[Activated protein C, coagulation, inflammation, and treatment of severe sepsis].
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.
van Deventer
S J
SJ
Afd. Maag-, Darm- en Leverziekten, Academisch Medisch Centrum, Postbus 22.660, 1100 DD Amsterdam. s.j.vandeventer@amc.uva.nl
Pajkrt
D
D
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D011486:Protein C / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D015850:Interleukin-6; D011486:Protein C; D011994:Recombinant Proteins; C036309:fibrin fragment D