Examining platelet adhesion via Stokes flow simulations and microfluidic experiments

Abstract

While critically important, the platelet function at the high shear rates typical of the microcirculation is relatively poorly understood. Using a large scale Stokes flow simulation, Zhao et al. recently showed that RBC-induced velocity fluctuations cause platelets to marginate into the RBC free near-wall region [Zhao et al., Physics of Fluids, 2012, 24, 011902]. We extend their work by investigating the dynamics of platelets in shear after margination. An overall platelet adhesion model is proposed in terms of a continuous time Markov process and the transition rates are established with numerical simulations involving platelet-wall adhesion. Hydrodynamic drag and Brownian forces are calculated with the boundary element method, while the RBC collisions are incorporated through an autoregressive process. Hookean springs with first order bond kinetics are used to model receptor-ligand bonds formed between the platelet and the wall. The simulations are compared with in vitro microfluidic experiments involving platelet adhesion to Von Willebrand Factor (VWF) coated surfaces.

The Effect of Hematocrit on Platelet Adhesion: Experiments and Simulations

“…These articles model platelet adhesion as occurring from Hookean springs with given equilibrium lengths that attach and detach stochastically according to first-order rate constants. Fitzgibbon et al (30) used a similar model with no equilibrium length of the spring to show that their simulations could replicate the experimentally determined length distribution of translocation distances of individual rolling platelets before they finally adhered to a wall.…”

Platelet behaviour on von Willebrand Factor changes in pregnancy: Consequences of haemodilution and intrinsic changes in platelet function

“…As HCT and flow rate increased, driving platelets towards the vessel wall, there was a concomitant increase in platelet adhesion to VWF 19 . Our group more recently verified the importance of HCT and flow rate in determining initial platelet adhesion to VWF using Stokes flow simulations and microfluidic flow experiments 16 . At arterial shear flow (1500 s −1 ), a higher HCT was associated with greater numbers of platelet/RBC collisions.…”

“…3A). Platelet interactions with the chamber wall are driven in part by the process of margination, wherein the red blood cells (RBCs) force the smaller platelets to the periphery of the flowing blood stream 16 . There was no change in the speeds that platelet’s translocated across the surface as HCT was reduced ( p  = 0.8709; r 2  = 0.0002, Fig.…”

“…Platelet collisions with RBCs reduced the time needed for platelets to migrate through the cell-free layer towards the wall of the vessel. As more platelets presented at the vessel wall, the number of platelet interactions with VWF also increased 16 .…”

Effect of Cytoplasmic Viscosity on Red Blood Cell Migration in Small Arteriole-level Confinements

“…This layer is known to contribute in the reduction of the blood viscosity or plasma skimming as blood perfuses the smaller vessels (Freund, 2014;Pries and Secomb, 2003). In addition, the migration of the red blood cells induces the margination of stiffer platelets by volume exclusion (Spann et al, 2016;Fitzgibbon et al, 2015;Reasor et al, 2013;Vahidkhah, 2015;Haga et al, 1998;Bächer et al, 2018). These marginated platelets are now better located to participate in reactions with the endothelial cells in the event of an injury when the clotting cascade begins (Mitrophanov et al, 2014;Govindarajan et al, 2016).…”