Pharmacological inhibition of tissue factor.
Tissue factor plays an essential role in the initiation of coagulation in vivo. In severe conditions, including sepsis and acute lung injury, increased expression of tissue factor may induce disseminated intravascular coagulation and fibrin deposition in organs, which are believed to have a determining impact on patient outcome. Tissue factor also acts as a signaling receptor and is involved in the systemic inflammatory response, as in cancer progression and atherosclerosis. Interventions aiming at limiting tissue factor activities have been evaluated in multiple experimental studies and the observed results have supported the potential benefits for coagulation disorders, inflammation, and survival. The effects of the main physiological inhibitor of tissue factor, tissue factor pathway inhibitor, have been evaluated in two large clinical trials in sepsis. Even though they are not associated with an improved outcome, the observed data support further clinical studies.
Laterre
Pierre-Francois
PF
Department of Critical Care Medicine, St. Luc University Hospital, Université Catholigue de Louvan, Brussels, Belgium. laterre@rean.ucl.ac.be
Wittebole
Xavier
X
Collienne
Christine
C
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000401:mortality; D008074:Lipoproteins / Q000378:metabolism / Q000627:therapeutic use*; D008168:Lung / Q000378:metabolism; D055370:Lung Injury; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005337:Fibrin; D013925:Thromboplastin