Projecting a dual role for platelet GPIbα in regulating ADAMTS13-mediated proteolysis of VWF. First, GPIbα binding to VWF A1 removes an inhibitory constraint of ADAMTS13-dependent A2 proteolysis at Tyr842/Met843. Second, binding of 2 or more platelets to an individual VWF multimer through GPIbα stretches the flexible A2 domain under shear to facilitate ADAMTS13 cleavage of A2, thereby decreasing the prothrombotic activity of high-molecular-weight multimers.