A COMPUTATIONAL MODEL OF CHEMICAL AND MECHANICAL PLATELET ACTIVATION AND AGGREGATION

Objectives: Thrombotic deposition is a major consideration in the development of implantable cardiovascular devices. Recently, it has been demonstrated that fluid mechanical shear micro-gradients play a critical role in thrombogenesis. The goal of the present work is to develop a predictive computational model of platelet activation and deposition that can be used to assess the thrombotic burden of cardiovascular devices. We have developed a comprehensive model of platelet-mediated thrombogenesis which includes platelet transport in the blood flow, platelet activation induced by both agonists generated at sites of vascular injury and shear micro-gradients, kinetics and mechanics of platelet adhesion, and changes in the local fluid dynamics due to the growth of a thrombus. Methods: A 2D computational model was developed using the multiphysics finite element solver COMSOL 5.3a. The model can be described by a coupled set of convection-diffusion-reaction equations, and it comprises 7 species: resting and activated platelets, agonists that induce thrombosis, and an anticoagulant agent. 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 stressinduced platelet activation in the acceleration zone and platelet deposition in the expansion zone downstream of the stenosis were studied. Results: The model provides the spatial and temporal evolution of thrombosis in the flow field. The computed density of platelets adherent to the surface was validated against experimental data. The results confirm the importance of considering both mechanical and chemical activation of platelets. Discussion: The developed model represents a potentially useful tool for the optimization of the design of the cardiovascular device flow path.