THE EFFECT OF FLOW AND MASS-TRANSPORT IN THROMBOGENESIS

The paper presents a mathematical analysis of the contributions of flow and mass transport to a single reactive event at a blood vessel wall. The intent is to prepare the ground for a comprehensive study of the intertwining of these contributions with the reaction network of the coagulation cascade. We show that in all vessels with local mural activity, or in "large" vessels (d > 0.1 mm) with global reactivity, events at the tubular wall can be rigorously described by algebraic equations under steady conditions, or by ordinary differential forms (ODEs) during transient conditions. This opens up important ways for analyzing the combined roles of flow, transport, and coagulation reactions in thrombosis, a task hitherto considered to be completely intractable. We report extensively on the dependence of transport coefficient k(L) and mural coagulant concentration C(w) on flow, vessel geometry, and reaction kinetics. It is shown that for protein transport, k(L) varies only weakly with shear rate gamma in large vessels, and not at all in the smaller tubes (d < 10(-2) mm). For a typical protein, k(L) approximately 10(-3) cm s-1 within a factor of 3 in most geometries, irrespective of the mural reaction kinetics. Significant reductions in k(L) (1/10-1/1,000) leading to high-coagulant accumulation are seen mainly in stagnant zones vicinal to abrupt expansions and in small elliptical tubules. This is in accord with known physical observations. More unexpected are the dramatic increases in accumulation which can come about through the intervention of an autocatalytic reaction step, with C(w) rising sharply toward infinity as the ratio of reaction to transport coefficient approaches unity. Such self-catalyzed reactions have the ability to act as powerful amplifiers of an otherwise modest influence of flow and transport on coagulant concentration. The paper considers as well the effect on mass transport of transient conditions occasioned by coagulation initiation or pulsatile flow. During initiation, instantaneous flux varies with diffusivity and bulk concentration, favouring the early adsorption/consumption of proteins with the highest abundance and mobility. This is akin to the 'Vroman effect' seen in narrow, stagnant spaces. The effect of flow pulsatility on k(L) has the potential, after prolonged cycling, of bringing about segregation or accumulation of proteins, with consequences for the coagulation process.