Von Willebrand Factor — A New Target for TTP Treatment?

Abstract

Thrombotic thrombocytopenic purpura (TTP), a rare thrombotic microangiopathy, is defined by a mechanical hemolytic anemia, severe thrombocytopenia, and visceral ischemia due to systemic platelet-rich microthrombi. Specifically in TTP microthrombi, von Willebrand factor, not fibrinogen, is the protein that binds to platelets.¹ Von Willebrand factor is a multimeric glycoprotein that is crucial for physiologic platelet adhesion and aggregation at high shear rates of blood flow, and the largest von Willebrand factor multimers are the most adhesive. The hemostatic power of von Willebrand factor is regulated by a specific cleaving metalloprotease named ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13). Since 1998, the link between TTP, von Willebrand factor, and ADAMTS13 has been elucidated^2-5: a severe functional deficiency of ADAMTS13 (due mainly to anti-ADAMTS13 autoantibodies and very rarely to ADAMTS13 gene mutations) causes the accumulation of platelet-hyperadhesive, ultralarge von Willebrand factor multimers in the blood, spontaneously inducing the formation of microthrombi in the microvasculature.