Computational simulation of platelet interactions in the initiation of stent thrombosis due to stent malapposition.

Coronary stenting is one of the most commonly used approaches to open coronary arteries blocked due to atherosclerosis. Stent malapposition can induce thrombosis but the microscopic process is poorly understood. The objective of this study was to determine the platelet-level process by which different extents of stent malapposition affect the initiation of stent thrombosis. We utilized a discrete element model to computationally simulate the transport, adhesion, and activation of thousands of individual platelets and red blood cells during thrombus initiation in stented coronary arteries. Simulated arteries contained a malapposed stent with a specified gap distance (0, 10, 25, 50, or 200 µm) between the struts and endothelium. Platelet-level details of thrombus formation near the proximal-most strut were measured during the simulations. The relationship between gap distance and amount of thrombus in the artery varied depending on different conditions (e.g., amount of dysfunctional endothelium, shear-induced activation of platelets, and thrombogenicity of the strut). Without considering shear-induced platelet activation, the largest gap distance (200 µm) produced no recirculation and less thrombus than the smallest two gap distances (0 and 10 µm) that created recirculation downstream of the strut. However, with the occurrence of shear-induced platelet activation, the largest gap distance produced more thrombus than the two smallest gap distances, but less thrombus than an intermediate gap distance (25 µm). A large gap distance was not necessarily the most thrombogenic, in contrast to implications of some computational fluid dynamics studies. The severity of stent malapposition affected initial stent thrombosis differently depending on various factors related to fluid recirculation, platelet trajectories, shear stress, and endothelial condition.