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 the flow environment on platelet aggregation is not fully understood in high-shear thrombosis. The objective of this study is to investigate the role of a high shear rate in initial platelet aggregation. The haemodynamic conditions in a microfluidic device are studied using cell-based blood flow simulations. The results are compared with in vitro platelet aggregation experiments performed with porcine whole blood (WB) and platelet-rich-plasma (PRP). We studied whether the cell-depleted layer in combination with high shear and high platelet flux can account for the distribution of platelet aggregates. High platelet fluxes at the wall were found in silico . In WB, the platelet flux was about twice as high as in PRP. Additionally, initial platelet aggregation and occlusion were observed in vitro in the stenotic region. In PRP, the position of the occlusive thrombus was located more downstream than in WB. Furthermore, the shear rates and stresses in cell-based and continuum simulations were studied. We found that a continuum simulation is a good approximation for PRP. For WB, it cannot predict the correct values near the wall.

No abstract

Occlusive thrombi formed under high flow shear rates develop very rapidly in arteries and may lead to myocardial infarction or stroke. Rapid platelet accumulation (RPA) and occlusion of platelet-rich thrombi and clot shrinkage have been studied after flow arrest. However, the influence of margination and shear rate on occlusive clot formation is not fully understood yet. In this study, the influence of flow on the growth and shrinkage of a clot is investigated. Whole blood (WB) and platelet-rich plasma (PRP) were perfused at high shear rates (> 3,000 s−1) through two microfluidic systems with a stenotic section under constant pressure. The stenotic section of the two devices are different in stenotic length (1,000 vs 150 μm) and contraction angle of the stenosis (15° vs 80°). In all experiments, the flow chamber occluded in the stenotic section. Besides a significantly increased lag time and decreased RPA rate for PRP compared to WB (p < 0.01), the device with a shorter stenotic section and steeper contraction angle showed a shear-dependent occlusion and lag time for both PRP and WB. This shear-dependent behavior of the platelet aggregate formation might be caused by the stenotic geometry.

Ballistocardiography is a non-invasive technique to estimate heart function and relative changes in cardiac output. The goal of this study was to establish the relationship between ballistocardiogram (BCG) parameters and changes in cardiovascular parameters. A group of 20 subjects performed three different exercises on a force plate. In this study, we have characterized the significant differences induced by static and dynamic squats, and controlled respiration exercises on BCG parameters such as IJ-amplitude and RJ-time. The dynamic squat exercise induced the largest changes in IJ-amplitude (107-123% higher) and the RJ-time (21-23% lower). Furthermore, the IJ-amplitude of the BCG signal was found to be positively related to the cardiac output.