Old concepts and new developments in the study of platelet aggregation

Platelets, anucleated cells that originate from the cytoplasm of bone marrow megakaryocytes (1), circulate through the blood, surveying the integrity of the vascular system. Platelets act in response to traumatic injuries in which the continuity of the vessel wall is interrupted and blood begins to pour outside (2, 3). The arrest of posttraumatic hemorrhage depends on a complex set of regulated events collectively defined as hemostasis, which include the clotting of fibrinogen into insoluble fibrin, as well as platelet adhesion to exposed tissues and to one another with the formation of masses known as thrombi (4). However, neither platelets nor other components of the hemostatic process can distinguish between traumatic wounds and other lesions that may develop in the vessel wall. Thus, when occlusive thrombi form within the vasculature, an otherwise beneficial function, which limits blood loss after tissue injury, becomes a potentially life-threatening disease mechanism. Such a course of events is usually initiated by destabilizing conditions in arteries affected by chronic degeneration, as when an atherosclerotic plaque suddenly ruptures (5, 6). Platelet-rich thrombi that acutely curtail the supply of blood to vital organs may cause death or serious pathological conditions, such as ischemic syndromes of the heart and brain. Knowledge of the mechanisms of platelet function has informed the development of potent and selective antithrombotic drugs, and first-generation antiplatelet compounds that specifically block adhesion receptors have already proved beneficial in the clinic (7–9).