ATVB In Focus Platelet Activation and the Formation of the Platelet Plug Series Editor: Lawrence Brass Deficiency of ADAMTS13 Causes Thrombotic

Abstract—In the circulation, a plasma metalloprotease, ADAMTS13, cleaves von Willebrand factor (vWF) in a shear-dependent manner. This article reviews the role of this cleavage in regulating vWF-platelet interaction and proposes a scheme for understanding how a deficiency of ADAMTS13 results in the development of microthrombi in patients with thrombotic thrombocytopenic purpura. (Arterioscler Thromb Vasc Biol. 2003;23:388-396.) Key Words: von Willebrand factor thrombotic thrombocytopenic purpura ADAMTS13 shear stress von Willebrand factor cleaving protease von Willebrand factor (vWF), a multimeric glycoproteinsynthesized in endothelial cells and megakaryocytes, supports platelet adhesion and aggregation in conditions of high shear stress like those in the arterioles and capillaries. A deficiency in vWF causes bleeding diathesis in patients with von Willebrand disease. Two platelet-surface glycoprotein complexes, Ib/IX/V and IIb3, bind vWF. vWF-platelet binding is minimal in the normal circulation. A lack of interaction between vWF and glycoprotein IIb3 is expected because this receptor normally exists in an inactive form. I