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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Dysfunction of endothelial protein C activation in severe meningococcal sepsis
New England Journal of Medicine, Volume 345, No. 6, Year 2001
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Description
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. Copyright © 2001 Massachusetts Medical Society.
Authors & Co-Authors
Faust, Saul N.
United Kingdom, London
Imperial College London School of Medicine
Levin, Michael E.
United Kingdom, London
Imperial College London School of Medicine
Harrison, Odile Barbara
United Kingdom, London
Imperial College London School of Medicine
Goldin, Robert David F.
United Kingdom, London
Imperial College London School of Medicine
Esmon, Charles T.
United States, Oklahoma City
Oklahoma Medical Research Foundation
United States, Norman
The University of Oklahoma
United States, Chevy Chase
Howard Hughes Medical Institute
Heyderman, Robert Simon
United Kingdom, Bristol
University of Bristol
Statistics
Citations: 667
Authors: 6
Affiliations: 5
Identifiers
Doi:
10.1056/NEJM200108093450603
ISSN:
00284793
Research Areas
Maternal And Child Health