ADAMTS13, von Willebrand factor specific cleaving protease

作者：Veyradier Agnes^*; Coppo Paul

来源：Medecine Sciences, 2011, 27(12): 1097-1105.

DOI：10.1051/medsci/20112712016

ADAMTS13, von Willebrand factor specific cleaving protease
ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats) is the specific von Willebrand factor (VWF)-cleaving protease. ADAMTS13 was partially purified from human plasma in 1996 and its gene was cloned in 2001. In case of vascular injury, multimeric VWF is the mediator of both platelet adhesion to the sub-endothelium and platelet aggregation within the microvessels at high shear rates of blood flow. ADAMTS13 regulates VWF adhesive capacity by reducing the size of VWF multimers. A severe functional deficiency of ADAMTS13 (activity lower than 10%) is associated with most cases of thrombotic thrombocytopenic purpura (TIP), a thrombotic microangiopathy characterized by the spontaneous formation, within the microcirculation, of VWF-rich platelet thrombi responsible for a mechanical hemolytic anemia, a consumption thrombocytopenia and a multivisceral ishemia. TIP is a rare disease (4 cases/10(6)/year) with a life-threatening prognosis in the absence of an appropriate treatment in emergency (plasmatherapy). In 90% of cases, TIP is acquired and related to the development of auto-antibodies to ADAMTS13. In the other cases, TIP is inherited via bi-allelic autosomic recessive mutations of ADAMTS13 gene (Upshaw-Schulman syndrome). A better characterization of ADAMTS13 structure/function combined to clinical trials led in TIP patients is crucial to evaluate the relevance of either a plasma-purified or a recombinant ADAMTS13 as a therapeutic agent.

• 出版日期2011-12