Platelet adhesion and aggregation in high shear blood flow An in silico and in vitro study

Our body prevents us from bleeding by the formation of a blood clot. However, when a blood clot continues to grow, it can obstruct a blood vessel. This process is called thrombosis and may lead to disability or dead. The following three components are necessary in arterial thrombosis: a thrombogenic surface, high shear rates and the biological components: von Willebrand factor and platelets. In this dissertation the influence of blood flow on initial aggregation of platelets is studied. In order to do so, cell-based simulations and in vitro experiments are used. The local flow environment in in vitro experiments on platelet aggregation are studied with simulations. A hypothesis was formulated and tested in this dissertation: a combination of high shear rate, high platelet flux, and the presence of a cell-depleted layer are possible indicators for a favorable environment for the start of a platelet aggregate formation. In addition, in vitro platelet aggregation experiments were performed to study the importance of flow environment on platelet aggregation. Two microfluidic devices were used with a different geometry and thus a different flow environment. Lag times, occlusion times and rapid platelet accumulation (RPA) rates were measured and compared among porcine whole blood and platelet-rich plasma experiments. New insights were gained in the relation between blood flow parameters, i.e. shear rate and platelet availability, and platelet aggregation from both in vitro experiments and cell-based simulations.