ADAMTS13 assays and ADAMTS13-deficient mice

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Abstract
Thrombotic thrombocytopenic purpura can be induced by acquired or congenital deficiency of the plasma von Willebrand factor-cleaving protease, ADAMTS13. Measurement of ADAMTS13 activity is important for the diagnosis and treatment of microangiopathies including thrombotic thrombocytopenic purpura. Phenotypic analysis of mice lacking the Adamts13 gene is valuable for understanding the pathogenesis of microangiopathies. The minimum substrate for ADAMTS13 activity was identified as 73 amino acid residues in the A2 domain of von Willebrand factor, called VWF73. Several new assays have been developed using this sequence. The VWF73-based assays are rapid, quantitative, and easy to handle, and are well correlated with the measures from previous assays. Mice lacking the Adamts13 gene were produced. The mice were viable and fertile. They showed a prothrombotic state but no symptoms of spontaneous thrombocytopenia, hemolytic anemia, or microvascular thrombosis were observed. VWF73-based ADAMTS13 assays will significantly facilitate the accurate diagnosis of microangiopathies and contribute to the improved clinical treatment of these diseases. Accumulated clinical information on patients with ADAMTS13 deficiency and mice lacking the Adamts13 gene indicates that additional environmental or genetic susceptibility factors are required to trigger thrombotic thrombocytopenic purpura.