Relationship between the inflammation and coagulation pathways in patients with severe sepsis: implications for therapy with activated protein C.
In patients with severe sepsis, thrombin has been implicated in the interrelationship between the coagulation and inflammation pathways. Thrombin is responsible for conversion of fibrinogen to fibrin (thrombus formation). Thrombin also activates endothelial cells, white blood cells and platelets. Regulation of both the coagulation and inflammation pathways is in part through the interaction of thrombin and activated protein C. Activated protein C has particular attributes that may inhibit microvascular thrombi, promote fibrinolysis and directly dampen the pro-inflammatory aspect of infection. In patients with severe sepsis, many investigators have demonstrated an active coagulopathic state, with low protein C levels. A phase III clinical trial has now demonstrated reduced mortality in patients with severe sepsis receiving activated protein C.
Morris
Peter E
PE
Division of Pulmonary and Critical Care Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina 27104, USA. pemorris@wubmc.edu
Hite
R Duncan
RD
Ohl
Christopher
C
D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D016905:Gram-Negative Bacterial Infections / Q000150:complications; D016908:Gram-Positive Bacterial Infections / Q000150:complications; D006801:Humans; D007249:Inflammation / Q000097:blood; D008833:Microcirculation; D010272:Parasitic Diseases / Q000150:complications; D011486:Protein C / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D013927:Thrombosis / Q000209:etiology
D000925:Anticoagulants; D011486:Protein C