We studied a female patient with cyclic fluctuation in platelet count following
splenectomy for
autoimmune thrombocytopenia. The cyclical fluctuation appeared to be in phase with her menstrual cycle and her platelet count was low during menses. Bone marrow examinations performed at the peak as well as the bottom of the platelet count showed normal or increased numbers of megakaryocytes. The patient's platelet count increased rapidly after intravenous
gamma-globulin (IVIgG)
therapy, suggesting that a failure of platelet production is unlikely to account for the cycle. Platelet-associated
IgM (PAIgM) was markedly elevated, whereas PAIgG was normal at any stage of the cycle.
MACE assay demonstrated that PAIgM contained
IgM anti-
glycoprotein (
GP) IIb-IIIa
autoantibodies. Comparison between
MACE assay using untreated and
EDTA-treated platelets at 37 degrees C demonstrated that the platelet-associated
IgM autoantibodies mainly recognized divalent
cation-dependent conformation(s) of GPIIb-IIIa. No
antibodies were, however, detected in her serum. The levels of
IgM anti-GPIIb-IIIa showed an inverse relationship with the platelet count. In spite of the marked increase in platelet count after IVIgG, however, the levels of
IgM anti-GPIIb-IIIa remained elevated. These findings suggest that platelet-associated
IgM anti-GPIIb-IIIa
autoantibodies are of pathogenic significance in this patient.