Essential role of VWF-aIIbß3 binding in thrombus stability in vessel injury

Qizhen Shi, M.D., Ph.D.
Medical College of Wisconsin and Versiti Blood Research Institute
Milwaukee, WI, U.S.

The interaction between von Willebrand factor (VWF) and platelet integrin αIIbß3 has been challenging to isolate due to its overlap with fibrinogen binding at sites of vascular injury. In this presentation, Qizhen Shi introduces a novel ELISA-based assay to evaluate VWF-αIIbß3 binding, and a CRISPR/Cas9-engineered mouse model expressing a VWF variant that cannot bind αIIbß3. Patient plasma analysis identified reduced VWF-αIIbß3 binding across several von Willebrand disease (VWD) subtypes. In the VWF-RGES mouse model, thrombi formed in response to vascular injury were unstable and prone to frequent embolization, with embolic plug occurrence and size markedly elevated compared to wild-type. These findings highlight the diagnostic utility of the VWF-αIIbß3 assay in characterizing certain forms of VWD and confirm the critical role of VWF-αIIbß3 binding in maintaining thrombus stability at sites of vessel injury.