Severe autoimmune hemolytic anemia associated with IgM warm autoantibodies directed against determinants on or associated with glycophorin A

Background and objectives: Autoimmune hemolytic anemia (AIHA) is rarely caused by IgM warm autoantibodies, and is sometimes difficult to diagnose. We describe three patients with severe AIHA caused by IgM warm autoantibodies; in two of the three, the hemolysis was fatal. Materials and methods: Conventional hematologic and serologic procedures were used. Results: The IgM autoantibodies in all three cases were directed against determinants on or associated with glycophorin A (En^a, Wr^b, and Pr). The IgM autoantibodies had unusual serological characteristics, in that the agglutinins were detected or greatly enhanced only by the presence of albumin or a low pH, and/or the agglutinins reacted optimally at 20-30°C. Conclusions: IgM warm autoantibodies directed at determinants on or associated with glycophorin A appear to cause severe (often fatal) hemolytic anemia.