Pathophysiology for TTP. In physiologic conditions, ultralarge VWF multimers released from endothelial cells are cleaved by ADAMTS13 in smaller VWF multimers, less adhesive to platelets. In TTP, because of the absence of functional ADAMTS13 (either absent by congenital defect or inhibited by specific autoantibodies), ultralarge VWF multimers are released into the blood and bind spontaneously to platelets to form aggregates within the arterial and capillary microvessels. The VWF–platelet aggregates are large enough to form microthrombi inducing tissue ischemia, platelet consumption, and microangiopathic hemolytic anemia (schistocytes on blood smear).