Reversible formation of von-Willebrand-factor–platelet aggregates in microvascular blood flow

Von Willebrand factor (VWF) and blood platelets play a key role in blood clotting by forming VWF-platelet aggregates. Using mesoscale hydrodynamic simulations, we study the behavior of these aggregates in microvascular blood flow. In microvessels, free VWF molecules and platelets migrate (or marginate) toward the vessel wall, due to the interaction with red blood cells under flow, such that their local concentration near the wall is substantially increased. Then, large shear rates near the wall facilitate the formation and growth of VWF-platelet aggregates. After reaching a certain size, the aggregates experience a hydrodynamic lift force and move away from the wall into the bulk flow, where local shear rates are relatively small, and dissociate reversibly into single components. Consequently, the described process repeats. In addition to the demonstration of recurrent formation and dissociation of VWF-platelet aggregates, our simulations show that shear activation of VWF and the interactions between VWF and platelets are the main determinants of this process. A significant change in the VWF shear activation or VWF-platelet interactions may readily lead to no aggregate formation or to the formation of irreversible aggregates.