The function of ultra-large von Willebrand factor multimers in high shear flow controlled by ADAMTS13

SummaryThe paradigm that platelet aggregation, which contributes to bleeding arrest and also to thrombovascular disorders, initiates after signaling-induced platelet activation has been refuted in past recent years. Platelets can form aggregates independently of activation when soluble von Willebrand factor (VWF) is present and the shear rate exceeds a certain threshold where active A1 domains become exposed in soluble VWF multimers and can bind to platelet glycoprotein Ib. Subsequently – fostering each other – VWF can self-assemble into large nets combining with platelets into large conglomerates, which are ent…