The effect of flow on hemostasis and thrombosis

While dilution of procoagulants has generally been proposed as the mechanism by which flow reduces coagulation at surfaces, such a mechanism has never been verified experimentally and, in faet, there are theoretical grounds for suspecting the validity of such a hypothesis. It is quite plausible that flow may have direct effects on certain enzyme or polymerization kinetics involved in thrombosis, in addition to the well-defined effect that flow has an enhancing transport of reactants and products to and from the vessel wall. Such effects of flow on immobilized enzymes have occasionally been observed, but never studied with respect to coagulative processes. The study of the effects of flow on hemostasis and thrombosis, while numerous, are still in their infancy. As noted above, increasing shear increases the rate of formation of factor Xa in a tubular reactor. In the presence of factors VIII and IX, there is also a shear-induced enhancement of Xa production. These studies indicate that at least some coagulation reactions are accelerated in the presence of high shear. However, it has been observed that fibrin formation is diminished at increasing shear rates. This implies that at least one step of the coagulation cascade is being inhibited by high shear. One possibility is that fibrin monomer is being removed by the high local flow conditions, although the concomitant reduction in fibrinopeptide A argues against this interpretation. Another possibility, not yet tested, is that thrombin itself is removed by flow. Finally, we wish to point out that hemostasis, and most likely thrombosis as well, involves the formation of factors IXa and Xa on the vascular wall (the anatomical site of tissue factor). These clotting factors must then be translocated to the platelet surface. This involves three-dimensional processes, convection and diffusion. The relative importance of each has yet to be determined, but it appears likely that each is essential for efficient function of this complex system.