Novel mechanisms mediating platelet, coagulation and extracellular matrix interactions in the presence of shear

The prevention and treatment of cardiovascular disease complications, including occlusive blood clots responsible for heart attacks and strokes, are projected to cost Americans more than $500 billion in 2010. While therapeutic strategies have been employed to prevent occlusive events, the most effective antithrombotic agents are accompanied by unintended bleeding side effects. In order to develop new approaches that distinguish pathological events (thrombosis) from physiological clotting (hemostasis), there exists a need for a deeper understanding of the interactions between the major players involved in hemostasis and thrombosis: platelets, coagulation factors and extracellular matrix (ECM) components. In this thesis, we employed flow chamber studies, clotting assays and biochemical and microscopy techniques in order to identify the mechanisms governing the molecular interactions between platelets, coagulation factors and the ECM.