Understanding thrombocytopenia and antigenicity with glycoprotein IIb-IIIainhibitors

Platelet glycoprotein (GP) IIb-IIIa receptor antagonists are being used wit h increasing frequency in the settings of percutaneous coronary interventio ns and acute ischemic syndromes. The development of thrombocytopenia after GP IIb-IIIa blockade has been observed to some extent with all parenteral G P IIb-IIIa inhibitors studied to date and could potentially limit their eff ectiveness. The incidence and severity of thrombocytopenia has varied in la rge clinical trials with GP IIb-IIIa inhibitors, presumably as a consequenc e of the different structural and pharmacokinetic characteristics of the ag ents, the dose administered and duration of use, repetition of exposure, an d the various drugs coadministered with these agents. Certain baseline char acteristics may be predictive. In most cases, severe thrombocytopenia assoc iated with the use of GP IIb-IIIa receptor antagonists was readily reversib le with platelet transfusion and was not usually associated with major clin ical sequelae. Although the exact mechanisms responsible for thrombocytopen ia after GP IIb-IIIa blockade are poorly understood, an immune mechanism is suggested in which the binding of the antagonist to GP IIb-IIIa receptors leads to the exposure of ligand-induced binding sites recognized by preexis ting or induced antibodies. Alternatively, the receptor-drug metabolite com plex itself may induce an immune response. All patients receiving parentera l GP IIb-IIIa inhibitors should be monitored within 24 hours of initiation of therapy for the development of thrombocytopenia. An algorithm for the de tection and management of thrombocytopenia after GP IIb-IIIa inhibitor ther apy is proposed.