Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure.

Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure.

MedLine Citation:	PMID: 17944029 Owner: NLM Status: MEDLINE
Abstract/OtherAbstract:	OBJECTIVE: 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. DESIGN: Case-control study. SETTING: Adult intensive care unit in a university hospital. PATIENTS/SUBJECTS: 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. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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 < .05) and healthy subjects (105.6%; 87.2, 125.6; p < .001). Accordingly, ADAMTS-13 antigen was more decreased in patients with severe sepsis than in patients with organ failure unrelated to sepsis and healthy subjects. VWF antigen was higher in patients with severe sepsis than in patients with organ failure unrelated to sepsis and healthy subjects. We found strong negative correlations in severe sepsis but not in organ failure unrelated to sepsis, between ADAMTS-13 activity and 1) VWF antigen; 2) thrombomodulin; 3) interleukin-6; 4) Acute Physiology and Chronic Health Evaluation II score; 5) shock; 6) acute renal injury. Moreover, patients above the median of ADAMTS-13 activity presented a higher survival compared with those below the median in the patients with severe sepsis but not in the patients with organ failure unrelated to sepsis. In contrast, there was no significant association between VWF antigen and survival in either the severe sepsis group or the group with organ failure unrelated to sepsis. CONCLUSIONS: 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.

Authors:	Kenneth Martin; Delphine Borgel; Nicolas Lerolle; Hendrik B Feys; Ludovic Trinquart; Karen Vanhoorelbeke; Hans Deckmyn; Paulette Legendre; Jean-Luc Diehl; Dominique Baruch
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Publication Detail:	Type: Journal Article; Research Support, Non-U.S. Gov't
Journal Detail:	Title: Critical care medicine Volume: 35 ISSN: 0090-3493 ISO Abbreviation: Crit. Care Med. Publication Date: 2007 Oct
Date Detail:	Created Date: 2007-10-17 Completed Date: 2007-11-27 Revised Date: 2008-10-28
Medline Journal Info:	Nlm Unique ID: 0355501 Medline TA: Crit Care Med Country: United States
Other Details:	Languages: eng Pagination: 2375-82 Citation Subset: AIM; IM
Copyright Information:	(C) 2007 Lippincott Williams & Wilkins, Inc.
Affiliation:	INSERM, Unit 765, Paris, France.
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MeSH Terms
Descriptor/Qualifier:	ADAM Proteins / blood* Aged Case-Control Studies Female Humans Male Multiple Organ Failure / etiology, mortality Prognosis Sepsis / blood, complications*, mortality Severity of Illness Index
Chemical
Reg. No./Substance:	EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/ADAMTS13 protein, human
Comments/Corrections
Comment In:	Crit Care Med. 2008 Oct;36(10):2959-60; author reply 2960-1 [PMID: 18812813 ] Crit Care Med. 2007 Oct;35(10):2453-4 [PMID: 17885389 ]

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