Thrombus formation is closely related to the blood flow. Recent clinical observations suggest that fibrin formation occurs not only in veins (low flow velocity) but also in arteries (high flow velocity). Numerical simulations of the coupling of platelet (PLT) aggregation and blood coagulation demonstrated that fibrin-rich (venous) and PLT-rich (arterial) thrombi form under high and low flow velocities, respectively. In this study, we performed a two-dimensional numerical simulation of blood coagulation in a large vessel due to a thrombin burst to clarify the thrombus formation process under the influences of red blood cells (RBCs). Blood coagulation was expressed by thrombin burst, diffusion and convection of thrombin under blood flow, and fibrin formation as a function of thrombin concentration. The motion of RBCs and PLTs was directly solved using the particle method. The Couette flow between two parallel plates was used to express blood flow near the vessel wall, in which the distance between the two parallel plates was set as large as several hundred microns. Numerical simulations revealed that an RBC-fibrin-rich red thrombus formed under low flow velocity (low Pe), where Pe is the Peclet number as the blood flow velocity relative to thrombin diffusion velocity. PLT-fibrin-rich white thrombus formed in high flow velocity (high Pe). Simulated thrombus structures were consistent with published experimental and clinical observations, reproducing valley and mountain PLT aggregate under high flow velocity, and difference of thrombus component ratios between veins (assuming low Pe) and arteries (high Pe). These results suggest that velocity-dependent kinematics of RBCs relative to thrombin diffusion plays an important role in forming red and white thrombi.

This study was partly funded by Grants-in-Aid for Scientific Research (20K04281, 23H01337), JSPS.