title: Vascular biology of thrombosis: the role of platelet-vessel wall adhesion.
abstract: Arterial thrombosis is initiated after atherosclerotic plaque rupture. The ruptured plaque triggers a cascade of platelet-mediated events that result in the formation of a platelet-rich thrombus. Thrombus development ultimately leads to vessel occlusion, the precipitating event in most myocardial infarctions and many strokes. Arterial thrombosis involves a process of platelet adhesion, activation, and aggregation. Platelets first form a monolayer by adhering to blood vessel subendothelial matrix proteins (collagen and von Willebrand factor) via interactions with platelet membrane glycoprotein (GP) receptors. This interaction produces an intracellular signal that activates platelets to increase expression of a specific GP receptor, GPIIb/IIIa, with a high affinity for fibrinogen and other adhesion molecules. Binding of fibrinogen to adjacent platelets results in irreversible platelet aggregation and the formation of the platelet aggregate. Understanding of this process has led to considerable research into potential antiplatelet compounds. A number of effective antiplatelet drugs are now available, which affect different stages along the platelet adhesion/activation/aggregation pathway. These include aspirin, dipyridamole, and the adenosine diphosphate antagonists. Much effort is now focused on development of thrombin receptor antagonists. However, this is proving to be difficult. Considerable interest has surrounded a new class of platelet drugs, the GPIIb/IIIa receptor antagonists. These drugs have proved effective in short-term infusion trials. However, long-term studies of oral GPIIb/IIIa receptor antagonists have shown increases in mortality. It is believed that these antagonists may act as partial agonists and may increase the risk for thrombosis.
authors.affiliation: Centre for Cardiovascular Science, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: D J
authors.initials: DJ
authors.lastname: Fitzgerald
mesh_terms: D002536:Cerebral Arteries / Q000503:physiopathology*; D006801:Humans; D020767:Intracranial Thrombosis / Q000503:physiopathology*; D010973:Platelet Adhesiveness / Q000502:physiology*; D020521:Stroke / Q000503:physiopathology*