ADAMTS13
ADAMTS13 is the von Willebrand factor-cleaving protease, a specialty of the family with direct clinical importance. Produced mainly by hepatic stellate cells, it clips the A2 domain of ultra-large von Willebrand factor multimers, preventing spontaneous platelet aggregation. Hereditary or acquired deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura, a life-threatening microangiopathy, and measurement of ADAMTS13 activity is standard in its diagnosis. Recombinant ADAMTS13 has been developed as enzyme-replacement therapy for congenital TTP, and the protein is equally central to thrombosis, hematology and transfusion medicine research. Efficient cleavage requires shear-stress-induced unfolding of the A2 domain, and plasma ADAMTS13 activity measurement is used to distinguish TTP from other thrombotic microangiopathies.
