Transfusion medicine
Transfusion reactions
Allergic / anaphylactic


Topic Completed: 18 August 2020

Minor changes: 19 August 2020

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PubMed Search: Allergic and anaphylactic transfusion reaction

Louise Helander, M.B.B.S.
Kyle Annen, D.O.
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Cite this page: Helander L, Annen K. Allergic / anaphylactic. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/transfusionmedallergic.html. Accessed November 25th, 2020.
Definition / general
  • Allergic reactions are the most common type of transfusion reaction
  • Usually mild but can range from simple urticarial reactions to life threatening anaphylaxis
  • Symptoms generally start within minutes of transfusion onset but can occur up to 4 hours following transfusion
  • Incidence:
    • Mild reactions: 0.03 - 0.61% RBC transfusions; 0.3 - 6% platelet transfusions; 1 - 3% plasma transfusions
    • Anaphylaxis: 1/20,000 - 1/47,000 transfusions (Autoimmun Rev 2014;13:163)
  • Most commonly occur following platelet or plasma transfusions but can occur following any blood component transfusion
  • Leukoreduction does not reduce the incidence
Essential features
  • Nonhemolytic in nature
  • Allergic transfusion reactions are common and generally mild, presenting as urticaria (hives) and pruritus (itching)
  • For a mild allergic reaction, a transfusion can be paused, the patient given appropriate medication (e.g. diphenhydramine) and if symptoms resolve completely, the transfusion may continue with observation; this is the only transfusion reaction that does not require a complete stop of the transfusion with a workup
  • Anaphylaxis is rare; historically attributed to IgA deficiency
  • IgA deficient patients should have an appropriate workup and do not require washed products unless a documented severe reaction has occurred in the past
Terminology
  • BAT (basophil activation test)
  • ELISA (enzyme linked immunosorbent assay)
  • PAS (platelet additive solution)
  • RBC (red blood cell)
  • TACO (transfusion associated circulatory overload)
  • TRALI (transfusion associated acute lung injury)
Pathophysiology
  • Not well understood
  • Type I / immediate hypersensitivity reaction:
    • B cells produce IgE antibodies in response to allergens (plasma proteins); these antibodies bind causing basophil and mast cell activation and degranulation (Transfus Med Rev 2018;32:43)
  • Plasma protein deficiencies:
    • Congenital or acquired protein deficiencies (IgA, haptoglobin, C3 / C4): patients can form antibodies against absent plasma proteins
      • IgA deficiency (IgA < 0.05 mg/dL):
      • Congenital haptoglobin deficiency
    • Passive sensitization:
Symptoms
  • Fever is not a symptom of allergic or anaphylactic reactions
  • The earlier in the transfusion the reaction starts, generally the more severe it is
  • Mild allergic reactions:
    • Urticaria, flushing, pruritus, mild / localized angioedema (eyes, lips, throat fullness)
  • Severe / anaphylactic reactions:
    • Allergic symptoms plus hypotension, dyspnea with or without signs of airway obstruction (wheezing, stridor), angioedema, abdominal pain, vomiting, loss of consciousness, shock
  • References: Shaz: Transfusion Medicine and Hemostasis, 2nd Edition, 2013, Fung: AABB Technical Manual, 19th Edition, 2017
Screening
  • There is no effective screening method for blood donors
Blood donor screening
  • For patients with true IgA deficiency who require plasma transfusion, the American Rare Donor Program (a joint program of the AABB and American Red Cross) may be able to provide a source (Transfus Med Hemother 2014;41:342)
  • IgA deficient plasma is very rare
Laboratory
  • Basophil activation test (BAT):
    • Basophil activation assessed using flow cytometry
    • May be useful in the diagnosis of allergic transfusion reactions but not commonly performed
  • IgA deficiency evaluation:
    • Immunoglobulin serum concentrations (IgM, IgG, IgA)
    • If severe IgA deficiency (< 0.05 mg/dL, typical adult normal range: 70 - 400 mg/dL depending on laboratory assay), perform anti-IgA antibody ELISA
    • Evaluation in children should occur after 6 months of age; in children younger than 4 years, the diagnosis is considered preliminary as levels may normalize into adolescence (Autoimmun Rev 2014;13:163)
Case reports
Treatment
  • Urticarial reaction (only):
    • Stop the transfusion
    • Administer antihistamine
    • Symptom resolution: restart the transfusion, no laboratory work up required
    • No symptom resolution: discontinue the transfusion, provide supportive care, report reaction to transfusion service
  • All other reactions:
Prevention
  • Prophylactic premedication is not recommended in patients with no history of allergic reaction
  • History of allergic reactions:
    • Premedication with antihistamines, H2 receptor antagonists or corticosteroids may be helpful depending on previous reaction severity
  • Patients with history of severe reactions (Blood 2019;133:1831):
    • Washed products (pRBCs, platelets) to remove donor plasma may be indicated
    • Platelets in platelet additive solution (PAS) may eliminate reactions with better posttransfusion platelet increases than washed platelets
    • Solvent detergent treated plasma
  • IgA deficient patients:
    • Majority do not require washed or modified products; trial with unmodified products first
    • If a history of anaphylactic reactions to transfusion, washed pRBCs and platelets, PAS platelets and IgA deficient plasma (rare donor program) may be indicated
Sample assessment & plan
  • Example 1: IgA deficiency evaluation
    • Assessment: Jane Smith is a 36 year old woman with a history of IgA deficiency. Laboratory review shows low IgA (< 10 mg/dL; normal adult range: 70 - 400 mg/dL) and anti-IgA is negative. The patient has no history of allergic or anaphylactic transfusion reactions; however, transfusion history is not available (patient required 2 units of pBRC for postpartum bleeding at an outside hospital in 2013). The patient is being evaluated for elective cholecystectomy.
    • Plan: If required, we will issue unmodified blood products
      • Although the patient has low IgA levels, the anti-IgA is negative
      • No history of allergic reaction during prior transfusions in 2013
      • Cholecystectomy has a low risk of bleeding complications
  • Example 2: allergic transfusion reaction
    • Assessment: Patient is a 17 year old boy with Hodgkin lymphoma and thrombocytopenia secondary to chemotherapy. The patient developed a rash across the chest and left upper arm with pruritus approximately 20 minutes into a transfusion of platelets which were irradiated and leukocyte reduced. The patient had received approximately 53 mL of platelets at the time of the reaction. The patient did not have any signs of respiratory distress and vital signs were stable. The transfusion was discontinued and the patient was given diphenhydramine, after which all symptoms resolved. Blood bank workup showed no clerical errors. There is no evidence of hemolysis and the DAT was negative on both pre and posttransfusion samples.
    • Plan: No evidence of hemolysis. This is categorized as a mild transfusion reaction.
      • Premedication is suggested only if the patient has additional allergic reactions; evidence has found that there is limited benefit to premedication for mild transfusion reactions
      • Patient may receive additional transfusions as needed; if another mild reaction occurs, the transfusion may be paused and the patient can be given antihistamines; if all symptoms resolve within 20 minutes, the transfusion may be resumed
      • For any transfusion reaction with fever, respiratory distress, hypertension or hypotension, the transfusion must be discontinued and reported to the blood bank immediately
Differential diagnosis
Additional references
Board review style question #1
A healthy, 65 year old woman is admitted to the hospital for total hip arthroplasty. During the procedure, her vital signs are within normal limits but she experiences significant bleeding. In the recovery room, she is found to have a hemoglobin of 6.2 g/dL (normal female reference range: 12 - 16 g/dL) and complains of shortness of breath. A RBC transfusion is ordered. Halfway through transfusion, the patient begins to complain of itching with red raised wheals on her arms and chest. She remains short of breath, although her other vital signs are stable. Which of the following adverse reactions to transfusion has the patient most likely experienced?

  1. Allergic transfusion reaction
  2. Anaphylaxis
  3. Bacterial contamination of the donor unit
  4. Transfusion related acute lung injury (TRALI)
  5. Transfusion associated circulatory overload (TACO)
Board review answer #1
A. Allergic transfusion reaction. While allergic transfusion reactions are most commonly seen with platelets, they can occur with any blood product. The patient displays a classic urticarial reaction, which is frequently accompanied by pruritus. She remains short of breath as her anemia has not yet been resolved. Her symptoms are not severe enough at this point to be considered an anaphylactic reaction. She is afebrile, making TRALI or bacterial contamination unlikely. She only received part of a unit of pRBCs following a surgery, making it unlikely that TACO is responsible. TACO also does not present with an urticarial reaction.

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Board review style question #2
A 42 year old man, status post bone marrow transplant, arrives at the hospital infusion clinic for continued transfusion support. Following labs, he is found to be thrombocytopenic and a platelet unit is ordered. 10 minutes into the platelet transfusion, large red wheals appear across the patient's chest. His vital signs are stable and he reports no shortness of breath. The nurse stops the transfusion and administers 50 mg of diphenhydramine PO. His symptoms resolve. With regard to the remaining platelet volume, the nurse should

  1. Discard the remainder of the unit and notify the transfusion service so they may initiate a transfusion reaction workup
  2. Discontinue the transfusion and return the unit to the transfusion service for transfusion reaction workup
  3. Restart the transfusion, monitoring the patient for the return of symptoms
  4. Restart the transfusion without further patient monitoring
Board review answer #2
C. Restart the transfusion, monitoring the patient for return of symptoms. A mild urticarial allergic reaction that resolves with antihistamines is the only scenario in which a transfusion can be restarted and in which the transfusion service does not need to be notified that a reaction has occurred. If the patient again develops urticaria following restarting of the unit, the transfusion must be permanently discontinued and the unit returned to the blood bank for further investigation.

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