A computational model of chemically and mechanically induced platelet plug formation

Objectives Thrombotic deposition is a major consideration in the development of implantable cardiovascular devices. Recently, it has been experimentally demonstrated that localized changes in the blood shear rate -i.e. shear gradients-play a critical role in thrombogenesis. The goal of the present work is to develop a predictive computational model of platelet plug formation that can be used to assess the thrombotic burden of cardiovascular devices, introducing for the first time the role of shear gradients. We have developed a comprehensive model of platelet-mediated thrombogenesis which includes platelet transport in the blood flow, platelet activation and aggregation induced by both biochemical and mechanical factors, kinetics and mechanics of platelet adhesion, and changes in the local fluid dynamics due to the thrombus growth. Methods A 2D computational model was developed using the multi-physics finite element solver COMSOL 5.6. The model can be described by a coupled set of convection-diffusion-reaction equations. Platelet adhesion at the surface was modeled via flux boundary conditions. Using a moving mesh for the surface, thrombus growth and consequent alterations in blood flow were modeled. In the case of a stenosis, the notions of shear stress induced platelet activation in the contraction zone and shear gradients induced platelet deposition in the expansion zone downstream of the stenosis were studied. Results The model provides the spatial and temporal evolution of platelet plug in the flow field. The computed platelet plug size evolution was validated against literature data. The results confirm the importance of considering both mechanical and chemical aggregation of platelets. Conclusions The developed model represents a potentially useful tool for the optimization of the design of the cardiovascular device flow path.