title: Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure.
abstract: Deficiency of ADAMTS13 is found in patients with thrombotic thrombocytopenic purpura (TTP), and the genetic defects in the ADAMTS13 gene or the autoantibody against ADAMTS13 is thought to be responsible for the development of TTP. The clinical correlation and mechanisms of secondary ADAMTS13 deficiency in other disease states were investigated. In addition to TTP, ADAMTS13 levels were severely decreased in patients with sepsis-induced disseminated intravascular coagulation (DIC). The incidence of acute renal failure and serum creatinine levels in patients with ADAMTS13 activity levels lower than 20% (incidence, 41.2%; creatinine, 160 +/- 150 microM [1.81 +/- 1.70 mg/dL]) (P < .05) were significantly higher than they were in patients with ADAMTS13 activity levels higher than 20% (incidence, 15.4%; creatinine, 84 +/- 67 microM [0.95 +/- 0.76 mg/dL]) (P < .01). Additionally, unusually large von Willebrand factor multimers were detected in 26 (51.0%) of 51 patients with ADAMTS13 activity levels lower than 20%. Lower molecular weight forms of ADAMTS13 were found in the plasma of patients with sepsis-induced DIC, suggesting that the deficiency of ADAMTS13 was partially caused by its cleavage by proteases in addition to decreased synthesis in the liver. These data suggested that severe secondary ADAMTS13 deficiency can be associated with sepsis-induced DIC and may contribute to the development of renal failure.
authors.affiliation: Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, 3311-1 Yakushiji, Tochigi-ken 329-0498, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ono
authors.forename: Jun
authors.initials: J
authors.lastname: Mimuro
authors.forename: Seiji
authors.initials: S
authors.lastname: Madoiwa
authors.forename: Kenji
authors.initials: K
authors.lastname: Soejima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kashiwakura
authors.forename: Akira
authors.initials: A
authors.lastname: Ishiwata
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takano
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ohmori
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000172:deficiency*; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004211:Disseminated Intravascular Coagulation / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006463:Hemolytic-Uremic Syndrome; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018805:Sepsis / Q000150:complications* / Q000378:metabolism*; D014841:von Willebrand Factor / Q000235:genetics
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human