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Transfusion Reaction, Pediatric

Basics

Description

- Acute hemolytic - Fever/chills - Abdominal or flank pain - Pink or tea-colored urine - Tachycardia - Hypotension - Oliguria

- Urticarial - Urticaria - Flushing - Pruritus

- TACO - Hypertension - Dyspnea - Rales - Cardiac arrhythmia

- TA-GVHD - Fever - Rash - Diarrhea - Cough 4 " “30 days after transfusion

- 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)

- DHTR - CBC: anemia - Bilirubin: elevated - Indirect Coombs test (antibody screen): positive - Direct Coombs test: positive (mixed field) if done early

- DHTR - Appropriately performed antibody screen and crossmatch as pretransfusion testing - Check blood bank records for previous antibodies.

- 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

- Bacterial sepsis - Stop transfusion. - Fluids if hypotensive - Antibiotics to eradicate Staphylococcus and Gram negatives including Yersinia species

  • 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 reactionAntigen " “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 incompatibilityMost commonly due to medical error
  • Febrile nonhemolytic transfusion reaction (FNHTR)Cytokines released by leukocytes in the product40% of patients with one febrile reaction will have a subsequent one.
  • Urticarial (allergic)IgE-mediatedRecipient allergic response to donor plasma proteins or other constituents of plasmaSporadic and donor dependent
  • AnaphylacticOverwhelming acute allergic reaction. Can be mediated by anti-IgA formed by a recipient who is IgA deficient and receives blood products containing IgA
  • Bacterial sepsisIntravascular 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.
  • TRALIAntileukocyte 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.
  • TACOCirculatory overload leading to heart failureAdministration of an excessive volume of a blood product or infusion at an excessive rate
  • TA-GVHDPatients 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 hemolyticFever/chillsAbdominal or flank painPink or tea-colored urineTachycardiaHypotensionOliguria
  • FNHTRFever, chills 1 " “6 hours after transfusion
  • UrticarialUrticariaFlushingPruritus
  • AnaphylacticUrticariaBronchospasmHypotension
  • Bacterial sepsis
  • DHTRFeverMalaiseDark urineJaundiceShock (rarely)Renal failure 2 " “10 days after transfusion
  • TRALIAcute dyspnea, tachypnea, rales, decreased oxygenation within 6 hours of transfusion
  • TACOHypertensionDyspneaRalesCardiac arrhythmia
  • TA-GVHDFeverRashDiarrheaCough 4 " “30 days after transfusion

Diagnostic Tests & Interpretation

Lab

  • Acute hemolyticDirect Coombs test: positiveCBC: anemiaUrinalysis: hemoglobinuriaProthrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin split products: disseminated intravascular coagulation (DIC)
  • FNHTRDirect Coombs test: negative or no change from pretransfusionImmediate Gram stain of the productBlood culture of the patient and productAll results should be negative; a diagnosis of exclusion.
  • Urticarial
  • AnaphylacticIgA level in recipient. If undetectable, test for anti-IgA antibody (of the IgE class).
  • Bacterial sepsisImmediate Gram stain and blood culture of the transfused product: result positive for bacteria
  • DHTRCBC: anemiaBilirubin: elevatedIndirect Coombs test (antibody screen): positiveDirect Coombs test: positive (mixed field) if done early
  • TRALILeukocyte 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 hemolyticProper labeling of blood specimens and products and adherence to procedures for correct identification of product and recipient will eliminate most acute hemolytic transfusion reactions.
  • FNHTRAdministration of leukodepleted products, especially for long-term transfused patients who have a high incidence of febrile transfusion reactionsNo evidence to support premedication with Tylenol or Benadryl to prevent FNHTR
  • UrticarialAdministration of washed erythrocyte products (in patients with repeated or severe allergic reactions)No conclusive evidence to support premedication with antihistamines
  • AnaphylacticIf due to anti-IgA in an IgA-deficient recipient, provision of IgA deficient products may be possible.
  • Bacterial sepsisSterile technique in blood collection, storage, and administration; inspection of product before transfusionBacterial screening of platelet products before they are transfused
  • DHTRAppropriately performed antibody screen and crossmatch as pretransfusion testingCheck blood bank records for previous antibodies.
  • TRALIDeferral of donors is implicated in proven TRALI cases.
  • TACOAdminister 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-GVHDPatients at risk (immunocompromised, neonates) must receive irradiated blood products.

Additional Therapies

General Measures

  • Acute hemolyticStop transfusion immediately.Supportive care with hydration, pressors, and diuretics to maintain circulation and urine output
  • FNHTRStop transfusion.Antipyretics (acetaminophen)Demerol for severe chills and rigorsMay resume transfusion if patient is stable and acute hemolytic transfusion reaction and bacterial sepsis are ruled out
  • UrticarialStop transfusion.Antihistamine (diphenhydramine)Steroids or epinephrine in severe reactionsTransfusion may be resumed if mild reaction
  • AnaphylacticEpinephrineIV fluids, pressorsRespiratory support
  • Bacterial sepsisStop transfusion.Fluids if hypotensiveAntibiotics to eradicate Staphylococcus and Gram negatives including Yersinia species
  • DHTRDepends on degree of hemolysis; if profound, management as acute hemolytic reaction. If mild, no therapy may be needed.
  • TRALISupportive 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 neonatesThese individuals should receive CMV-safe products.
  • Other transfusion-transmissible infectionsEpstein-Barr virus, syphilis, malaria, toxoplasmosis, human T-lymphotropic virus I (HTLV-I), Chagas disease, babesiosis, filariasis, West Nile virus, parvovirus B19
  • AlloimmunizationFormation 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 overloadLong-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.