Coagulation and fibrinolysis in human acute lung injury--new therapeutic targets?
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common, life-threatening causes of acute respiratory failure that arise from a variety of local and systemic insults. The need for new specific therapies has led a number of investigators to examine the role of altered coagulation and fibrinolysis in the pathogenesis of ALI/ARDS. This review summarizes our current understanding of coagulation and fibrinolysis in human ALI/ARDS with an emphasis on pathways that could be potential therapeutic targets including the tissue factor pathway, the protein C pathway and modulation of fibrinolysis via plasminogen activator inhibitor-1. The available data suggest that clinical ALI and ARDS are characterized by profound alterations in both systemic and intra-alveolar coagulation and fibrinolysis. Fibrin deposition in the airspaces and lung microvasculature likely results from both activation of the coagulation cascade and impaired fibrinolysis, triggered by inflammation. Modulation of fibrin deposition in the lung through targeting activation and modulation of coagulation as well as fibrinolysis may be an important therapeutic target in clinical ALI/ARDS that deserves further exploration.
Ware
Lorraine B
LB
Division of Allergy, Pulmonary, and Critical Care, Department of Medicine Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA. lorraine.ware@vanderbilt.edu
Bastarache
Julie A
JA
Wang
Ling
L
D001777:Blood Coagulation; D005342:Fibrinolysis; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D011486:Protein C / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000628:therapy*; D018180:Thrombomodulin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism
D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D018180:Thrombomodulin; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D010960:Plasminogen Activators