AUTOIMMUNE THROMBOCYTOPENIC PURPURA (AITP) AND ACQUIRED THROMBASTHENIA DUE TO AUTOANTIBODIES TO GP IIB-IIIA IN A PATIENT WITH AN UNUSUAL PLATELET MEMBRANE GLYCOPROTEIN COMPOSITION

The subject (E.B.) is a 63-year-old woman with autoimmune thrombocytop enic purpura (AITP) who was first examined some 6 years ago with sympt oms of epistaxis and gum bleeding, severe thrombocytopenia, and large platelets. Her serum tested positively with control platelets in the M AIPA assay performed using monoclonal antibodies (MoAb) to glycoprotei n (GP) IIIa (XIIF9, Y2/51), yet was negative in the presence of MoAbs to GP IIb (SZ22) or to the GP IIb-IIIa complex (AP2, P2). The patient' s platelets failed to aggregate with all agonists tested except for ri stocetin. IgG isolated from the patient's serum inhibited ADP-induced aggregation of control platelets, Unexpectedly, flow cytometry showed an altered expression of membrane glycoproteins on the patient's plate lets. Levels of GP Ib-IX were much higher than previously located by u s in platelets. In contrast, the expression of GP IIb-IIIa was about h alf that seen with control subjects, When Western blotting was perform ed, a striking finding was a strong band of 250 kDa recognized by a se ries of MoAbs to GP Ib alpha in addition to the band in the normal pos ition of GP Ib alpha. Finally, ADP-stimulated (E.B.) platelets failed to express activation-dependent epitopes on GP IIb-IIIa as recognized by PAC-1, AP6, or F26 and additionally gave a reduced P-selectin expre ssion after thrombin addition. In conclusion, we present a novel patie nt with a severely perturbed platelet function where an altered membra ne GP profile is associated with the presence of an autoantibody recog nizing a complex-dependent determinant on GP IIb-IIIa and inhibitory o f platelet aggregation. (C) 1998 Wiley-Liss, Inc.