Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure*
- 1 October 2007
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Critical Care Medicine
- Vol. 35 (10), 2375-2382
- https://doi.org/10.1097/01.ccm.0000284508.05247.b3
Abstract
The inability to regulate the inflammatory response initiated upon infection leads to severe sepsis, characterized by widespread microvascular injury and thrombosis, organ ischemia, and dysfunction. A disintegrin-like and metalloprotease with thrombospondin type 1 repeats (ADAMTS)-13 regulates primary hemostasis by proteolyzing von Willebrand factor (VWF). Decreased ADAMTS-13 has been reported in disseminated intravascular coagulation due to severe sepsis. The present study investigates whether the sepsis-related dysregulation of endothelial activation leads to specific changes of ADAMTS-13. Case-control study. Adult intensive care unit in a university hospital. Three groups were studied: a case group of 30 patients with severe sepsis, a control group of 29 patients with comparable organ failure unrelated to sepsis, and 30 age- and gender-matched healthy subjects. None. Significantly lower ADAMTS-13 activity was observed in patients with severe sepsis (43.2%; interquartile range, 32.7, 67.0) than in patients with organ failure unrelated to sepsis (67.8%; 57.4, 87.9; p p We observed low ADAMTS-13 activity and antigen in severe sepsis and in other conditions associated with organ dysfunction. ADAMTS-13 levels were significantly associated with differences in morbidity, mortality, and variables of inflammation and endothelial dysregulation only in severe sepsis patients. This suggests that ADAMTS-13 deficiency may have a pathophysiological relevance specific to severe sepsis.Keywords
This publication has 41 references indexed in Scilit:
- Changes in ADAMTS13 (von-Willebrand-factor-cleaving protease) activity after induced release of von Willebrand factor during acute systemic inflammationThrombosis and Haemostasis, 2005
- Significance of Von Willebrand Factor in Septic and Nonseptic Patients with Acute Lung InjuryAmerican Journal of Respiratory and Critical Care Medicine, 2004
- Von Willebrand factor, platelets and endothelial cell interactionsJournal of Thrombosis and Haemostasis, 2003
- The role of the endothelium in severe sepsis and multiple organ dysfunction syndromeBlood, 2003
- ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditionsBlood, 2002
- Changes in health and disease of the metalloprotease that cleaves von Willebrand factorBlood, 2001
- Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpuraNature, 2001
- Immunoneutralization of Glycoprotein Ibα Attenuates Endotoxin-Induced Interactions of Platelets and Leukocytes With Rat Venular Endothelium In VivoCirculation Research, 2000
- Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in SepsisChest, 1992
- Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome.JCI Insight, 1990