Basics
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. ‚
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 Jka or Jkb (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 " “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
Diagnosis
History
- Acute hemolytic
- Fever/chills
- Abdominal or flank pain
- Pink or tea-colored urine
- Tachycardia
- Hypotension
- Oliguria
- FNHTR
- Fever, chills 1 " “6 hours after transfusion
- Urticarial
- Urticaria
- Flushing
- Pruritus
- Anaphylactic
- Urticaria
- Bronchospasm
- Hypotension
- Bacterial sepsis
- DHTR
- Fever
- Malaise
- Dark urine
- Jaundice
- Shock (rarely)
- Renal failure 2 " “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 " “30 days after transfusion
Diagnostic Tests & Interpretation
Lab
- Acute hemolytic
- Direct Coombs test: positive
- CBC: anemia
- Urinalysis: hemoglobinuria
- Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin split products: disseminated intravascular coagulation (DIC)
- FNHTR
- Direct Coombs test: negative or no change from pretransfusion
- Immediate Gram stain of the product
- Blood culture of the patient and product
- All results should be negative; a diagnosis of exclusion.
- Urticarial
- Anaphylactic
- IgA level in recipient. If undetectable, test for anti-IgA antibody (of the IgE class).
- Bacterial sepsis
- Immediate Gram stain and blood culture of the transfused product: result positive for bacteria
- DHTR
- CBC: anemia
- Bilirubin: elevated
- Indirect Coombs test (antibody screen): positive
- Direct Coombs test: positive (mixed field) if done early
- TRALI
- Leukocyte antibody testing in the implicated donor(s)
Imaging
- Chest radiograph: increased pulmonary vascular markings or infiltrates for hypervolemia (TACO) and TRALI
Treatment
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 products, especially for long-term transfused patients who have a high incidence of febrile transfusion reactions
- No evidence to support premedication with Tylenol or Benadryl 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 " “15 mL/kg) at appropriate rate, usually over 3 " “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.
Additional Therapies
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 " “24 hours
- TACO: diuretics (furosemide)
- TA-GVHD: no treatment, almost always fatal
Ongoing Care
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-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, delayed hemolytic transfusion reactions, 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.
Additional Reading
- Lindholm ‚ PF, Annen ‚ K, Ramsey ‚ G. Approaches to minimize infection risk in blood banking and transfusion practice. Infect Disord Drug Targets. 2011;11(1):45 " “56. ‚ [View Abstract]
- Slonim ‚ AD, Joseph ‚ JG, Turenne ‚ WM, et al. Blood transfusions in children: a multi-institutional analysis of practices and complications. Transfusion. 2008;48(1):73 " “80. ‚ [View Abstract]
- Tobian ‚ AA, King ‚ KE, Ness ‚ PM. Transfusion premedications: a growing practice not based on evidence. Transfusion. 2007;47(6):1089 " “1096.
- Vamvakas ‚ EC, Blajchman ‚ MA. Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention. Blood. 2009;113(15):3406 " “3417. ‚ [View Abstract]
Codes
ICD09
- 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
ICD10
- 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)
FAQ
- Q: What is the risk of acquiring certain viral infections?
- A: Hepatitis B: 1:300,000 transfused units; hepatitis C: 1:1,800,000 transfused units; HIV: 1:2,300,000 transfused units
- Q: What is the risk of developing bacterial sepsis?
- A: 1:1,000,000 red cell units; 1:13,000 " “100,000 platelet units
- Q: Is directed donor blood safer?
- A: No. There is no evidence that the infection risk is lower, and some studies suggest that the infection risk may be higher.
- Q: Is it safe to give a transfusion to a patient with fever?
- A: Yes. However, if the temperature rises during the transfusion or if symptoms such as chills or hypotension develop, the transfusion should be stopped and the patient evaluated for a transfusion reaction.