Spatiotemporal dynamics of blood coagulation in medium-sized vessels: numerical insights into the effects of vessel walls and blood flow.

摘要

The spatiotemporal distribution of coagulation factors fundamentally governs blood coagulation dynamics. Although these dynamics have been examined at the submillimeter scale (hundred micrometers), how this distribution influences thrombus formation at dimensions comparable to or larger than those of medium-sized vessels (on the order of 1 mm in diameter) remains insufficiently clarified. In this study, we performed numerical simulations using a well-established reaction-diffusion model of the intrinsic coagulation pathway to investigate coagulation kinetics over millimeter-scale domains, while explicitly incorporating the effects of walls and convection on coagulation. The simulation settings were validated against experimentally observed coagulation behaviors. Our results indicated that in blood domains adjacent to an active wall surface, the propagation velocities of the thrombin wave and the advancing clot front decreased with increasing distance from the wall and approached a constant value at approximately 200µm. This spatial variation in velocity led to domain-size-dependent behavior in the temporal evolution of the volume-averaged thrombin concentration in millimeter-scale domains analyzed in thrombin generation assays because the domain size determined the ratio of the active surface area to blood volume. In addition, simulations of coagulation along a 5 cm-long thin filament within a rat arteriovenous shunt showed a progressive increase in the coagulation rate along the flow direction, indicating that the longitudinal distribution of coagulation activity governs the total clot volume. Together, these findings underscore the need to resolve multiscale spatial distributions of coagulation, from the micrometer to centimeter scales, to improve understanding of thrombus formation under physiological conditions where the effects of walls and convection interact.