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. DATA SOURCES: The information reviewed here was taken from the primary literature, including recent abstracts. STUDY SELECTION: 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. DATA EXTRACTION AND SYNTHESIS: 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.