A disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13 (ADAMTS13) (ADAMTS13)

ADAMTS13, also known as von Willebrand factor-cleaving protease, is a plasma metalloprotease essential for regulating blood clotting by controlling the size of von Willebrand factor (VWF) multimers (UniProt P59510). It specifically cleaves the VWF A2 domain at the Tyr1605-Met1606 peptide bond, a process triggered by shear-induced conformational changes in VWF that expose the cryptic cleavage site (PubMed: 11593434). This regulatory mechanism prevents the accumulation of ultra-large VWF multimers, which are highly prothrombotic and can cause spontaneous platelet aggregation in the microvasculature. Clinical deficiency of ADAMTS13, often due to genetic mutations or acquired autoantibodies, results in thrombotic thrombocytopenic purpura (TTP), a life-threatening condition characterized by microangiopathic hemolytic anemia and widespread microvascular thrombosis (StatPearls: Thrombotic Thrombocytopenic Purpura). Therapeutic interventions focus on restoring ADAMTS13 activity through plasma exchange or recombinant enzyme replacement, such as Adzynma (FDA, 2023). Additionally, agents like caplacizumab target the VWF-platelet axis to mitigate the consequences of impaired VWF processing in the absence of functional ADAMTS13 (N Engl J Med: 380:335-346). Monitoring ADAMTS13 activity and the presence of inhibitors is crucial for the diagnosis and management of microangiopathic disorders.

Other names

von Willebrand factor-cleaving proteaseVWF-CPVWFCPADAM-TS13

Restoration of von Willebrand factor-cleaving activity via enzyme replacement therapy or prevention of VWF-mediated platelet adhesion by blocking the VWF A1 domain.