Tissue factor inhibition and clinical trial results of tissue factor pathway inhibitor in sepsis.
Tissue factor mediated pathways leading to microvascular thromboses and endothelial activation appear to play an important role in the development of multiple organ failure associated with severe sepsis. Tissue factor pathway inhibitor (TFPI) is an endogenous inhibitor of tissue factor associated coagulation cascades. In experimental models of severe sepsis, treatment with TFPI results in significant reduction in mortality. Similarly, a recently completed Phase II 210-patient study comparing placebo and infusions of TFPI showed trends toward a relative reduction in day 28 all-cause mortality in TFPI treated patients. These data suggest that coagulation cascades involving tissue factor contribute to organ dysfunction in critically ill septic patients. TFPI may be a useful therapy in improving outcome of severe sepsis.
Abraham
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Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver 80220-3700, USA.
D000818:Animals; D002986:Clinical Trials as Topic; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy; D008074:Lipoproteins / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy*; D013925:Thromboplastin / Q000037:antagonists & inhibitors*
D008074:Lipoproteins; D011994:Recombinant Proteins; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin