Drotrecogin alfa (activated): a novel therapeutic strategy for severe sepsis
- Department of Anesthesiology and Critical Care Medicine, Memorial Sloan-Kettering Cancer Center, New York, and Weill Medical College of Cornell University, New York
- Correspondence and reprint requests to: Dr Stephen M Pastores, Department of Anesthesiology and Critical Care Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue M-210 New York, NY 10021, USA; pastores{at}mskcc.org
- Received 25 June 2002
- Accepted 14 October 2002
Abstract
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.
- activated protein C
- sepsis
- drotrecogin alfa (activated)
- inflammation
- coagulation
- multiorgan failure
- bleeding
- APACHE II, Acute Physiology and Chronic Health Evaluation II (score)
- HSCT, haematopoietic stem cell transplantation
- PAI-1, plasminogen activator inhibitor-1
- TFPI
- tissue factor pathway inhibitor
- TNF-α, tumour necrosis factor-α
