Drotrecogin alfa (activated): a novel therapeutic strategy for severe sepsis.
Recent studies have highlighted the close link between activation of the coagulation system and the inflammatory response in the pathophysiology of severe sepsis. The protein C anticoagulant pathway plays an integral part in modulating the coagulation and inflammatory responses to infection. In patients with sepsis, endogenous protein C levels are decreased, shifting the balance toward greater systemic inflammation, coagulation, and cell death. On the basis of a single large randomised phase 3 trial, drotrecogin alfa (activated), a recombinant form of human activated protein C, was recently approved for the treatment of adult patients with severe sepsis and a high risk of death. Since its approval, several questions have been raised regarding the appropriate use of this agent. Given the increased risk of serious bleeding and the high cost of treatment, drotrecogin alfa (activated) should be reserved at this time for the most acutely ill patients with severe sepsis who meet the criteria that were used in the phase 3 trial.
Pastores
S M
SM
Department of Anesthesiology and Critical Care Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. pastores@mskcc.org
D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001777:Blood Coagulation; D002986:Clinical Trials as Topic; D006801:Humans; D011486:Protein C / Q000502:physiology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D018805:Sepsis / Q000097:blood / Q000188:drug therapy*
D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated