Simulation of thrombosis in a stenotic microchannel: The effects of vWF-enhanced shear activation of platelets

Abstract

This study was undertaken to develop a numerical/computational simulation of von Willebrand Factor (vWF) -mediated platelet shear activation and deposition in an idealized stenosis. Blood is treated as a multi-constituent mixture comprised of a linear fluid component and a porous solid component (thrombus). Chemical and biological species involved in coagulation are modeled using a system of coupled convection-reaction-diffusion (CRD) equations. This study considers the cumulative effect of shear stress (history) on platelet activation. The vWF activity is modeled as an enhancement function for the shear stress accumulation and is related to the experimentally-observed unfolding rate of vWF. A series of simulations were performed in an idealized stenosis in which the predicted platelets deposition agreed well with previous experimental observations spatially and temporally, including the reduction of platelet deposition with decreasing expansion angle. Further simulation indicated a direct relationship between vWF-mediated platelet deposition and degree of stenosis. Based on the success with these benchmark simulations, it is hoped that the model presented here may provide additional insight into vWF-mediated thrombosis and prove useful for the development of more hemo-compatible blood-wetted devices in the future.

A three-dimensional multiscale model for the prediction of thrombus growth under flow with single-platelet resolution

“…Numerous computational models of thrombus growth under flow have been developed in the literature [6][7][8][9][10][11][12][13][14][15][16][17]. While several continuum models of thrombus growth have been developed in 3D, single-platelet resolution models that are necessary to account for the stochastic thrombus morphologies have largely been restricted to 2D representations.…”

Platelet activation via dynamic conformational changes of von Willebrand factor under shear

“…Shear gradients, as well as the duration of exposure to high shear stress, can influence the onset of SIPAct in the presence of VWF molecules [18,28,31,34,43,44]. The haemostatic activity of VWF directly correlates with its size [39,45].…”

Modelling Particle Agglomeration on through Elastic Valves under Flow

“…These sections are contracted periodically to simulate pulsatile blood flow. During typical daily activities, when the muscles in the leg contract, they squeeze the blood flow which promotes blood circulation [2,3]. The pressure generated by the contraction, opens the valve on the right (Figure 2b) and closes the valve on the left.…”

“…These valves consist of two elastic leaflets that open and close in conjunction with the musculoskeletal system. When we are physically active, the muscles in the leg constantly contract and relax, causing the vein valves to open, allowing blood to return to the heart, and close to avoid blood flowing back in the opposite direction [2,3].…”