title: GPIIb/IIIa inhibitor-induced dethrombosis.
abstract: GPIIb/IIIa inhibitors have demonstrated clinical benefit in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. As opposed to the well documented prevention of platelet aggregation by GPIIb/IIIa inhibitors, we here discuss the less well appreciated reversal of platelet aggregation by, and dethrombotic effects of, GPIIb/IIIa inhibitors. In vivo evidence for GPIIb/IIIa inhibitor-induced dethrombosis includes animal models of arterial thrombosis and human studies (both observational and randomized clinical trials) in the setting of acute myocardial infarction. These human studies demonstrated increased coronary perfusion prior to percutaneous coronary intervention in patients receiving GPIIb/IIIa inhibitors as compared to those patients receiving placebo. Mechanisms of GPIIb/IIIa inhibitor-induced dethrombosis include alterations in thrombus size and structure, reduced capacity for subsequent thrombus growth, inhibition of soluble CD40L release from platelets, and a direct platelet disaggregatory effect that parallels fibrinogen's interactions with GPIIb/IIIa. In summary, mechanistic studies, animal models, human observational studies and randomized clinical trials all strongly suggest that GPIIb/IIIa inhibitors have a direct dethrombotic effect in addition to their well-described preventative effects on platelet aggregation.
authors.affiliation: Center for Platelet Function Studies, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. mark.furman@umassmed.edu
authors.forename: Mark I
authors.initials: MI
authors.lastname: Furman
authors.forename: A L
authors.initials: AL
authors.lastname: Frelinger
authors.forename: Alan D
authors.initials: AD
authors.lastname: Michelson
mesh_terms: D000818:Animals; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000502:physiology; D016032:Randomized Controlled Trials as Topic
chemical_list: D005343:Fibrinolytic Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex