Simplified model of VWF and ADAMTS13 plasma levels and their contribution to thrombotic events. At sites of injury, VWF becomes immobilized on the damaged vessel wall allowing platelet tethering by the GPIb-VWF interaction (not depicted), which in turn enables platelet activation and thrombus growth to seal a wound (normal hemostasis). Released ultra-large (UL)–VWF can be cleaved by ADAMTS13 into less-reactive smaller VWF multimers to limit thrombus growth. High VWF or low ADAMTS13 plasma levels are each a risk factor for the development of ischemic stroke (IS) and myocardial infarction (MI). The combination of both high VWF and low ADAMTS13 plasma levels further increases the risk of a thrombotic event.