ABSTRACT
The protein C pathway plays a critical role in preventing thrombosis, particularly in the
microcirculation. The pathway can be down-regulated by inflammatory mediators, oxidants,
and proteases from leukocytes. The pathway also exhibits anti-inflammatory activity, probably
mediated partly by preventing NFkB nuclear translocation and blocking both leukocyte adhesion and activation. The combined anticoagulant and anti-inflammatory properties of the pathway
make it an attractive candidate for the treatment of acute inflammatory diseases, such as sepsis,
that trigger both a hypercoaguable and hyperinflammatory state. These responses are probably
heightened by the decreased levels of protein C that occur in severe sepsis. Both protein C and
activated protein C supplementation have been used in severe sepsis. The results from a phase III
study of activated protein C seem very promising since it was stopped approximately half way
through the anticipated enrollment because of statistically significant decreases in 28-day all-
cause mortality.
