Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome.
OBJECTIVE
The coagulation and inflammatory cascades may be linked in the pathogenesis of acute lung injury and acute respiratory distress syndrome. However, direct evidence for the contribution of abnormalities in coagulation and fibrinolysis proteins to outcomes in patients with acute lung injury/acute respiratory distress syndrome is lacking.


METHODS
Retrospective measurement of plasma levels of protein C and plasminogen activator inhibitor-1 in plasma samples that were collected prospectively as part of a large multicenter clinical trial. The primary outcome was hospital mortality. To evaluate the potential additive value of abnormalities of these biomarkers, the excess relative risk of death was calculated for each combination of quartiles of protein-C and plasminogen activator inhibitor-1 levels.


METHODS
Ten university medical centers.


METHODS
The study included 779 patients from a multicenter clinical trial of a protective ventilatory strategy in acute lung injury/acute respiratory distress syndrome and 99 patients with acute cardiogenic pulmonary edema, as well as ten normal controls.


RESULTS
Compared with plasma from controls and patients with acute cardiogenic pulmonary edema, baseline protein-C levels were low and baseline plasminogen activator inhibitor-1 levels were elevated in acute lung injury/acute respiratory distress syndrome. By multivariate analysis, lower protein C and higher plasminogen activator inhibitor-1 were strong independent predictors of mortality, and ventilator-free and organ-failure-free days. Plasminogen activator inhibitor-1 and protein C had a synergistic interaction for the risk of death.


CONCLUSIONS
Early acute lung injury/acute respiratory distress syndrome is characterized by decreased plasma levels of protein C and increased plasma levels of plasminogen activator inhibitor-1 that are independent risk factors for mortality and adverse clinical outcomes. Measurement of plasminogen activator inhibitor-1 and protein-C levels may be useful to identify those at highest risk of adverse clinical outcomes for the development of new therapies.
Ware
Lorraine B
LB
Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. lorraine.ware@vanderbilt.edu
Matthay
Michael A
MA
Parsons
Polly E
PE
Thompson
B Taylor
BT
Januzzi
James L
JL
Eisner
Mark D
MD
D015415:Biomarkers / Q000097:blood; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D005342:Fibrinolysis; D017052:Hospital Mortality; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011486:Protein C / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D012306:Risk; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C