Modulation of von Willebrand Factor by ADAMTS13

Existence of the metalloprotease now known to be ADAMTS13 was first established in 1996 through studies investigating the pathogenesis of thrombotic thrombocytopenic purpura (TTP). Since then, considerable progress has been made into unraveling the pathophysiology of this disease, including the roles played by both ADAMTS13 and the von Willebrand factor (VWF). Much of this work has contributed greatly to our understanding of how these molecules function in “normal” physiology and hemostasis as well. In this chapter we will review the discovery of ADAMTS13 and its role in TTP, recent findings regarding the regulation of ADAMTS13 activity and its interaction with VWF, and the implication of these findings to von Willebrand disease.