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 M [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 M [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. (Blood. 2006;107: 528-534)

Decreased activity of plasma ADAMTS13 are related to enhanced cytokinemia and endotoxemia in patients with acute liver failure

“…A previous study (13) demonstrated that deficiency of ADAMTS13-associated inflammation promotes UL-VWFM the formation and severe, secondary ADAMTS13 deficiency can be associated with sepsis-induced DIC and may contribute to renal failure development (28), supporting the authors' data and hypothesis.…”

Biomarkers of endothelial dysfunction: can they help us deciphering systemic inflammation and sepsis?

“…The incidence of acute renal failure in patients with decreased ADAMTS13 levels was 41.2%. Decrease of the protein was due to a combination of increased cleavage together with a decreased synthesis of new ADAMTS 13 in the liver (Furlan and Lammle 2001;Mimuro et al 2008;Ono et al 2006). …”

Thrombotic Thrombocytopenic Purpura: A Thrombotic Disorder Caused by ADAMTS13 Deficiency

“…Some studies have reported that ADAMTS13 is also decreased in conditions such as sepsis, disseminated intravascular coagulopathy and liver diseases, occasionally to very low levels [48][49][50]. However, these observations remain controversial [51;52], and the significance of decreased ADAMTS13 levels remains uncertain if they are not accompanied by evidence of decreased VWF proteolysis.…”