title: ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura.
abstract: Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized in the liver, and its main function is to cleave von Willebrand factor (VWF) anchored on the endothelial surface, in circulation, and at the sites of vascular injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly reduced (>20%) in other forms of thrombotic microangiopathy secondary to hematopoietic progenitor cell transplantation, infection, and disseminated malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains the initial treatment of choice to date, but novel therapeutics such as recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13 deficiency has been shown to be a risk factor for the development of myocardial infarction, stroke, cerebral malaria, and preeclampsia.
authors.affiliation: Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104; email: zheng@email.chop.edu.
authors.forename: X Long
authors.initials: XL
authors.lastname: Zheng
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000276:immunology; D000071120:ADAMTS13 Protein; D001323:Autoantibodies / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009154:Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D011994:Recombinant Proteins / Q000627:therapeutic use; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: arterial thrombosis; autoantibodies; autoimmune disorder; metalloprotease; mutations; rare hematological disease