Using age-fractionated erythrocytes, warm autoantibodies can be classified into two distinct categories, depending on their reactivity with reticulocyte-enriched (younger) or reticulocyte-poor (older) red cell fractions. The strength of the direct antiglobulin test (DAT) on the age-fractionated red cells of 24 patients indicated that 19 (79%) had an IgG warm autoantibody that reacted preferentially with older red blood cells. In 7 of these 19 patients (37%), the DAT was negative using reticulocyte-enriched red cell fractions. We have termed this preferential reactivity of warm autoantibodies with older red cells as type I. Five of the 24 patients studied (21%) had an IgG warm autoantibody that demonstrated no preference for young or older red cells. We have termed this pattern of warm autoantibody reactivity as type II. All 5 patients having type II warm autoantibodies had severe anemia. In contrast, 6 of 19 patients having type I warm autoantibody did not have clinical evidence of anemia when tested, and 11 of the 19 had only slight to moderate anemia. Additionally, our results using type I warm autoantibody raise questions regarding the blood group specificity of warm autoantibodies. The antigen recognized by type I warm autoantibody may be a cryptantigen. Rh specificity or relative Rh specificity, often associated with warm autoantibodies, may simply be a coincidental finding.

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