Schematic illustration of a potential mechanism of cleavage of ULVWF string by ADAMTS-13 metalloprotease. On stimulation, endothelial cells release contents from the Weibel-Palade bodies. Membrane-bound P-selectin anchors ULVWF multimers to the surface of endothelial cells to allow long stringlike structures to form under flow. Fluid shear stress stretches these strings to expose sites for ADAMTS-13 to adhere to ULVWF and/or cleavage site in the A2 domain of ULVWF. The cleavage releases ULVWF from endothelial cells (and from wall shear stress) to allow cleaved VWF to adopt different conformation that is no longer available for further cleavage.