Figure 1: The role of ADAMTS13 in normal hemostasis. Upon stimulation or vascular injury, UL-VWF is released from endothelial cells or adhered to sub-endothelial collagen matrix. Platelets are recruited to the sites of activation or injury via interaction with UL-VWF. While cleavage of cell bound UL-VWF does not require shear, fluidic shear stress accelerates the removal or cleavage of UL-VWF on endothelium and at the sites of thrombus formation. Binding of platelets and/or coagulation factor VIII to UL-VWF or soluble VWF dramatically enhances its proteolytic cleavage by ADAMTS13 under flow. This regulated process of ULVWF or large soluble VWF by ADAMTS13 is essential for maintaining normal blood flow. Deficiency of plasma ADAMTS13 activity either resulting from mutations in ADAMTS13 gene or acquired autoantibodies against ADAMTS13 results in accumulation of UL-VWF on endothelium and at the sites of injury, leading to exaggerated platelet aggregation and thrombus formation in small arterioles and capillaries, the characteristic pathological feature of TTP.