Identifying the start of a platelet aggregate by the shear rate and the cell-depleted layer

Abstract

Computer simulations were performed to study the transport of red blood cells and platelets in high shear flows, mimicking earlier published in vitro experiments in microfluidic devices with high affinity for platelet aggregate formation. The goal is to understand and predict where thrombus formation starts. Additionally, the need of cell-based modelling in these microfluidic devices is demonstrated by comparing our results with macroscopic models, wherein blood is modelled as a continuous fluid. Hemocell, a cell-based blood flow simulation framework is used to investigate the transport physics in the microfluidic devices. The simulations show an enlarged cell-depleted layer at the site where a platelet aggregate forms in the experiments. In this enlarged cell-depleted layer, the probability to find a platelet is higher than in the rest of the microfluidic device. In addition, the shear rates are sufficiently high to allow for the von Willebrand factor to elongate in this region. We hypothesize that the enlarged cell-depleted layer combined with a sufficiently large platelet flux and sufficiently high shear rates result in an haemodynamic environment that is a preferred location for initial platelet aggregation.

The influence of red blood cell deformability on hematocrit profiles and platelet margination

“…HemoCell has been validated to reproduce the mechanical responses of an individual, healthy, RBC induced by sheared flow and optical tweezers, as well as accurately reproducing bulk flow hallmarks of whole blood such as the Fåhraeus-Lindqvist effect and the CFL [31]. With this validated RBC model HemoCell has been used to study the effects of RBC cytoplasmic viscosity contrasts in bulk flow [32], the role of hematocrit profiles on cell diffusivities in flow [33], as well as identifying the start of a platelet aggregate [40]. The capabilities of HemoCell allow the tracking of the individual suspended healthy RBCs, stiffened RBCs, and platelets that are present in the in vitro experiments reported in this study.…”

Haemodynamic flow conditions at the initiation of high-shear platelet aggregation: a combined in vitro and cellular in silico study

“…The xy -component of the shear rate and stress were both derived from the flow field, because in this geometry the other components are negligibly smaller in comparison. The platelet count per second and platelet residence times were derived as described in [ 11 ]. The platelet count per second or platelet flux is the average number of platelets that were present on a certain location in the domain measured every 100 000 time steps divided by the total time of all time steps.…”

“…However, it is difficult to obtain the exact values of shear rates and stresses in these devices. Previously, we found that shear rates are underestimated and shear stresses overestimated in continuum simulations assuming blood as a Newtonian fluid with a constant viscosity [ 11 ]. Since most researchers [ 4 , 5 , 12 , 13 ] used this assumption, there is a clear need to investigate the details of the flow domain and flow conditions in the microfluidic experiments in high-shear thrombosis.…”

“…Previously, we have shown that a cell-depleted layer in combination with high shear and a high platelet density might be a possible indicator for high-shear thrombosis [ 11 ]. In this study, we compare the cell-free layer from numerical transport modelling with experimental results on initial platelet aggregation.…”

In Silico Hemostasis Modeling and Prediction

“…23 The redistribution of RBCs and platelets in the case of disturbed flow (for example provided by vessel stenosis) was also suggested to influence the primary kinetics of platelet adhesion. 24 Continuous models describing platelet adhesion using the RBC-platelet interaction-induced flux of the platelet "substance" to the vessel wall or to the surface of platelet aggregates formed as a result of such a flux have been used to study the dynamics of occlusive thrombus formation in the stenosed arteries. 25 It is now clear that the first steps of platelet-dependent response are driven by purely mechanical processes of the interaction of platelet surface receptors (GPIbalpha and integrins) with their ligands on the surface of the injured vessel wall (von Willebrand factor [vWF], fibrinogen, fibronectin, laminins, etc.).…”