Hemagglutination assays for the diagnosis and prevention of IgA anaphylactic transfusion reactions

Abstract

Passive hemagglutination assays (PHA) may be used to detect IgA antibodies to confirm clinical diagnoses of suspected IgA anaphylactic transfusion reactions. Passive hemagglutination inhibition assays (PHIA) may be used to identify IgA-deficient blood donors whose plasma- containing components are transfused to prevent anaphylactic transfusion reactions in prospective recipients at risk because of the presence of IgA antibodies. Using a standard PHA, we detected class- specific anti-IgA in 76.3% of 80 IgA-deficient patients with a history of an anaphylactic transfusion reaction, and in 21.7% of 97 asymptomatic IgA-deficient blood donors or their IgA-deficient family members. Using PHIA, we confirmed IgA deficiency (< 0.05 mg/dL) for the donors of 525 plasma-containing blood components that were transfused without acute clinical reactions to 48 IgA-deficient recipients with anti-IgA and/or a history of an anaphylactic transfusion reaction. The frequency of IgA-deficiency with class-specific anti-IgA among 32,376 random blood donors was 0.08% (1/1,200). The combined use of PHA for detecting anti-IgA and PHIA for measuring IgA concentration provides an effective and safe strategy for the diagnosis and prevention of IgA anaphylactic transfusion reactions. However, PHA for anti-IgA lacks specificity for identifying persons who are truly at risk for significant anaphylactic transfusion reactions. The consequence is an overdiagnosis of IgA anaphylactic transfusion reactions and an overestimation of the number of persons at risk for IgA anaphylactic transfusion reactions because of the detection of an IgA antibody in their serum.

Recombinant human immunoglobulin (Ig)A1 and IgA2 anti‐D used for detection of IgA deficiency and anti‐IgA

“…Almost all severe anti-IgA anaphylactic reactions, however, have been caused by class-specific anti-IgA, that is, antibodies directed against epitopes found on both IgA1 and IgA2. In 80 IgA-deficient patients (<500 ng/mL) with a history of anaphylactic transfusion reaction, Sandler and coworkers 31 detected 63 persons with anti-IgA. Of these, 62 were class-and subclass-specific anti-IgA and 1 was allotypespecific.…”

The entity of immunoglobulin A–related anaphylactic transfusion reactions is not evidence based

“…Since this original publication in 1968, more than 40 additional case reports of IgA-related anaphylactic transfusion reactions have been published in peer-reviewed journals. [2][3][4][5] Nearly all of these reports define a transfusion reaction to be anti-IgA related if the patient's plasma agglutinated IgA myeloma-coated reagent RBCs in a direct hemagglutination assay. During the 46 years since publication of this initial report, clinicians have accepted IgA-related anaphylactic transfusion reaction as a valid diagnosis and tested patients for IgA and anti-IgA if they experienced a serious allergic transfusion reaction.…”

“…Transfusing physicians have requested IgAdeficient blood components for patients with severe allergic reactions and IgA deficiency or patients that they consider to be at higher risk of an anaphylactic reaction due to IgA deficiency with or without anti-IgA. [2][3][4][5][6][7][8] Despite the limitations of the laboratory tests and the inability to convincingly establish a diagnosis or confirm the pathogenicity of the detected anti-IgA, this approach often invokes misguided transfusion restrictions and unnecessary reliance on rare IgA-deficient blood components. Nevertheless, blood services worldwide have established registries of IgA-deficient donors to meet the demand for IgA-deficient blood components.…”

How I manage patients suspected of having had an IgA anaphylactic transfusion reaction

“…When the same anti-IgA assay that is used to diagnose reactions in patients was used in a program that screened 32,376 healthy blood donors for a registry of IgA-deficient donors, 1 in 1200 donors was found to be IgA-deficient (<0.05 mg/dL) with anti-IgA. 3 This number of random healthy persons who fulfill the laboratory criteria that are used conventionally to confirm a clinical diagnosis of an IgA-related transfusion reaction greatly exceeds the observed incidence of anaphylactic reactions in patients receiving transfusions.…”