No abstract

Platelets contribute to normal hemostasis by adhering to subendothelial tissues after vascular damage has taken place and then recruiting additional platelets through the process of aggregation. Activation of the coagulation cascade ultimately results in fibrin deposition. In pathological conditions, thrombogenic surfaces act as a nidus for platelet adherence and thrombus formation. The ability of platelet-inhibiting agents to prevent or impair platelet-mediated thrombotic and thromboembolic events is of vital importance in the prevention and treatment of cardiovascular diseases, including myocardial infarction, unstable angina and stroke. They also serve as important adjuvants following percutaneous transluminal coronary angioplasty and saphenous vein bypass grafting. Future investigations will likely uncover additional indications.

The fundamental determinants of coronary blood flow include the vessel radius, pressure gradient, and the physical characteristics of the cellular components and fluid medium. Specifically, cellular rheology and plasma viscosity determine, to a significant degree, both macro- and microcirculatory blood flow, particularly when either is compromised by existing atherosclerotic narrowing or reperfusion injury. Among individuals with coronary heart disease, abnormalities in cellular rheology and plasma viscosity may be the best predictors of subsequent cardiac events. Therefore, efforts to limit morbidity and mortality may depend on a more in-depth understanding of these basic areas.

The vascular endothelium, once believed to act solely as a mechanical barrier is, in fact, the body’s most active paracrine organ serving a vital role in vasomotion and thromboresistance. Vasoactive compounds such as prostacyclin and endothelium-derived relaxing factor maintain coronary blood flow in response to physiologic demands, while their antiplatelet effects act along with tissue plasminogen activator and heparin-like species to prevent local thrombus formation. Structural and functional endothelial abnormalities may predispose to vascular thrombosis or impair normal vasodilatory responses to increasing metabolic demands. Acquired endothelial dysfunction following coronary reperfusion, aortocoronary bypass grafting and balloon angioplasty plays a vital role in short- and long-term patient outcome. Future therapies in cardiovascular disease must consider strategies to preserve and facilitate the structural and functional integrity of the vascular endothelium.

In general terms, thrombotic disorders of the cardiovascular system are characterized by poorly regulated, nonphysiologic thrombus formation. Considered more specifically, however, pathologic thrombosis represents a critical imbalance, frequently at both the systemic and vascular levels, of coagulation, anticoagulation and fibrinolysis. Indeed, the balance is shifted toward coagulation, preventing normal physiologic blood flow. Anticoagulants have been a mainstay in the treatment of thrombotic disorders. However, emerging strategies have focused primarily on thrombus dissolution (fibrinolysis), which can be efficiently achieved with the administration of extrinsic plasminogen activators. Clearly, thrombolytic therapy is currently the most direct means of restoring blood flow, vital organ perfusion and hemostatic balance among patients with thrombotic disorders of the cardiovascular system.