Platelets are anucleate, discoid cell fragments measuring 1.5 to 3.0 μM in diameter. They are derived from bone-marrow megakaryocytes that are normally maintained in a nonadhesive state, whereby they circulate freely in blood. Anucleate platelets are unique to mammals, with nonmammalian vertebrates (such as zebrafish) possessing nucleated thrombocytes. In 1865, a German anatomist Max Schultze (1825–1874) first described platelets as “spherules” much smaller than red blood cells. A few years later, in 1882, Giulio Bizzozero (1846–1901) found that platelets played a role in coagulation because they could clump and form a blood clot at the site of vessel wall injury. It was not until 1961, however, that the platelet aggregating effect of adenosine diphosphate was discovered (1) and, in the following year, that a machine for measuring aggregation (an aggregometer) was developed (2). The most important breakthroughs surrounded the discovery of proaggregatory platelet thromboxane A2 (TXA2) and antiaggregatory endothelial cell (EC) prostacyclin (PGI2), both discovered in the 1970s, along with the finding that aspirin inhibited prostaglandin synthesis and platelet activation. Indeed, finding inhibitors to platelets was exciting because it established the therapeutic possibility of preventing arterial thrombosis and ultimately vessel occlusion (the precipitating event in most myocardial infarctions and many strokes) by means of antiplatelet therapy.

The activation of platelets to arrest bleeding at sites of vascular damage results in platelet adhesion to the vessel wall, where they convert from passive, small discs into larger, flattened structures with extended pseudopods that act as a surface for the propagation of the clotting cascade. Activated platelets secrete and synthesize further platelet agonists, inflammatory mediators, and vasoactive substances.