title: Therapeutic modulation of coagulation and fibrinolysis in acute lung injury and the acute respiratory distress syndrome.
abstract: Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are characterized by excessive intraalveolar fibrin deposition, driven, at least in part by inflammation. The imbalance between activation of coagulation and inhibition of fibrinolysis in patients with ALI/ARDS favors fibrin formation and appears to occur both systemically and in the lung and airspace. Tissue factor (TF), a key mediator of the activation of coagulation in the lung, has been implicated in the pathogenesis of ALI/ARDS. As such, there have been numerous investigations modulating TF activity in a variety of experimental systems in order to develop new therapeutic strategies for ALI/ARDS. This review will summarize current understanding of the role of TF and other proteins of the coagulation cascade as well the fibrinolysis pathway in the development of ALI/ARDS with an emphasis on the pathways that are potential therapeutic targets. These include the TF inhibitor pathway, the protein C pathway, antithrombin, heparin, and modulation of fibrinolysis through plasminogen activator- 1 (PAI-1) or plasminogen activators (PA). Although experimental studies show promising results, clinical trials to date have proven unsuccessful in improving patient outcomes. Modulation of coagulation and fibrinolysis has complex effects on both hemostasis and inflammatory pathways and further studies are needed to develop new treatment strategies for patients with ALI/ARDS.
authors.affiliation: Department of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, T1218 MCN, 1161 21st Avenue S. Nashville, TN 37232-2650, USA.
authors.forename: Sara C
authors.initials: SC
authors.lastname: Sebag
authors.forename: Julie A
authors.initials: JA
authors.lastname: Bastarache
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D001777:Blood Coagulation / Q000502:physiology*; D015942:Factor VIIa / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D011486:Protein C / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D013925:Thromboplastin / Q000502:physiology
chemical_list: D000991:Antithrombins; D011486:Protein C; D011994:Recombinant Proteins; D006493:Heparin; D013925:Thromboplastin; C103587:recombinant FVIIa; D015942:Factor VIIa