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Recombinant human activated protein C in severe sepsis
1Department of Experimental and Clinical Pharmacology, College of Pharmacy, Center for Excellence in Critical Care, University of Minnesota, 308 Harvard Street S.E., Minneapolis, MN 55455, USA. mannx002@umn.edu
Summary
Recombinant human activated protein C (rhAPC), or drotrecogin alfa (activated), significantly reduced mortality in severe sepsis patients. This anticoagulant therapy targets coagulation and inflammation imbalances during critical illness.
Area of Science:
- Biochemistry
- Pharmacology
- Critical Care Medicine
Background:
- Protein C is a vitamin K-dependent serine protease that balances the coagulation cascade.
- Activated protein C (APC) acts as an anticoagulant, fibrinolytic, and anti-inflammatory agent.
- Severe sepsis triggers a procoagulant state, depleting natural APC and leading to organ failure.
Purpose of the Study:
- To describe the role of APC in coagulation, inflammation, and fibrinolysis.
- To review the pharmacology, pharmacokinetics, and clinical trials of recombinant human activated protein C (rhAPC).
- To evaluate the efficacy and safety of drotrecogin alfa (activated) in sepsis.
Main Methods:
- Review of existing literature on protein C and APC.
- Analysis of data from a Phase III safety and efficacy trial of drotrecogin alfa (activated).
- Pharmacological and pharmacokinetic assessment of rhAPC.
Main Results:
- Drotrecogin alfa (activated) demonstrated a significant improvement in mortality compared to placebo (24.7% vs. 30.8%).
- This represents a 6.1% absolute difference and a 19.4% relative risk reduction in mortality.
- Low protein C levels correlate with poor outcomes in severe sepsis.
Conclusions:
- rhAPC (drotrecogin alfa (activated)) is effective in reducing mortality in severe sepsis.
- Careful patient selection and further studies are needed for optimal use.
- Potential modifications in dosing schemes may be beneficial based on patient response.