Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome.

Pubmed ID: 17667242

Pubmed Central ID: PMC2764536

Journal: Critical care medicine

Publication Date: Aug. 1, 2007

Affiliation: Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. lorraine.ware@vanderbilt.edu

MeSH Terms: Humans, Male, Female, United States, Logistic Models, Middle Aged, Multivariate Analysis, Prognosis, Hospital Mortality, Predictive Value of Tests, Risk, Blood Coagulation Disorders, Fibrinolysis, Plasminogen Activator Inhibitor 1, Protein C, Biomarkers, Respiratory Distress Syndrome

Grants: R37 HL051856, R37 HL051856-14, HL 04201, HL 51856, HL 70521, HL081332, N0-1 HR 46054, N0-1 HR 46055, N0-1 HR 46056, N0-1 HR 46057, N0-1 HR 46058, N0-1 HR 46059, N0-1 HR 46060, N0-1 HR 46061, N0-1 HR 46062, N0-1 HR 46063, N0-1 HR 46064, P50 HL74005, U01 HL081332, N01HR46054, R01 HL051856, P50 HL074005, K23 HL004201, K08 HL070521

Authors: Thompson BT, Parsons PE, Matthay MA, Ware LB, Eisner MD, Januzzi JL

Cite As: Ware LB, Matthay MA, Parsons PE, Thompson BT, Januzzi JL, Eisner MD, National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome. Crit Care Med 2007 Aug;35(8):1821-8.

Studies:

Acute Respiratory Distress Network (ARDSNet) Studies 01 and 03 Lower versus higher tidal volume, ketoconazole treatment and lisofylline treatment (ARMA/KARMA/LARMA)

Abstract

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. DESIGN: 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. SETTING: Ten university medical centers. PATIENTS: 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. MEASUREMENTS AND MAIN 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.