Antiplatelet drugs play a central role in the practice of cardiology and include aspirin, platelet ADP-receptor antagonists and platelet glycoprotein IIb/IIIa inhibitors.
PLATELET BIOLOGY Platelet arterial wall adhesion, activation and aggregation play a pivotal role in the pathogenesis of arterial thrombosis and acute coronary syndromes. Hence agents with antiplatelet activity are amongst the most commonly prescribed drugs in the prevention and treatment of coronary disease. All antiplatelet agents interrupt one or more of the biological steps that lead from atherosclerotic plaque rupture to arterial thrombosis (Fig. 1). Rupture of an arterial plaque and disruption of the vascular endothelium expose a variety of factors that activate and recruit circulating platelets to aggregate. Some of these factors are released from the subendothelium (collagen, von Willebrand factor) while others are released by activated and degranulated platelets (thromboxane A2, adenosine diphosphate (ADP), serotonin). Intact vascular endothelium functions to prevent platelet activation and aggregation by releasing prostacyclin and nitric oxide. Vascular endothelial damage is an early and prominent feature of vascular disease that facilitates an unfavorable tilt in
the balance between antiaggregatory forces and proaggregatory forces. Upon activation, intracellular platelet calcium level rises and platelets undergo a conformational change due to contraction of platelet actin and myosin. Platelets change from smooth discs to spiny spheres with multiple protruding pseudopods thereby increasing the expression of glycoprotein (GP) IIb/IIIa receptors on their cell surface. The activation of these receptors allows crosslinks of fibrinogen to form between platelets initiating a cascade of platelet aggregation with superimposed fibrin thrombus formation.