Drotrecogin alfa was introduced in the US as a new intravenous treatment for the
reduction of mortality in adult patients with severe sepsis associated with acute organ
dysfunction. Drotrecogin aifa is the first recombinant activated protein C expressed in
human kidney 293 cells. Activated protein C1 an endogenous serine protease, acts as an
antithrombotic via inhibition of factor Va and Vllla, promotes fibrinolysis via inactivation of
plasminogen-activator inhibitor-1 and exerts an anti-inflammatory effect by inhibiting the
production of inflammatory cytokines (tumor necrosis factor-alpha, interieukin-1 and 6) by
monocytes. It was shown that the majority of patients with sepsis have reduced levels of
activated protein C. In a baboon model of lethal E. coli sepsis, administration of activated
protein C reduced mortality. In a phase III clinical trial, intravenous infusion of drotrecogin
alfa at a dose of 24 μg/kg/h over 96 h significantly reduced the risk of death compared with
placebo in patients with severe sepsis. However, an increased risk of serious bleeding has
been associated with the administration of the drug.
