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Endogenous Activated Protein C may work to reestablish homeostasis in patients with severe sepsis. This results when this protein modulates coagulation and inflammation and restores fibrinolysis in these patients.

Endogenous Activated Protein C has antiinflammatory properties. These include indirect inhibition of thrombin-mediated inflammatory activity, as well as direct suppression of inflammatory cytokine production and neutrophil activation and adhesion. For example, Activated Protein C has been shown to limit the production of TNF-a and IL-1, interfere with the interaction between lipopolysaccharide and the monocyte CD14 receptor, and decrease E-selectin-mediated inflammation.

Endogenous Activated Protein C also has profibrinolytic properties. These include inhibition of thrombin production and thrombin-mediated inflammation, inhibition of PAI-1 release and TAFI activation, and improvement of the actions of t-PA on fibrin clots.

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Kidokoro A, Iba T, Fukunaga M, et al. Alterations in coagulation and fibrinolysis during sepsis. Shock. 1996;5:223-8.

Vervloet MG, Thijs LG, Hack CE. Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock. Semin Thromb Hemost. 1998;24: 33-44.