Description
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 C
1 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.
Uses
Protein C from human plasma has been used for pre-treatment of endothelial cells prior to antibody-inhibition assay. It has also been used in activated protein C (APC) assay to determine its inhibitory effect on copper.
General Description
Protein C from human plasma is encoded by the gene PROC. In human chromosome, the gene is localised on chromosome 2q14. Activated protein C (APC) cleaves protease activated receptor 1 (PAR1) resulting in cytoprotective and anti-inflammatory effects. Clinical trials with APC implicates its use in treating severe early onset preeclampsia in pregnant women and prolongs pregnancy and helps in perinatal outcomes.
Biochem/physiol Actions
Adenomatous Polyposis Coli (APC) has a key role in the proteasome-mediated degradation of β-catenin. APC mutations cause accumulation of β-catenin in the nucleus leading to activation of LEF-1 and/or TCF, and the induction of target genes such as the oncogene c-myc. It is involved in regulation of mitotic chromosome separation and stability.
