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The paper reviews the state-of-the-art in computational modeling of thrombus formation and growth and related phenomena including platelet margination, activation, adhesion, and embolization. Presently, there is a high degree of empiricism in the modeling of thrombus formation. Based on the experimentally observed physics, the review gives useful strategies for predicting thrombus formation and growth. These include determining blood components involved in atherosclerosis, effective blood viscosity, tissue properties, and methods proposed for boundary conditions. In addition to the guidelines, ongoing research on the effect of shear stress on platelet margination, activation and adhesion, and platelet-surface interactions are reviewed. Biotechnol. Bioeng. 2017;114: 2154-2172. © 2017 Wiley Periodicals, Inc.

Shear stresses play a major role in platelet-substrate interactions and thrombus formation and growth in blood flow, where under both pathological and physiological conditions platelet adhesion and accumulation occur. In this study, a shear-dependent continuum model for platelet activation, adhesion and aggregation is presented. The model was first verified under three different shear conditions and at two heparin levels. Three-dimensional simulations were then carried out to evaluate the performance of the model for severely damaged (stripped) aortas with mild and severe stenosis degrees in laminar flow regime. For these cases, linear shear-dependent functions were developed for platelet-surface and platelet-platelet adhesion rates. It was confirmed that the platelet adhesion rate is not only a function of Reynolds number (or wall shear rate) but also the stenosis severity of the vessel. General correlations for adhesion rates of platelets as functions of stenosis and Reynolds number were obtained based on these cases. Finally using the new platelet adhesion rates, the model was applied to different experimental systems and shown to agree well with measured platelet deposition.

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In this study, a shear-dependent continuum model for platelet activation, adhesion and aggregation is validated using computational fluid dynamics (CFD). To take the presence of red cells into account, a combination of excess-platelet boundary layer and enhanced mass diffusivity of platelets and large species is used to mimic this behavior. The model has been validated under three different shear conditions and two different heparin levels. Also three-dimensional simulations were carried out to evaluate the model’s prediction of thrombus growth rate for stenosed tubes under various flow conditions and stenosis degrees. For these cases, also the effect of change in platelet diffusivity has been investigated by using an empirical correlation for enhanced diffusivity of platelets. For all 3D simulations, results for thrombus growth rate as a function of local wall shear rate were compared to those of experiments and numerical studies in the literature and an acceptable agreement was achieved.