Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a target glycoprotein in drug-induced thrombocytopenia

Drug-induced immune thrombocytopenia (DITP) is a serious complication of dr ug treatment. Previous studies demonstrated that most drug-dependent antibo dies (DDAbs) react with the platelet membrane glycoprotein (GP) complexes I Ib/IIIa and Ib/IX/V. We analyzed the sera from 5 patients who presented wit h DITP after intake of carbimazole. Notably, thrombocytopenia induced by ca rbimazole was relatively mild in comparison to patients with DITP induced b y quinidine. The sera reacted with platelets in an immunoassay on addition of the drug. In immunoprecipitation experiments with biotin-labeled platele ts and endothelial cells, reactivity with the platelet endothelial cell adh esion molecule-1 (PECAM-1, CD31) could be demonstrated, whereas neither GPI Ib/IIIa nor GPIb/IX was precipitated in the presence of the drug. These res ults could be confirmed by GP-specific immunoassay (MAIPA) using monoclonal antibodies (mabs) against PECAM-1. In addition, the binding of DDAbs could be abolished by preincubation with soluble recombinant PECAM-1. Carbimazol e-dependent antibodies showed similar reactivity with platelets carrying th e Leu(126) and Val(125) PECAM-1 isoforms, indicating that this polymorphic Structure, which is located in the first extracellular domain, is not respo nsible for the epitope formation, Binding studies with biotin-labeled mutan ts of PECAM-1 and analysis of sera with mabs against different epitopes on PECAM-1 in MAIPA assay suggested that carbimazole-dependent antibodies prom inently bound to the second immunoglobulin homology domain of the molecule. Analysis of 20 sera from patients with quinidine-induced thrombocytopenia by MAIPA assay revealed evidence that DDAbs against PECAM-1 are involved in addition to anti-GPIb/IX and anti-GPIIb/IIIa. We conclude that PECAM-1 is an important target GP in DITP. (Blood. 2000;96:1409-1414) (C) 2000 by The American Society of Hematology.