Research

Blood circulates through the vascular system under pressure and puncture or transection of a blood vessel would lead to rapid outpouring of blood if there were no system to plug the opening and stanch the bleeding. Blood clotting is the physiological process through which the body tries to accomplish this. Because transmural pressure differences vary greatly in the circulatory system and because blood flowing at different speeds through vessels of widely varying diameter leads to great variation in shear stress, the challenges of forming a blood clot to stop the outflow of blood differ substantially in different vascular beds. The system that has evolved to cope with these disparate challenges involves the aggregation of cells (platelets) and the formation of fibrous protein gel (fibrin). In addition, there is a complex, powerful, and tightly regulated enzyme network (the coagulation system) involving reactions on the surfaces of activated platelets, that leads to production of an enzyme, thrombin, that is key both in activated platelets so they can cohere to one another and in forming the protein fibrin from which the fibrin mesh is constructed. Hence, fluid dynamic forces, fluid-mediated transport of cells and proteins, the kinetics and mechanics of inter-platelet bond formation and breaking, the biochemical reactions of the coagulation enzyme network, and the polymerization of fibrin all play roles in blood clot formation to greater or lesser extents in different parts of the vasculature. Failure of this system to produce a clot sufficient to stop blood leakage leads to hemorrhage and can cause serious, even life-threatening, problems and excessive clot formation within blood vessels can occlude those vessels and also cause life-threatening problems including heart attacks and strokes.