Abstract-Platelets are heterogeneous with respect to their size, density, and reactivity. Large platelets are more active hemostatically, and platelet volume has been found to be increased both in patients with unstable angina and with myocardial infarction. Furthermore, platelet volume is a predictor of a further ischemic event and death when measured after myocardial infarction. Platelets which are anucleate cells with no DNA are derived from their precursor, the megakaryocyte. Therefore, it is suggested that changes in platelet size are determined at thrombopoiesis in the megakaryocyte and that those changes might precede acute cardiac events. Understanding of the signaling system that controls platelet production may also further elucidate the cascade of events leading to acute vascular occlusion in some patients. (Arterioscler Thromb Vasc Biol. 1999;19:672-679.)Key Words: platelets Ⅲ myocardial infarction Ⅲ unstable angina Ⅲ coronary heart disease Ⅲ thrombosis T he biological events that occur in the coronary artery that immediately precede acute coronary syndromes are still not clear. However, platelets are involved, and changes in platelets may be a causal factor in producing a thrombus in the coronary artery.Aspirin is the most widely used antiplatelet drug. As platelets have no nucleus and are therefore unable to synthesize protein de novo, an aspirin-induced functional defect lasts for the whole life span of the platelets (8 to 10 days). 1 The results of large trials 2-4 of the beneficial effect of aspirin treatment in patients with unstable angina are consistent with the hypothesis that platelet activity is causally related to acute coronary syndromes. Both the medium-(12 weeks) 2 and long-term (2 years) 3 risk of cardiac death and myocardial infarction (MI) in patients with unstable angina is reduced. More recently, the significant benefit of antiplatelet therapy with aspirin in protection against acute cardiovascular syndromes and death was further supported in an overview of 145 randomized trials by the Antiplatelet Trialists' Collaboration. 5 Given the known effects of aspirin as an inhibitor of platelet function, these trials are strong evidence that platelets may contribute to the pathophysiology of the acute complications of coronary artery disease. Aspirin is an inhibitor of only one of several specific pathways leading to platelet activation and aggregation. 1 Inhibition of the glycoprotein (GP) IIb/IIIa receptor blocks the binding of fibrinogen, which is the final common pathway of platelet aggregation. 6 Integrelin, which is a GP IIb/IIIa receptor inhibitor, was evaluated in 227 patients with unstable angina and reduced significantly the number and duration of Holter-recorded ischemia compared with aspirin therapy. 7 These recent data are further strong support for the pivotal role of platelets in patients with unstable angina.Circulating platelets are heterogeneous in size, density, and reactivity. 8,9 Changes in these variables may be causal in acute coronary syndromes. 10 Initial plaque ...