The protein C pathway.
OBJECTIVE
To examine the role of the protein C anticoagulant pathway in the regulation of microvascular thrombosis. The mechanisms by which inflammation impairs the function of this pathway are also reviewed; conversely, we will survey emerging knowledge of the multiple mechanisms by which the protein C anticoagulant pathway can control the inflammatory response.


METHODS
The information reviewed here was taken from the primary literature, including recent abstracts.


METHODS
All studies that bear directly on the interrelationship between the protein C anticoagulant pathway and inflammation were included, as was a summary of the initial clinical experience with protein C/activated protein C therapy in sepsis.


METHODS
The results from each of the experimental approaches are summarized. Clinical experience with protein C supplementation in sepsis, although promising, is still in the early stages of study.


CONCLUSIONS
The protein C anticoagulant pathway is a major mechanism in controlling microvascular thrombosis. Protein C deficiency that can occur in sepsis facilitates thrombin generation in the microvasculature, probably augmenting inflammatory responses and contributing to endothelial cell dysfunction. Animal studies and preliminary clinical results suggest that protein C/activated protein C supplementation may be useful in reversing microvascular dysfunction.
Esmon
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Oklahoma Medical Research Foundation, Oklahoma City 73104, USA. charles-esmon@omrf.ouhsc.edu
D000818:Animals; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D011486:Protein C / Q000502:physiology*; D018805:Sepsis / Q000188:drug therapy; D013927:Thrombosis / Q000188:drug therapy
D011486:Protein C