Mechanisms of recombinant activated protein C in sepsis

Activation of the coagulation system and inflammatory cytokines are universal in sepsis and are interrelated. Although activated protein C works on both pathways its actions on the inflammatory cascade are less well understood.

Activation of coagulation occurs along a spectrum ranging through asymptomatic laboratory abnormalities, micro thrombosis and overt DIC with diffuse bleeding. In general the more severe the coagulation disturbance the more the patient benefits from activated protein C up to the point where the coagulopathy increases bleeding risk. That point is difficult to define, contributing to difficulty in patient selection. These issues are discussed in a review of the mechanisms of activated protein C, part of a supplement in the journal Critical Care.