Dysfunction of endothelial protein C activation in severe meningococcal sepsis

Faust, Saul N., Levin, Michael, Harrison, Odile B., Goldin, Robert D., Lockhart, Marion S., Kondaveeti, Sheila, Laszik, Zoltan, Esmon, Charles T. and Heyderman, Robert S. (2001) Dysfunction of endothelial protein C activation in severe meningococcal sepsis. New England Journal of Medicine, 345, (6), 408-416. (doi:10.1056/NEJM200108093450603).


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Background: Impairment of the protein C anticoagulation pathway is critical to the thrombosis associated with sepsis and to the development of purpura fulminans in meningococcemia. We studied the expression of thrombomodulin and the endothelial protein C receptor in the dermal microvasculature of children with severe meningococcemia and purpuric or petechial lesions.

Methods: We assessed the integrity of the endothelium and the expression of thrombomodulin and the endothelial protein C receptor in biopsy specimens of purpuric lesions from 21 children with meningococcal sepsis (median age, 41 months), as compared with control skin-biopsy specimens.

Results: The expression of endothelial thrombomodulin and of the endothelial protein C receptor was lower in the patients with meningococcal sepsis than in the controls, both in vessels with thrombosis and in vessels without thrombosis. On electron microscopical examination, the endothelial cells were generally intact in both thrombosed and nonthrombosed vessels. Plasma thrombomodulin levels in the children with meningococcal sepsis (median, 6.4 ng per liter) were higher than those in the controls (median, 3.6 ng per liter; P=0.002). Plasma levels of protein C antigen, protein S antigen, and antithrombin antigen were lower than those in the controls. In two patients treated with unactivated protein C concentrate, activated protein C was undetectable at the time of admission, and plasma levels remained low.

Conclusions: In severe meningococcal sepsis, protein C activation is impaired, a finding consistent with down-regulation of the endothelial thrombomodulin–endothelial protein C receptor pathway.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1056/NEJM200108093450603
ISSNs: 0028-4793 (print)
Related URLs:
Subjects: R Medicine > RB Pathology
R Medicine > RJ Pediatrics > RJ101 Child Health. Child health services
Divisions : University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
ePrint ID: 40616
Accepted Date and Publication Date:
9 August 2001Published
Date Deposited: 07 Jul 2006
Last Modified: 31 Mar 2016 12:11
URI: http://eprints.soton.ac.uk/id/eprint/40616

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