Activated protein C in sepsis: a critical review.

Abstract

PURPOSE OF REVIEW:

An impaired function of the protein C pathway plays a central role in the pathogenesis of sepsis. Administration of human recombinant activated protein C (Xigris) may restore the dysfunctional anticoagulant mechanism and may simultaneously modulate the pro-inflammatory response. Initial clinical studies with activated protein C in patients with sepsis showed a reduction of 28-day mortality. However, subsequent studies did cast some doubt on the efficacy and also the safety of this treatment.

RECENT FINDINGS:

A number of randomized controlled clinical studies confirm beneficial effects of activated protein C in patients with severe sepsis. Aggregate analyses, however, have cast some doubt on the usefulness of treatment with activated protein C. In some clinical situations, such as patients with a relatively low disease severity and pediatric patients, activated protein C was shown not to be effective. Activated protein C seems to increase the risk of (severe) bleeding, although the absolute risk is low in patients that were included in clinical trials.

SUMMARY:

Clinical studies support the use of activated protein C in patients with severe sepsis; however, in view of the substantial skepticism surrounding the efficacy and safety of this treatment, additional placebo-controlled data are required.

• Authors: Marcel Levi
• Journal: Current opinion in hematology (Curr Opin Hematol) Vol. 15 Issue 5 Pg. 481-6 (Sep 2008) ISSN: 1531-7048 [Electronic] United States
• PMID: 18695371 (Publication Type: Journal Article, Review)

Chemical References

• Protein C
• Recombinant Proteins
• drotrecogin alfa activated

Topics

• Hemorrhage (chemically induced)
• Humans
• Protein C (adverse effects, therapeutic use)
• Recombinant Proteins (adverse effects, therapeutic use)
• Sepsis (drug therapy)
• Treatment Failure
• Treatment Outcome