Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura.

Von Willebrand factor (vWF), a glycoprotein critical for supporting platelet adhesion and aggregation at sites of vessel injury, exists in the plasma as a series of multimers. Recent studies have shown that a metalloprotease cleaves endothelial vWF to a series of multimers. A deficiency of the protease activity due to autoimmune IgG inhibitors or genetic mutations is associated with thrombotic thrombocytopenic purpura (TTP). Positional cloning based on kindreds with a genetic deficiency of the protease and amino acid sequencing of the purified protein have identified the protease as a novel member of the ADAMTS (a disintegrin and metalloprotease with thrombospondin type 1 repeat) zinc metalloprotease family located on the long arm of chromosome 9. Mutations of the gene are detected in patients with the congenital form of TTP. These findings support the view that vWF proteolysis is critical in regulating vWF-platelet interaction and set the stage for improving the diagnosis and treatment of thrombotic thrombocytopenic purpura.