Sepsis is an uncontrolled, unregulated and self-sustaining intravascular inflammation that results from an imbalance between proinflammatory reaction and excessive anti-inflammatory response. It is associated with increased mortality and morbidity. The major cause of death is multiple end-organ failure that occurs secondary to disseminated intravascular coagulation. Activated protein C has anti-inflammatory, anticoagulant, and fibrinolytic activity and demonstrated a beneficial effect in reducing mortality in patients with severe sepsis. In this review, the authors evaluated the role of Activated Protein C in sepsis.
StevenL.Sepsis: Menu of new approaches replaces one therapy for all.Cleav Clin J Med.2002; 69(1): 65–73.
2.
BrandtzaegP., SandsetP.M., JooG.B.The quantitative association of plasma endotoxin, antithrombin, protein C, extrinsic inhibitors, and fibrinopeptide A in system menongococcal disease.Thromb Res.1989; 55: 459–70.
3.
FourrierF., ChopinC., GoudemandJ.Septic shock, multiple organ failure, and disseminated intravascular coagulation: Compared patterns of antithrombin III, protein C and protein S deficiencies.Chest.1992; 101: 816–23.
4.
BalkR.A.Severe sepsis and septic shock. Definitions, epidemiology and clinical manifestations.Crit Care Clin.2000; 16: 179–92.
5.
WheelerA.P., BernardG.R.Treating patients with severe sepsis.N Engl J Med.1999; 340: 207–14.
6.
Rangel-FraustoM.S., PittetD., CostiganM.The natural history of the systemic inflammatory response syndrome (SIRS). A retrospective study.JAMA.1995; 273: 117–23.
7.
KanjiS., DevlinJ., PiekosK.Recombinant human activated protein C, drotrecogin alfa (activated): A novel therapy for severe sepsis.Pharmacotherapy.2001; 21(11): 1389–402.
8.
WenzelR.P., PinskyM.R., UlevitchR.J.Current understanding of sepsis.Clin Infect Dis.1996; 22: 407–13.
9.
LeviM., De JongeE., Vander PollT.Rationale for restoration of physiological anticoagulant pathways in patients with sepsis and disseminated intravascular coagulation.Crit Care Med.2001; 29(suppl 1): S90–4.
10.
JongeE., PollT., KeseciogluJ.Anticoagulant factor concentrates in disseminated intravascular coagulation: Rationale for use and clinical experience.Thromb Hemo.2001; 27(6): 667–75.
11.
TaylorF., ChangC., EsmonC.Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon.J Clin Invest.1987; 79: 918–25.
12.
YanS., HelterbrandJ., HartmanD.Low levels of protein C are associated with poor outcome in severe sepsis.Chest.2001; 120: 915–22.
13.
MestersR., HelterbrandJ., UtterbackB.Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications.Crit Care Med.2000; 28: 2209–16.
14.
WhiteB., LivingstoneW., MurphyC.An open-label study of the role of adjuvant hemostatic support with protein C replacement therapy in purpura fulminans associated meningococcemia.Blood.2000; 96: 3719–24.
15.
BernardG., VincentJ., HelterbrandJ.Efficacy and safety of recombinant human activated protein C for severe sepsis.N Engl J Med.2001; 344: 699–709.
16.
BernardG., HelterbrandJ.Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis.Crit Care Med.2001; 29: 2051–9.
17.
HealyD.P.New and emerging therapies for sepsis.Ann Pharmacother.2002; 36: 648–54.
18.
RiedemannN.C., GuoR.F., WardP.A.Novel strategies for the treatment of sepsis.Nat Med.2003; 9(5): 517–24.
19.
GiroirB.P.Recombinant human activated protein C for the treatment of severe sepsis: Is there a role in pediatrics?Pediatr.2003; 15: 92–6.
20.
Activated protein C (Xigris) for severe sepsis.Med Lett.2002; 44(1124): 17–8.
21.
AngusD.C., Linde-ZwirbleW.T., ClermontG.Cost effectiveness of drotrecogin alfa activated (Xigris) in severe sepsis [abstract].Crit Care Med.2002; 30: 492.
22.
ClermontG., Linde-ZwirbleW.T., Van HoutB.A.The effect of recombinant human activated protein C on hospital costs and resource use in severe sepsis [absract].Am J Respir Crit Care Med.2001; 163: A802.
23.
MannsB.J., LeeH., DoigC.J.AN economic evaluation of activated protein C treatment for severe sepsis.N Engl J Med.2002; 347: 993–1000.
