The most common initial clinical manifestation of a hemolytic transfusion reaction is:

Summary

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.”

Overview

Immunological transfusion reactions

Nonimmunological transfusion complications

Acute transfusion reactions

Acute hemolytic transfusion reaction

Description

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

Pathophysiology [1]

• ABO incompatibility
• Non-ABO-related
  • Immune-mediated: the destruction of donor RBCs by recipient alloantibodies to non-ABO RBC antigens
  • Nonimmune-mediated: RBC destruction resulting from mechanical, thermal, or osmolar injuries

Clinical features [1]

• Rapid onset during transfusion (because of preformed antibodies) or up to 24 hours after the transfusion
• Clinical presentation ranges from asymptomatic to severe.
• Symptoms include: [12]
  • Fever, chills, nausea, flushing
  • Hypotension, tachycardia
  • Flank pain or chest pain
  • Dyspnea, tachypnea
  • Hemoglobinuria (due to intravascular hemolysis)
  • Jaundice (due to intravascular hemolysis)
  • Pruritus, urticaria
  • Burning pain at the IV site
  • Patients in a coma or under general anesthesia may present with oozing from wounds or puncture sites.
• Sequelae include:

AHTR is mainly a clinical diagnosis.

Confirmatory testing

Additional laboratory testing

AHTR is a medical emergency.

Stop the transfusion immediately if AHTR is suspected!

Febrile nonhemolytic transfusion reaction

Anaphylactic transfusion reaction

See also “Anaphylaxis.”

• Frequency: 1 in 30,000 transfusions [1]
• Pathophysiology
  • Type I hypersensitivity reaction in which preformed IgE antibodies on the surface of mast cells bind to donor plasma proteins (commonly donor IgA in recipients with IgA deficiency), leading to mast cell degranulation
  • Individuals with IgA deficiency should receive IgA-depleted blood products.
• Clinical features: Sudden onset during or up to 3 hours after the transfusion
  • Shock, hypotension, wheezing, respiratory distress
  • Skin reactions (e.g., pruritus, urticaria)
• Diagnosis [1]
  • Clinical diagnosis established according to diagnostic criteria for anaphylaxis
  • If the diagnosis is in doubt, consider workup for AHTR, TRALI, and septic transfusion reaction as the presenting features (e.g., hypotension, dyspnea) may be similar.
  • Consider testing the transfusion recipient for serum IgA levels and anti-IgA antibodies.
• Management [1]
• Prevention: in patients with a previous history of anaphylactic transfusion reaction [1]
  • Use washed blood products (platelets, RBCs) and solvent detergent plasma.
  • Use IgA-deficient blood products for patients with IgA deficiency.
  • The use of prophylactic antihistamines and/or steroids is commonly practiced but lacks supportive evidence. [3][16]

Minor allergic transfusion reaction

Pulmonary transfusion complications

Approach

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)

• Frequency: 1 in 60,000 transfusions [1][3]
• Pathophysiology [4]
• Differential diagnosis also includes: ARDS, AHTR, septic transfusion reaction, and anaphylactic transfusion reaction
• Management: Provide aggressive supportive care. [4][19]
• Prognosis
  • Mortality: 10–20% [15]
  • With appropriate support, TRALI typically resolves within 1–3 days of ceasing the transfusion. [16]

Distinguishing TRALI from TACO

Massive transfusion-associated complications

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]

• Hypocalcemia [3]
  • Resulting from the binding of ionized calcium by citrate (an anticoagulant added to RBC, platelet, FFP, and whole blood transfusion units)
  • Managed with monitoring of ionized calcium and calcium repletion
• Hyperkalemia [3]
  • 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.
  • Managed with monitoring of serum potassium and treatment as needed (see “Therapeutic approach to hyperkalemia”)
• Hypothermia [3]
  • Triggered by the rapid infusion of cold blood products
  • Can be prevented by using inline blood warming devices
• Coagulopathy [8]
  • Thought to be multifactorial, including dilution of platelets and clotting factors, hypothermia, and platelet dysfunction
  • Can be prevented by using a fixed ratio of blood products, e.g., a 1:1:1 of RBCs, FFP, and platelets [9]
  • See also “DIC.”

Septic transfusion reaction

See also “Sepsis.”

• Frequency [6]
  • Highest with platelet transfusions (approx. 1 in 10,000–50,000 units) [7]
  • Lower with other blood products (e.g., RBC: approx. 1 in 200,000 units)
• Microbiology [6][22]
  • Contaminated platelets: most commonly gram-positive organisms (e.g., Staphylococcus aureus, Streptococcusspp.)
  • Contaminated RBC: most commonly gram-negative organisms (e.g., Pseudomonasspp., Yersinia spp., Serratia spp.)
• Clinical features
  • Fever, hypotension, rigors, and other signs of SIRS
  • Usually manifests within 4 hours of transfusion
• Diagnosis [3]
  • Obtain bacterial cultures and Gram stains of the patient's blood and any recently transfused (within 4 hours) blood products.
  • Consider workup for AHTR and TRALI, as their presenting features (e.g., fever, hypotension, dyspnea) may be similar.
• Management [3]
  • Follow initial management steps for acute transfusion reactions.
  • Support hemodynamics with IV fluid resuscitation and vasopressors as needed.
  • Provide initial broad-spectrum empiric antibiotic therapy for sepsis, including antipseudomonal coverage if RBCs were given.

Acute management checklist for acute transfusion reactions

Initial management steps for acute transfusion reactions

• Stop the transfusion.
• Check patient and blood product IDs for compatibility.
• Maintain open IV access with normal saline.
• Draw blood for a repeat ABO typing and crossmatch.
• Perform a full ABCDE assessment and determine reaction severity.

All patients

• Provide symptomatic relief, e.g., oxygen, antihistamines, antipyretics.
• Identify the underlying cause of the reaction.
• Regularly reassess patients for signs of deterioration.
• Consider initial investigations: e.g., CBC, BMP, coagulation studies, hemolysis workup, urinalysis.
• Consider further investigations based on suspected underlying cause: e.g., Direct Coombs test, chest imaging, echocardiogram, BNP

Severe reactions

• Notify the blood bank and/or transfusion services.
• Consider hematology and ICU consult.
• Provide respiratory support and immediate hemodynamic support as needed.

Mild reactions

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

Delayed transfusion reactions

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)

• Frequency: 1 in 22,000 transfusions [1]
• Pathophysiology
• Clinical features [3]
  • Onset days or weeks after transfusion (due to the delay in the anamnestic response)
  • Most commonly asymptomatic
  • May cause:
    • Mild fever
    • Jaundice
    • Anemia
    • Chest, abdomen, or back pain
  • May be mistaken for vasoocclusive crises in patients with sickle cell disease (SCD)
• Diagnosis [1][3]
  • Positive DAT
  • CBC: to evaluate for anemia
  • Laboratory evidence of hemolysis
• Treatment [1][3]
  • Most cases are self-limited; and thus no acute therapy is usually required.
  • Additional RBC transfusions are preferably delayed (unless severe anemia) until the culprit alloantibodies are identified.
• Prevention [3]
  • Primary prevention in individuals requiring chronic transfusions (e.g., thalassemia, SCD): use of antigen-matched RBC units whenever feasible
  • Secondary prevention in individuals with identified alloantibodies: use of antigen-negative RBC units in future transfusions
  • See “Extended RBC phenotype matching.”

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

References

What is the most common hemolytic transfusion reaction?

What are the signs of hemolytic transfusion reaction?

What is the first indication of any transfusion reaction?

What is the most common cause of transfusion related hemolysis?