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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), pp. 408-416. (doi:10.1056/NEJM200108093450603).

Record type: Article

Abstract

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.

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Published date: 9 August 2001

Identifiers

Local EPrints ID: 40616
URI: http://eprints.soton.ac.uk/id/eprint/40616
PURE UUID: 62dd6e21-ef29-45b8-a02b-d8254f08f57a
ORCID for Saul N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 07 Jul 2006
Last modified: 17 Jul 2017 15:33

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Contributors

Author: Saul N. Faust ORCID iD
Author: Michael Levin
Author: Odile B. Harrison
Author: Robert D. Goldin
Author: Marion S. Lockhart
Author: Sheila Kondaveeti
Author: Zoltan Laszik
Author: Charles T. Esmon
Author: Robert S. Heyderman

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