A nine-year-old boy had typical clinical, hematologic and blood group serologic findings of autoimmune hemolytic anemia except for one important exception; with most commercially available broad spectrum anti-human sera the direct antiglobulin tests were negative. With reagents prepared in the laboratory which were found to be relatively less potent in and anti-IgG and IgM activity but which utilize a short period of incubation after mixing with the washed cells, the tests were all clearly positive. If incubation were employed with the commercial reagents, the tests were positive. Further studies showed that the patient's cells were coated exclusively with IgA and that a commercial reagent, although potent in anti-IgG and anti-IgM, was relatively deficient in anti-IgA. It is proposed that incubation compensates for the latter and is cautioned that incubation, with reagents potent in anti-IgG, could lead to false negative reactions with weakly IgG sensitized cells due to antibody surplus prozones of inhibition. This case illustrates that the rare instances of "Coombs negative immune hemolytic anemias" may be based on mechanisms such as those reported here and, that to be ideal, a broad spectrum anti-human serum should have balanced anti-immunoglobulin activities in relation to its incubation time.
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