shaz BH. Noninfectious transfusion-associated adverse events and their mitigation strategies. Blood. 2019; 133 (17): p.1831-1839.doi: 10.1182/blood-2018-10-833988 . | Open in Read by QxMD
  7. Hawkins J, Aster RH, Curtis BR. Post-Transfusion Purpura: Current Perspectives. Journal of Blood Medicine. 2019; Volume 10: p.405-415.doi: 10.2147/jbm.s189176 . | Open in Read by QxMD
  8. $Contributor Disclosures - Transfusion reactions. All of the relevant financial relationships listed for the following individuals have been mitigated: Jan Schlebes (medical editor, is a shareholder in Fresenius SE & Co KGaA). None of the other individuals in control of the content for this article reported relevant financial relationships with ineligible companies. For details, please review our full conflict of interest (COI) policy.
  9. Oakley FD, Woods M, Arnold S, Young PP. Transfusion reactions in pediatric compared with adult patients: a look at rate, reaction type, and associated products. Transfusion (Paris). 2014; 55 (3): p.563-570.doi: 10.1111/trf.12827 . | Open in Read by QxMD
  10. Semple JW, Rebetz J, Kapur R. Transfusion-associated circulatory overload and transfusion-related acute lung injury. Blood. 2019; 133 (17): p.1840-1853.doi: 10.1182/blood-2018-10-860809 . | Open in Read by QxMD
  11. Haass KA, Sapiano MRP, Savinkina A, Kuehnert MJ, Basavaraju SV. Transfusion-Transmitted Infections Reported to the National Healthcare Safety Network Hemovigilance Module. Transfus Med Rev. 2019; 33 (2): p.84-91.doi: 10.1016/j.tmrv.2019.01.001 . | Open in Read by QxMD
  12. Levy JH, Neal MD, Herman JH. Bacterial contamination of platelets for transfusion: strategies for prevention.. Crit Care. 2018; 22 (1): p.271.doi: 10.1186/s13054-018-2212-9 . | Open in Read by QxMD
  13. AABB: Regulatory for blood and blood components/Donor safety, testing, and labeling. . Accessed: January 3, 2021.
  14. Strobel E. Hemolytic Transfusion Reactions.. Transfus Med Hemother. 2008; 35 (5): p.346-353.doi: 10.1159/000154811 . | Open in Read by QxMD
  15. Parker V, Tormey CA. The Direct Antiglobulin Test: Indications, Interpretation, and Pitfalls. Arch Pathol Lab Med. 2017; 141 (2): p.305-310.doi: 10.5858/arpa.2015-0444-rs . | Open in Read by QxMD
  16. Bakdash S, Yazer MH. What every physician should know about transfusion reactions. Can Med Assoc J. 2007; 177 (2): p.141-147.doi: 10.1503/cmaj.061106 . | Open in Read by QxMD
  17. $Red Blood Cell Transfusion: a pocket guide for the clinician.
  18. Norfolk D. Handbook of transfusion medicine, 5th edition. United Kingdom Blood Services ; 2013
  19. Bux J, Sachs UJ. The pathogenesis of transfusion-related acute lung injury (TRALI).. Br J Haematol. 2007; 136 (6): p.788-99.doi: 10.1111/j.1365-2141.2007.06492.x . | Open in Read by QxMD
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  22. Vlaar APJ, Veelo DP. The First Steps in Understanding of Transfusion-Associated Circulatory Overload—We Are on a “Roll”. Crit Care Med. 2018; 46 (4): p.650-651.doi: 10.1097/ccm.0000000000002971 . | Open in Read by QxMD
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