Introduction

Platelet aggregation is involved in the formation of hemostatic plugs and arterial thrombi. Under normal circumstances, platelets are non-adhesive and circulate singly, but following vessel wall injury they adhere to the injury site and to each other. During the hemostatic process, platelet aggregates, stabilized by fibrin, arrest bleeding from injured or severed vessels. In contrast to this useful function, platelet aggregates that form on injured vessels, on ruptured atherosclerotic plaques, or in regions of high shear contribute to the narrowing of blood vessels. If thrombi are unstable, they may embolize and block smaller vessels downstream from an injury site. Since platelet aggregation has a major role in the clinical complications of atherosclerosis (myocardial infarction, ischemic stroke, and peripheral vascular disease), there is intensive study of the processes involved in platelet aggregation and of inhibitors of platelet activation.

In vivo, activators of platelets include the agonists that are listed in Table 23.1. Receptors for some of the most important agonists are discussed in Chapters 8–11. Aggregating agents can act singly, and are frequently studied singly in vitro, but in vivo they undoubtedly act in concert with each other in a process described as synergism. Synergistic responses result in a combined effect that is greater than the additive effects of the single stimuli. In vivo, the most important aggregating agents are collagen in the vessel wall, ADP from red blood cells or released from the platelets themselves, thromboxane A2 formed by stimulated platelets, and thrombin, although other agonists such as serotonin may contribute to the aggregation process.