title: Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome.
abstract: Enhanced intrapulmonary fibrin deposition as a result of abnormal broncho-alveolar fibrin turnover is a hallmark of acute respiratory distress syndrome (ARDS), pneumonia and ventilator-induced lung injury (VILI), and is important to the pathogenesis of these conditions. The mechanisms that contribute to alveolar coagulopathy are localized tissue factor-mediated thrombin generation, impaired activity of natural coagulation inhibitors and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. There is an intense and bidirectional interaction between coagulation and inflammatory pathways in the bronchoalveolar compartment. Systemic or local administration of anticoagulant agents (including activated protein C, antithrombin and heparin) and profibrinolytic agents (such as plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical studies show additional anti-inflammatory effects of these therapies in ARDS and pneumonia.
authors.affiliation: Laboratory for Experimental Intensive Care and Anesthesiology, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Glas
authors.forename: K F
authors.initials: KF
authors.lastname: Van Der Sluijs
authors.forename: M J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: J-J H
authors.initials: JJ
authors.lastname: Hofstra
authors.forename: T
authors.initials: T
authors.lastname: Van Der Poll
authors.forename: M
authors.initials: M
authors.lastname: Levi
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D005337:Fibrin / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D011014:Pneumonia / Q000097:blood / Q000276:immunology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D055397:Ventilator-Induced Lung Injury / Q000097:blood* / Q000188:drug therapy / Q000276:immunology
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D018836:Inflammation Mediators; D005337:Fibrin