The role of platelets in arterial thrombosis and the rationale for blockade of platelet GPIIb/IIIa receptors as antithrombotic therapy.
Platelet aggregation plays a crucial role in ischaemic arterial thrombosis. Recent biochemical data indicate that the platelet glycoprotein (GP) IIb/IIIa receptor mediates platelet aggregation by binding fibrinogen, von Willebrand factor, or other ligands, that can span between platelets. New antiplatelet agents that block the binding sites on GPIIb/IIIa are efficacious in arterial thrombosis animal models and are now being evaluated in human disease. A mouse/human chimeric monoclonal antibody fragment (c7E3 Fab) and agents modelled after the arginine-glycine-aspartic acid (RGD) cell binding motif are in development. c7E3 Fab showed significant efficacy in reducing ischaemic complications after angioplasty in patients at high risk of such complications in the EPIC study, and thus has been approved for use in the U.S. and several European and Scandinavian countries. These new agents also hold considerable promise in the treatment of other thrombotic disorders, including unstable angina and myocardial infarction.
Coller
B S
BS
Department of Medicine, Mount Sinai Medical Center, New York, 10029-6574, USA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001158:Arteries; D001792:Blood Platelets / Q000502:physiology*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000209:etiology*; D014652:Vascular Diseases / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex