Volume 9, Number 8, November 2002

The role of platelets and antiplatelet therapy in atherothrombotic disease
Alison H Goodall

Platelet-initiated thrombus plays a central role in the pathogenesis of arterial thrombotic disease. Platelets are activated by a range of physiological agonists including thrombin, ADP, thromboxane and collagen, acting in co-operation. ADP, though a weak agonist on its own, is important in enhancing platelet activation induced by other agents. Activation results in platelet adhesion, aggregation and degranulation leading to thrombus growth. Platelets also reinforce thrombus formation through platelet-mediated thrombin generation and the release of PAI-1 that inhibits fibrinolysis. Antiplatelet therapy is therefore of potential benefit both prior to and during a thrombotic episode. The commonly used antiplatelet drugs inhibit specific, single pathways of platelet activation but have overall benefit. Inhibition of intracellular activation pathways can be achieved with aspirin (which inhibits platelet cyclo-oxygenase) and dipyridamole (which inhibits phosphodiesterase). Two related thienopyridine derivatives, ticlopidine and clopidogrel, are specific inhibitors of the P2Y₁₂ ADP receptor. They have comparable pharmacological activity but clopidogrel has a better safety profile. A number of potent glycoprotein IIb/IIIa antagonists have been developed for therapeutic use. They are effective in percutaneous coronary intervention, though data from primary stenting trials are less positive. The recent update of the meta-analysis of trials of antiplatelet therapy by the Antithrombotic Trialists’ Collaboration has confirmed the benefit of antiplatelet therapy in secondary prevention.

Br J Cardiol 2002;9:S2-S7.

View full PDF article (open in new window)
Email this article