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

(2007) CRITICAL CARE MEDICINE. 35(10). p.2375-2382
Author
Organization
Abstract
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-1 3 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 11 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.
Keywords
severe sepsis, thrombosis, ADAMTS-13, von Willebrand factor, VON-WILLEBRAND-FACTOR, THROMBOTIC THROMBOCYTOPENIC PURPURA, FACTOR-CLEAVING PROTEASE, DISSEMINATED INTRAVASCULAR COAGULATION, ACUTE LUNG INJURY, ENDOTHELIAL-CELLS, FACTOR MULTIMERS, STELLATE CELLS, RENAL-FAILURE, DISEASE

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MLA
Martin, Kenneth, Delphine Borgel, Nicolas Lerolle, et al. “Decreased ADAMTS-13 (A Disintegrin-like and Metalloprotease with Thrombospondin Type 1 Repeats) Is Associated with a Poor Prognosis in Sepsis-induced Organ Failure.” CRITICAL CARE MEDICINE 35.10 (2007): 2375–2382. Print.
APA
Martin, Kenneth, Borgel, D., Lerolle, N., Feys, H., Trinquart, L., Vanhoorelbeke, K., Deckmyn, H., et al. (2007). Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure. CRITICAL CARE MEDICINE, 35(10), 2375–2382.
Chicago author-date
Martin, Kenneth, Delphine Borgel, Nicolas Lerolle, Hendrik Feys, Ludovic Trinquart, Karen Vanhoorelbeke, Hans Deckmyn, Paulette Legendre, Jean-Luc Diehl, and Dominique Baruch. 2007. “Decreased ADAMTS-13 (A Disintegrin-like and Metalloprotease with Thrombospondin Type 1 Repeats) Is Associated with a Poor Prognosis in Sepsis-induced Organ Failure.” Critical Care Medicine 35 (10): 2375–2382.
Chicago author-date (all authors)
Martin, Kenneth, Delphine Borgel, Nicolas Lerolle, Hendrik Feys, Ludovic Trinquart, Karen Vanhoorelbeke, Hans Deckmyn, Paulette Legendre, Jean-Luc Diehl, and Dominique Baruch. 2007. “Decreased ADAMTS-13 (A Disintegrin-like and Metalloprotease with Thrombospondin Type 1 Repeats) Is Associated with a Poor Prognosis in Sepsis-induced Organ Failure.” Critical Care Medicine 35 (10): 2375–2382.
Vancouver
1.
Martin K, Borgel D, Lerolle N, Feys H, Trinquart L, Vanhoorelbeke K, et al. Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure. CRITICAL CARE MEDICINE. 2007;35(10):2375–82.
IEEE
[1]
K. Martin et al., “Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure,” CRITICAL CARE MEDICINE, vol. 35, no. 10, pp. 2375–2382, 2007.
@article{8549113,
  abstract     = {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-1 3 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 11 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.},
  author       = {Martin, Kenneth and Borgel, Delphine and Lerolle, Nicolas and Feys, Hendrik and Trinquart, Ludovic and Vanhoorelbeke, Karen and Deckmyn, Hans and Legendre, Paulette and Diehl, Jean-Luc and Baruch, Dominique},
  issn         = {0090-3493},
  journal      = {CRITICAL CARE MEDICINE},
  keywords     = {severe sepsis,thrombosis,ADAMTS-13,von Willebrand factor,VON-WILLEBRAND-FACTOR,THROMBOTIC THROMBOCYTOPENIC PURPURA,FACTOR-CLEAVING PROTEASE,DISSEMINATED INTRAVASCULAR COAGULATION,ACUTE LUNG INJURY,ENDOTHELIAL-CELLS,FACTOR MULTIMERS,STELLATE CELLS,RENAL-FAILURE,DISEASE},
  language     = {eng},
  number       = {10},
  pages        = {2375--2382},
  title        = {Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure},
  url          = {http://dx.doi.org/10.1097/01.CCM.0000284508.05247.B3},
  volume       = {35},
  year         = {2007},
}

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