Deficiency of ADAMTS13 and thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura, characterized by the presence of systemic hyaline thrombi in the arterioles and capillaries, is a potentially fatal disease that responds to plasma infusion or exchange. Recent studies have demonstrated that a metalloprotease in the normal plasma cleaves endothelial von Willebrand factor to a series of multimers. A deficiency of the protease, due to autoimmune IgG inhibitors or genetic mutations, is detected in patients with thrombotic thrombocytopenic purpura. 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 thrombotic thrombocytopenic purpura. In the circulation, proteolysis of von Willebrand factor is critical in regulating vWF-platelet interaction. These advances in knowledge provide the basis for a rational approach to improving the diagnosis and treatment of thrombotic thrombocytopenic purpura.