Coagulation inhibition for sepsis.
Following on the heels of multiple failed clinical trials of adjunctive therapeutic agents in sepsis, the positive outcome of a recent phase III study using activated protein C (APC) has led to a renewed optimism in targeted biotherapies for this syndrome. A growing body of data (both preclinical and clinical) suggests that the protection against death afforded by APC cannot be solely explained by its antithrombotic activity but rather is likely explained by its associated anti-inflammatory and profibrinolytic effects. Although a recent phase III study failed to demonstrate any protective effect of another important antithrombotic molecule, antithrombin, it is premature to conclude that the benefit observed with APC is unique among inhibitors of the coagulation system. The result of a third phase III study examining the effect of tissue factor pathway inhibitor (TFPI) in sepsis is currently awaited, and the possibility that other antithrombotic agents--and combinations thereof--have a place in the therapeutic armamentarium will undoubtedly be the topic of future studies.
Key
Nigel S
NS
Department of Medicine, University of Minnesota Medical School, 480 Mayo Building, 420 Delaware St SE, Minneapolis, MN 55455, USA. keyxx001@umn.edu
Ely
E Wesley
EW
D000925:Anticoagulants / Q000627:therapeutic use*; D019774:Blood Coagulation Factor Inhibitors / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007111:Immunity, Cellular; D018836:Inflammation Mediators / Q000276:immunology / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000209:etiology
D000925:Anticoagulants; D019774:Blood Coagulation Factor Inhibitors; D018836:Inflammation Mediators