Glycoprotein IIb/IIIa antagonists: Potential induction and detection of drug-dependent antiplatelet antibodies, , ,

Development of acute, severe thrombocytopenia has been reported in several patients treated with a chimeric monoclonal antibody fragment to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) complex. However, the propensity of oral GPIIb/IIIa antagonists to induce antibody-mediated thrombocytopenia or platelet dysfunction with chronic exposure is unknown. There is evidence to suggest that a small percentage of otherwise healthy individuals have preexisting serum antibodies to conformation-dependent epitopes in the GPIIb/IIIa complex that are induced by certain members of this class of compounds that function as mixed agonists/antagonists. Additional studies are needed to identify the epitopes recognized by these antibodies and the requirement for the drug or a drug-metabolite to be present for antibody binding and detection. Detailed immunologic studies of antibodies from patients in whom immune thrombocytopenia develops after receiving oral GPIIb/IIIa antagonists may also provide insight into the mechanism by which activated platelets are normally cleared from the circulation. (Am Heart J 1998;135: S152-S159.)