DESCRIPTION

• Any acute or subacute adverse reaction that develops as a consequence of the administration of blood components
• Can be mild, moderate, severe, and even life-threatening or fatal
• Types (segregated by timing) include the following:
  • Acute reactions (<24 hours): hemolytic, febrile, allergic, anaphylactic, septic, transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO)
  • Delayed reactions (>24 hours to 30 days post transfusion): delayed hemolytic, transfusion-associated graft-versus-host disease (TA-GVHD)
  • Late complications of transfusion: infection, alloimmunization, iron overload
• There are overlapping symptoms of these reactions.

EPIDEMIOLOGY

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

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.
• Febrile nonhemolytic transfusion reaction (FNHTR)
  • Administration of prestorage-leukodepleted blood products reduces the risk of FNHTR by 50%, 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
  • No conclusive evidence to support premedication with antihistamines
  • Administration of washed erythrocyte products (in patients with repeated or severe allergic reactions)
• Anaphylactic
  • If due to anti-IgA in an immunoglobuin A (IgA)-deficient recipient, provision of IgA-deficient products may be possible.
  • Administration of washed erythrocyte products
• Bacterial sepsis
  • Sterile technique in blood collection, storage, and administration; inspection of product before transfusion
  • Bacterial screening of platelet products before they are transfused
• Delayed hemolytic transfusion reaction (DHTR)
  • Appropriately performed antibody screen and crossmatch as pretransfusion testing
  • Check blood bank records for previous antibodies.
    • Once a patient has developed an antibody, the antibody must always be taken into consideration when selecting a blood product.
• TRALI
  • Permanent deferral of donors implicated in proven TRALI cases
• TACO
  • Administer appropriate volumes (typically 10 to 15 mL/kg of packed red blood cells [PRBCs], may be less in certain clinical situations such as splenic sequestration—5 mL/kg) at appropriate rate, usually >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.

PATHOPHYSIOLOGY

• Acute hemolytic transfusion reaction
  • Antigen–antibody interaction leads to complement activation on the surface of the transfused red blood cells (RBCs), resulting in acute intravascular hemolysis and vasomotor instability.
  • Usually ABO blood group incompatibility
  • Most commonly due to medical error
• FNHTR
  • Cytokines released by leukocytes in the product during storage
  • 40% of patients with one febrile reaction will have a subsequent one.
• Urticarial (allergic)
  • Immunoglobuin E (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 because they are kept in a warmer environment
• DHTR
  • Previously transfused patients who are sensitized to a minor blood group antigen, especially Jka or Jkb (Kidd antigen), develop an anamnestic response on subsequent exposure.
    • More common in patients with sickle cell disease
  • 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 human leukocyte antigen (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, which attack the bone marrow, skin, and gastrointestinal (GI) tract, where HLA class II antigens are expressed.
  • Can also occur if the donor and recipient are related and share HLA types

HISTORY

• Acute hemolytic (classic triad* frequently not seen)
  • Fever* or chills
  • Abdominal or flank pain*
  • Red-colored urine*
  • Tachycardia
  • Hypotension
  • Oliguria or anuria
  • Oozing from IV sites
• FNHTR
  • Fever 1 to 6 hours after transfusion
  • Chills
• Urticarial—usually within 4 hours after transfusion
  • Urticaria
  • Flushing
  • Pruritus
• Anaphylactic
  • Urticaria
  • Bronchospasm
  • Hypotension
• Bacterial sepsis
  • Fever
  • Chills
  • Hypotension
• DHTR
  • Fever
  • Malaise
  • Dark urine
  • Jaundice
  • Scleral icterus
  • Pallor
  • Shock (rarely)
  • Renal failure 2 to 10 days after transfusion
• TRALI—within 6 hours of transfusion
  • Fever
  • Chills
  • Acute dyspnea
  • Tachypnea
  • Rales
  • Decreased oxygenation
  • Hypotension
• TACO—within 6 hours of transfusion
  • Cough
  • Hypertension
  • Dyspnea
  • Rales
  • Cardiac arrhythmia
• TA-GVHD—symptoms within 4 to 30 days after transfusion
  • Fever
  • Rash
  • Diarrhea

DIAGNOSTIC TESTS & INTERPRETATION

GENERAL MEASURES

• Acute hemolytic
  • Stop transfusion immediately.
  • Supportive care: hydration with normal saline, diuretics to maintain urine output, and sometimes low dose dopamine
• FNHTR
  • Stop transfusion.
  • Antipyretics (acetaminophen)
  • Meperidine (Demerol®) for severe chills and rigors
  • May resume transfusion if the patient is stable and acute hemolytic transfusion reaction and bacterial sepsis are ruled out
• Urticarial
  • Stop transfusion.
  • Antihistamine (diphenhydramine)
  • Corticosteroids or epinephrine in severe reactions
  • Transfusion may be resumed if mild reaction and symptoms lessen.
• Anaphylactic
  • Epinephrine
  • IV fluids, vasopressors
  • Respiratory support
• Bacterial sepsis
  • Stop transfusion.
  • Fluids if hypotensive
  • Antibiotics to eradicate Staphylococcus and gram negatives including Yersinia species, especially for patients with iron overload
• DHTR
  • Depends on degree of hemolysis; if profound, management as an acute hemolytic reaction; if mild, no therapy may be needed
• TRALI
  • Cardiopulmonary support
  • Usually resolves in 12 to 24 hours
• TACO
  • Respiratory support
  • Diuretics (furosemide)
• TA-GVHD
  • No treatment; supportive care (very high mortality rate from bone marrow failure)

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
  • Avoid CMV infection by using CMV-negative products for in utero transfusions, for premature neonates, and for CMV-negative transplant candidates with CMV-negative donors.
  • Other individuals should receive CMV-safe (leukoreduced) products in utero.
• Other transfusion-transmissible infections
  • Epstein-Barr virus, human T-cell lymphotropic virus I (HTLV-I), human herpes virus, West Nile virus, parvovirus B19, Zika virus
  • Parasites: malaria, toxoplasmosis, Chagas disease, babesiosis, filariasis
• 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 the eligibility and organ procurement for solid organ transplantation.
• Iron overload
  • Long-term transfusion recipients (>10 to 20 transfusions) will accumulate iron as a by-product of erythrocyte breakdown.
  • Iron-chelating medications will enhance iron excretion but also have many side effects.

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