IgA Deficiency
Severe IgA deficiency occurs in approximately 1 in 900 blood donors in the United States and United Kingdom. Approximately 20 to 30% of IgA deficient individuals, who are otherwise healthy, form anti-IgA antibodies, while approximately 80% of IgA deficient individuals with autoimmune disease form anti-IgA antibodies. Anti-IgA is usually IgG but may be IgM or IgE. Anti-IgA can have broad or limited specificity. When anti-IgA antibody binds to IgA in transfused plasma, complement is activated and severe anaphylaxis can occur.
Since 1968, patients with IgA deficiency and anti-IgA antibodies have been thought to be at increased risk of having an anaphylactic transfusion reaction following exposure to blood components containing IgA. A Commentary in the January 2015 issue of Transfusion questions this association and concludes that the entity of IgA-related anaphylactic transfusion reaction has not been established by evidence-based medicine (S.G. Sandler et al. Transfusion 2015;55:199-204).
Approximately 1 in 1200 individuals is IgA deficient and has detectable anti-IgA antibody. This is a much higher frequency than the incidence of anaphylactic transfusion reactions which is approximately 1 per 50,000 RBC transfusions. Therefore, not all individuals with IgA deficiency and anti-IgA, who are transfused, experience anaphylactic reactions.
The American Red Cross National Reference Laboratory provided some of the first evidence that anti-IgA was not the cause of the majority of anaphylactic transfusion reactions. Only 61 of 359 (17%) patients who experienced an anaphylactic transfusion reaction were IgA deficient with coexisting anti-IgA. (Sandler et al. Blood 1994;84:2031-5). More recent, hemovigilance data from other countries has documented that only 3 of 229 patients with anaphylactic or severe allergic reactions had IgA deficiency with anti-IgA. From 2008 through 2012, 12 cases of transfusion related fatal anaphylaxis cases were reported to the Food and Drug Administration (FDA). IgA deficiency was ruled out in 11 of the cases. IgA levels were not measured in the remaining case.
Transfusion of blood components from donors, who were subsequently identified to be IgA deficient with anti-IgA, to recipients with normal IgA levels does not cause anaphylaxis (Winters JL et al. Transfusion 2004;44:382-5).
This controversy creates a dilemma for the transfusion service regarding management of patients with a history of a severe allergic or anaphylactic transfusion reaction and/or laboratory evidence of IgA deficiency with or without anti-IgA antibodies. In my opinion, it remains prudent to err on the safe side.
Patients with severe allergic reactions after a transfusion should have an IgA level measured on a pretransfusion sample. The presence of IgA eliminates IgA deficiency as the cause of anaphylaxis and conventional transfusion therapy can be recommended. If IgA is not detected, testing for anti-IgA antibodies should be pursued. Patients with IgA deficiency and anti-IgA antibodies need to receive blood components which lack IgA. Plasma must be obtained from IgA-deficient donors. Red blood cells and platelets must be washed to remove as much plasma as possible.
Anaphylactic reactions have been seen in some IgA-deficient patients without detectable anti-IgA antibody. These patients should be carefully monitored for severe allergic reactions, but it may not be necessary to restrict them to washed or IgA-deficient products without a carefully monitored trial of unmodified blood products.
