Description

• 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

Epidemiology

• 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

Pathophysiology

• 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 Jk^a or Jk^b (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.
• TRALI
  • 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
• TA-GVHD
  • 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

History

• Acute hemolytic
  • Fever/chills
  • Abdominal or flank pain
  • Pink or tea-colored urine
  • Tachycardia
  • Hypotension
  • Oliguria
• FNHTR
  • 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
• TRALI
  • Acute dyspnea, tachypnea, rales, decreased oxygenation within 6 hours of transfusion
• TACO
  • Hypertension
  • Dyspnea
  • Rales
  • Cardiac arrhythmia
• TA-GVHD
  • Fever
  • Rash
  • Diarrhea
  • Cough 4 to 30 days after transfusion

Diagnostic Tests and Interpretation

General Measures

• Acute hemolytic
  • Stop transfusion immediately.
  • Supportive care with hydration, pressors, and diuretics to maintain circulation and urine output
• FNHTR
  • 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.
• TRALI
  • 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.

Complications

• 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.

ICD-9

• 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

ICD-10

• 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

SNOMED

• 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)