Elevated levels of plasminogen activator inhibitor-1 in pulmonary edema fluid are associated with mortality in acute lung injury.
The alveolar fibrinolytic system is altered in acute lung injury (ALI). Levels of the fibrinolytic protease inhibitor, plasminogen activator inhibitor-1 (PAI-1), are too low in bronchoalveolar lavage to address its prognostic significance. This study was performed to assess whether PAI-1 antigen in undiluted pulmonary edema fluid levels can identify patients with ALI and predict their outcome. PAI-1 antigen levels in both plasma and edema fluid were higher in ALI compared with hydrostatic edema, and edema fluid PAI-1 values identified those with ALI with high sensitivity and specificity. Both the high plasma and edema fluid PAI-1 antigen values were associated with a higher mortality rate and fewer days of unassisted ventilation in patients with ALI. Differences in PAI-1 activity were concordant with levels of PAI-1 antigen. Although the fibrin-derived alveolar D-dimer levels were strikingly similar in both groups, ALI patients had a higher relative proportion of D-monomer. In conclusion, PAI-1 levels in edema fluid and plasma identify those with ALI that have a poor prognosis. The data indicate that fibrin turnover in early ALI is a consequence of a rapid fibrinogen influx and fractional fibrinolytic inhibition.
Department of Pediatrics, University of Alabama, Birmingham, Alabama 35294, USA.
Priya
P
Prabhakaran
Lorraine B
LB
Ware
Kimberly E
KE
White
Michael T
MT
Cross
Michael A
MA
Matthay
Mitchell A
MA
Olman
D000208:Acute Disease; D000328:Adult; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay; D015633:Extravascular Lung Water / Q000378:metabolism*; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D006874:Hydrostatic Pressure; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011654:Pulmonary Edema / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D018805:Sepsis / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality
D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; D005337:Fibrin; D005340:Fibrinogen