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  • Title: [Activated protein C, coagulation, inflammation, and treatment of severe sepsis].
    Author: van Deventer SJ, Pajkrt D.
    Journal: Ned Tijdschr Geneeskd; 2001 Mar 31; 145(13):613-6. PubMed ID: 11305209.
    Abstract:
    During the past 20 years several treatments designed to reduce inflammatory responses to sepsis have been unsuccessful. Sepsis results from a generalised inflammatory and procoagulant response to an infection. Activated protein C, a component of the anticoagulant system, is an anti-thrombotic serine protease with anti-inflammatory properties. A recently published study reported the results of a large clinical trial in which recombinant human activated protein C significantly reduced mortality in patients with severe sepsis. Treatment with activated protein C also reduced circulating D-dimer and IL-6 levels, which are markers of coagulation activation and inflammation. There are several reasons why activated protein C could be effective in sepsis. Firstly, reduced levels of protein C are found during sepsis and are associated with an increased risk of death. Secondly, activated protein C can directly inhibit factors Va and VIIIa, resulting in decreased thrombin formation. Finally, activated protein C can reduce plasminogen activator inhibitor I, thereby stimulating fibrinolysis. In addition to these effects on thrombin formation, activated protein C directly reduces pro-inflammatory responses by as yet unknown mechanisms.
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