Measurement of ADAMTS13 activity and inhibitors

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Abstract
Acquired or congenital deficiency in the plasma von Willebrand factor-cleaving protease ADAMTS13 causes life-threatening thrombotic thrombocytopenic purpura. This condition is characterized primarily by thrombocytopenia and microangiopathic hemolytic anemia, accompanied by variable degrees of neurologic dysfunction, renal failure, and fever. Measurement of ADAMTS13 activity is important in the diagnosis of microangiopathies such as thrombotic thrombocytopenic purpura. This review introduces both established and emerging assays for ADAMTS13 activity, focusing on their impact on clinical practice. Previously established assays are useful screening methods to identify suspected thrombotic thrombocytopenic purpura. Novel assays measuring ADAMTS13 activity using either recombinant peptides or synthetic substrates directly measure the activity quantitatively. These assays can also detect neutralizing autoantibodies in the plasma of patients with acquired ADAMTS13 deficiency. Although ADAMTS13 in control subjects exhibits a broad variation in activity, ranging from 30 to 200%, significant decreases in ADAMTS13 activity have been observed in several physiologic and pathologic conditions. A portion of thrombotic thrombocytopenic purpura patients, however, did not display severe ADAMTS13 deficiency, suggesting that as-yet-unidentified environmental or genetic factors may contribute to the etiology of thrombotic thrombocytopenic purpura. New assays measuring ADAMTS13 activity will contribute significantly to the accurate diagnosis of microangiopathies, ultimately leading to improved clinical treatment of these diseases. These assays may also help to clarify the role of ADAMTS13 activity in additional thrombotic disorders, including disseminated intravascular coagulation, stroke, and myocardial infarction.