Classic concepts of thrombosis developed over 100 years ago by Virchow suggest that three basic considerations exist that influence clot formation - alterations in the blood elements, alterations of the vessel wall and alterations in the local flow dynamics. Most of the investigations in the first 75 years centered around the role of the blood elements as primary factors in thromboembolic events. Consequently, most of the developmental work on inhibiting this process focused on factors (primarily pharmacologic) that affected the blood , initially, inhibitors of the coagulation cascade, but more recently, inhibitors of platelet function. Over the last quarter century, much attention has been directed at the role of the endothelial cell and the vascular wall in general in modulating both the initiation and the propagation of thrombosis. In addition, an appreciation of the role of blood flow hemodynamics has evolved. Such studies have led to the growing realization that the local flow dynamics can directly affect the level of activation of both the blood and vascular cells. Moreover, flow dynamics modulates both the arrival and removal rate of coagulation proteins and other blood borne factors that participate in the thrombotic and perhaps, more importantly, the embolic process. A better understanding of the physical and chemical factors that control the initiation, propagation and thrombotic deposits is essential for better control of anticoagulation in patients, especially those who are being treated with artificial devices that contact the blood. In such devices, not only are the coagulation pathways potentially altered due to the presence of various synthetic surfaces, but also, the presence of altered vascular conduits leads to pathologically high hemodynamic stresses, turbulent flow, narrow spaces and areas of flow recirculation of blood elements. These flow irregularities are inherent to the replacement devices that are used to correct cardiovascular abnormalities, such as heart valves, vascular prostheses and rotary heart pumps. Their effects on the blood elements produce varying results ranging from fibrin blood clots in low shear regions to platelet-induced thrombi at high shear conditions. The shear forces can produce embolization at either the cellular level (microparticle formation) with the subsequent exposure of cell receptors complexes, negatively charged phospholipid membranes or gross removal of thrombotic masses. Such cellular materials are transported distally where they may attach to vascular or prosthetic surfaces to continue the activation process or, in the case of large thrombotic masses, may occlude the device conduit or a vascular lumen.