Schema for the procoagulant consequences of VWF self-association. In the arterial circulation, VWF circulates in an inactive globular form until it encounters areas of high shear forces or endothelial cell activation. High shear promotes VWF self-association to tethered VWF strands on endothelial cells. Self-associated VWF is active and binds platelets. This noncovalent VWF/platelet aggregation creates the potential for VWF/platelet-rich emboli into the distal arterial microcirculation. Figure created with Biorender.com.