  Thrombosis under high-shear conditions is mediated by the mechanosensitive
blood glycoprotein von Willebrand Factor (vWF). vWF unfolds in response to
strong flow gradients and facilitates rapid recruitment of platelets in flowing
blood. While the thrombogenic effect of vWF is well recognized, its
conformational response in complex flows has largely been omitted from
numerical models of thrombosis. We recently presented a continuum model for the
unfolding of vWF, where we represented vWF transport and its flow-induced
conformational change using convection-diffusion-reaction equations. Here, we
incorporate the vWF component into our multi-constituent model of thrombosis,
where the local concentration of stretched vWF amplifies the deposition rate of
free-flowing platelets and reduces the shear cleaning of deposited platelets.
We validate the model using three benchmarks: in vitro model of
atherothrombosis, a stagnation point flow, and the PFA-100, a clinical blood
test commonly used for screening for von Willebrand Disease (vWD). The
simulations reproduced the key aspects of vWF-mediated thrombosis observed in
these experiments, such as the thrombus location, thrombus growth dynamics, and
the effect of blocking platelet-vWF interactions. The PFA-100 simulations
closely matched the reported occlusion times for normal blood and several
hemostatic deficiencies, namely, thrombocytopenia, vWD Type 1, and vWD Type 3.
Overall, the multi-constituent model of thrombosis presented in this work
enables macro-scale 3-D simulations of thrombus formation in complex geometries
over a wide range of shear rates and accounts for qualitative and quantitative
hemostatic deficiencies in patient blood. The results also demonstrate the
utility of the continuum model of vWF unfolding that could be adapted to other
numerical models of thrombosis.
