A transfusion medicine physician in Northern California is trying to establish a practice at her academic medical center regarding patients who are known to be IgA-deficient, but who are previously/historically known to lack anti-IgA antibody. According to her research, both the AABB's book on Transfusion Reactions (ed. Popovsky, 2001 pg 113) and the American Rare Donor Program in Philadelphia recommend that patients with no detectable anti-IgA can be transfused with standard blood products. Neither source gives any recommendation for future anti-IgA testing of these individuals. The inquiring physician would like to ask how others are handling transfusions to their known IgA-deficient patients who previously have had no evidence of IgA antibodies on testing. Should patients be retested for IgA antibodies at some point, such as before additional transfusion episodes? She adds that at her hospital they have seen several IgA-deficient patients recently, and this question surfaced when they reviewed their policies and realized that they did not address this particular circumstance.

(Editor's note: Colleagues may find our earlier discussion germane to this new dialogue)

The following responses were received.

ADDENDA May 23, 2003

1. A colleague at another major academic center in Northern California is of the opinion that the recommendation by both AABB and American Red Cross that patients with no detectable anti-IgA antibodies can be transfused with standard blood products is very well founded for the following reasons (verbatim):

1. "High-titered (>1:1000) class-specific anti-IgA antibodies, occurring only in patients with no serum IgA, are responsible for causing typical anaphylactic transfusion reactions to infusion of small amounts of blood products containing IgA (N Engl J Med 280:1073-4, 1969).
2. Although IgA deficiency (serum IgA less than 0.1% of the normal) is a heterogeneous phenotype, a remarkable dichotomy has been consistently observed by all investigators in this field. A small but defined subgroup of patients who have no serum IgA detected by any method, in fact lack expression of IgA (aIgA) and produce class-specific antibodies to IgA, which react with both subclasses IgA1 and IgA2. Thus, conceptually aIgA is an immunogenetically determined phenotype in which synthesis of IgA is completely blocked despite the presence of IgA1 and IgA2 heavy chain genes present on chromosome 14 (Clin Exp Immunol, 60:661-4, 1985). Upon exposure to IgA as a foreign protein, persons with the aIgA phenotype readily produce class-specific anti-IgA.
3. Many of the aIgA patients have no history of transfusion or exposure to blood products but they are at the risk of suffering anaphylactic transfusion reactions when exposed to small amounts of blood or blood products containing human IgA. Exposure to maternal IgA in breast milk may be a common mode of immunization in early fetal life; however, an uncommon exposure to maternal IgA in intrauterine life may also induce class-specific anti-IgA (Nature, 225:275-6,1970).
4. While a majority of IgA deficiency (dIgA) patients do not express normal amounts of IgA in their serum, they have low levels of IgA (progressively detectable by more sensitive techniques) and do not produce typical class-specific antibodies to IgA1 and IgA2 subclasses. Such dIgA patients may not be at risk of anaphylactic transfusion reactions despite repeated transfusions or exposures to blood products containing IgA. Several of the patients with common variable immune deficiencies are treated with pooled immune serum globulins without immunization to IgA class of proteins. Such patients do not get repeated screening for anti-IgA antibodies if they are found to be negative for anti-IgA after start of gamma globulin therapy.
5. The AABB and ARC recommendation is in conformity with our work carried out in collaboration with Dr. Herbert Perkins (J Lab Clin Med, 85:838-42, 1975). In screening 73,569 voluntary blood donors by Ouchterlony gel diffusion analysis we found 113 donors to have no detectable IgA. Remarkably, 13 of the aIgA donors had class-specific anti-IgA. Passive infusion of these class-specific anti-IgA in transfusion recipients apparently did not provoke any anaphylactic reactions. Of the remaining 100 specimens without class-specific anti-IgA antibodies, 71 unselected sera were sent to Dr. Derek Naylor in Toronto for testing by the most sensitive radioimmunoassay. He reported that 58/71 had varying low levels of IgA, consistent with his published report (Vox Sang, 47:60-67, 1984).
6. The anaphylactic reactions are mediated by IgG (Lancet ii:312-5, 1968) and not IgE anti-IgA (Transfusion, 21:38-44, 1981).

I hope this analysis of dIgA not producing class-specific anti-IgA will help our colleague to make an educated decision regarding anti-IgA testing."

2. A colleague in Edmonton, Alberta reports that her laboratory recently evaluated an Rh positive pregnant patient who had IgA deficiency (<0.05 mg/dL) but no detectable anti-IgA. The patient was scheduled for an elective C-section in a remote community hospital. The hospital had one unit of IgA-deficient plasma on hand during the patient's C-section. Fortunately, the patient did not need any transfusions, but if she had needed one, the inquiring Canadian wants to know if other colleagues would have had IgA-deficient blood products on hand. [Webmaster's note: If colleagues are of the opinion that this patient should have had IgA-deficient plasma available, do you also agree that having a single unit of FFP was NOT a sufficient dose in the event the patient's C-section was complicated by massive bleeding?]. In this case, except for the single unit of IgA-deficient plasma, the responding colleague's service recommendation to the patient's physician was to administer standard (not IgA-deficient) blood products, if required. In addition, because the patient was Rh positive they did not worry about administering Rh immunoprophylaxis. However, had the patient been Rh negative, would colleagues have been concerned about administering RHIG? Finally, in the event this patient had been transfused with standard blood products, the Canadian colleague reports that their recommendation to the patient's physician would have been to retest the patient for anti-IgA at 6 weeks to 3 months post-transfusion. The Canadian colleague wants to know what others recommend regarding the above situations.

Editor's second note: The response from the Northern California colleague seems to address many of the concerns of the Canadian colleague in reply #2, as well as those of the transfusion medicine physician who submitted this issue.

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator