Development of platelet aggregates at high shear rate driven by von Willebrand Factor

Platelet aggregates develop in high shear rate environments in the vasculature to prevent blood loss or pathologically in partially occluded vessels. The polymer von Willebrand Factor (vWF) is essential for rapid initial attachment of platelets to the wall and each other. It is currently unclear how the chemical and mechanical properties of vWF allow for stable aggregate growth. Experimental limitations and computational challenges in 2D or 3D fluid dynamics models make studying vWF difficult. Thus, we have developed a spatially averaged model that tracks the development of a platelet aggregate in flow as a system of ODEs. We utilize first principle arguments from disciplines such as fluid dynamics and protein kinetics to determine how platelet attachment contributes to aggregate growth. We also utilize tools from probability theory to determine the likelihood of platelet detachment due to the drag force imparted on crosslinking bonds. We find that as shear rate varies, inclusion of platelet-vWF-platelet crosslinking stabilizes the aggregate not only by increasing the total number of crosslinks, but also by allowing platelets to attach without a prior activating signal. Furthermore, we show that the polymeric structure of vWF allows for more stable aggregation compared to the monomer case. These results have implications for aggregation in stenotic regions as well as in disease states such as von Willebrand’s Disease.