Hemostasis is the process of sealing a vascular leak through concomitant activation of the blood coagulation cascade and blood platelet adhesion to and activation by the subendothelial extracellular matrix (ECM) proteins.Overall, the studies presented in this dissertation provide novel insights into the biochemical, cellular and biomechanical events governing hemostasis and thrombosis. The results from the studies could be useful in the development of devices and therapeutic strategies that improve the hemostatic safety of anticoagulant and antiplatelet agents.