Normal haemostasis is an important physiological mechanism that prevents excessive bleeding during trauma, whereas the pathological thrombosis especially in diabetics leads to increased incidence of heart attacks and strokes as well as peripheral vascular events. In this work, we propose a new multiscale framework that integrates seamlessly four key components of blood clotting, namely transport of coagulation factors, coagulation kinetics, blood cell mechanics and platelet adhesive dynamics, to model the development of thrombi under physiological and pathological conditions. We implement this framework to simulate platelet adhesion due to the exposure of tissue factor in a three-dimensional microchannel. Our results show that our model can simulate thrombin-mediated platelet activation in the flowing blood, resulting in platelet adhesion to the injury site of the channel wall. Furthermore, we simulate platelet adhesion in diabetic blood, and our results show that both the pathological alterations in the biomechanics of blood cells and changes in the amount of coagulation factors contribute to the excessive platelet adhesion and aggregation in diabetic blood. Taken together, this new framework can be used to probe synergistic mechanisms of thrombus formation under physiological and pathological conditions, and open new directions in modelling complex biological problems that involve several multiscale processes.

正常止血是防止创伤期间过度失血的重要生理机制，而病理性血栓形成（尤其是糖尿病患者）会导致心脏病、中风以及外周血管事件的发生率增加。在这项工作中，我们提出了一个新的多尺度框架，无缝集成了血液凝固的四个关键组成部分，即凝血因子的运输、凝血动力学、血细胞力学和血小板粘附动力学，以模拟生理和病理条件下血栓的发展。我们实现这个框架来模拟由于组织因子在三维微通道中暴露而导致的血小板粘附。我们的结果表明，我们的模型可以模拟流动血液中凝血酶介导的血小板活化，导致血小板粘附到通道壁的损伤部位。此外，我们模拟了糖尿病血液中的血小板粘附，结果表明，血细胞生物力学的病理改变和凝血因子数量的变化都导致了糖尿病血液中血小板的过度粘附和聚集。总而言之，这个新框架可用于探索生理和病理条件下血栓形成的协同机制，并为涉及多个多尺度过程的复杂生物问题建模开辟新方向。