Platelet aggregation in complex vessel geometries An in silico study on cellular blood flow mechanics

Cardiovascular diseases are the primary cause of death worldwide. One process contributing to multiple types of cardiovascular disease is thrombosis, which refers to the pathologic growth of a blood clot inside a vessel. To avoid, slow down or reverse thrombosis, there is ongoing research focusing on anti-thrombotic therapies targeting different thrombotic pathways. One specific challenge in the development of anti-thrombotic treatments is to maintain the functionality of the healthy blood clotting process hemostasis, as both follow similar pathways including the aggregation of platelets. The aim of this thesis is to study cellular flow mechanics of whole blood in microscale vessel geometries to improve the understanding of the biomechanical pathways of platelet aggregation. To achieve this, cell-resolved blood flow simulations are deployed. Beginning in Chapter 2, the effects of micro-channel curvature on cellular blood flow are investigated and possible implications for platelet adhesion and aggregation are discussed. In Chapter 3, geometrical scale and complexity of the simulated domain are increased and the potentially hemostatic environment of a vessel micropuncture is studied. The work of Chapter 4 further increases the spatial scale of the simulations and shifts closer towards clinical application: the chapter includes the comparison between two different carotid stent designs and attempts an early assessment on potential thrombotic risk factors. Chapter 5 sets out to combine the work of the previous chapters by introducing a cellular platelet adhesion and aggregation model, to investigate the influence of a growing aggregate on the local flow environment. Finally, Chapter 6 summarizes and concludes the work of this thesis, provides overview on how investigations on the presented studies could be continued further and gives a general outlook on the possible future directions of cellular blood flow modelling.