Anticoagulant therapy in acute lung injury.
OBJECTIVE
To review the rationale for evaluating anticoagulant therapies in acute lung injury (ALI) and to review selected data regarding the effectiveness of anticoagulants in animals and human patients with ALI and acute respiratory distress syndrome.


METHODS
Published literature on coagulation alterations and anticoagulant strategies in ALI during the past 25 yrs.


METHODS
In the lung, alveolar and interstitial fibrin deposition are the hallmarks of early phase ALI. Local procoagulant activity and reduced fibrinolysis constitute the rationale for anticoagulant use in the treatment of ALI. An activated complex of tissue factor and factor VIIa triggers procoagulant activity in the lung, with subsequent thrombin formation and fibrin deposition. Increased pulmonary vascular permeability and leukocyte accumulation have been successfully prevented in animals treated with tissue factor/activated factor VII pathway inhibitor. In humans, a phase II study evaluating tissue factor pathway inhibitor in the treatment of severe sepsis suggested that lung function in acute respiratory distress syndrome patients was improved. However, the phase III trial failed to demonstrate a survival benefit; data regarding respiratory dysfunction have not yet been published. Heparin, despite effectively inhibiting thrombin formation, has not shown consistent benefits in reducing lung injury, and its efficacy has not yet been evaluated in a controlled study. Antithrombin administration in animals has shown consistent benefits with ALI, but clinical studies have failed to demonstrate reductions in mortality and lung injury. Activated protein C administration has been shown to improve survival and lung function in both animal and clinical studies. Soluble thrombomodulin has been shown to improve ALI in animals, and it is currently being evaluated in humans with sepsis. Finally, plasminogen activators may improve gas exchange in ALI, but studies in humans are limited.
Laterre
Pierre-François
PF
Medical Surgical Intensive Care Unit, St. Luc University Hospital, Brussels, Belgium.
Wittebole
Xavier
X
Dhainaut
Jean-François
JF
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008074:Lipoproteins / Q000627:therapeutic use*; D010960:Plasminogen Activators / Q000627:therapeutic use*; D011486:Protein C / Q000627:therapeutic use; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D016896:Treatment Outcome
D000925:Anticoagulants; D008074:Lipoproteins; D011486:Protein C; C051928:lipoprotein-associated coagulation inhibitor; D006493:Heparin; D010960:Plasminogen Activators