title: Activation of Coagulation and Fibrinolysis in Acute Respiratory Distress Syndrome: A Prospective Pilot Study.
abstract: BACKGROUND
  Coagulation and fibrinolysis remain sparsely addressed with regards to acute respiratory distress syndrome (ARDS). We hypothesized that ARDS development might be associated with changes in plasma coagulation and fibrinolysis. Our aim was to investigate the relationships between ARDS diagnosis and plasma concentrations of tissue factor (TF), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) in mechanically ventilated patients at increased risk of developing ARDS.
  
  
  METHODS
  We performed an ethically approved prospective observational pilot study. Inclusion criteria were patients with PaO2/FiO2< 300 mmHg admitted to the intensive care unit (ICU) for mechanical ventilation for 24 h, or more, because of one or more disease conditions associated with increased risk of developing ARDS. Exclusion criteria were age below 18 years; cardiac disease. We sampled plasma prospectively and compared patients who developed ARDS with those who did not using descriptive statistics and chi-square analysis of baseline demographical and clinical data. We also analyzed plasma concentrations of TF, t-PA, and PAI-1 at inclusion (T0) and on third (T3) and seventh day (T7) of the ICU stay with non-parametric statistics inclusive their sensitivity and specificity associated with the development of ARDS using receiver operating characteristic curve analysis. Statistical significance:p< 0.05.
  
  
  RESULTS
  Of 24 patients at risk, 6 developed mild ARDS and 4 of each moderate or severe ARDS, respectively, 3 ± 2 (mean ± SD) days after inclusion. Median plasma concentrations of TF and PAI-1 were significantly higher atT7in patients with ARDS, as compared to non-ARDS. Simultaneously, we found moderate correlations between plasma concentrations of TF and PAI-1, TF and PaO2/FiO2, and positive end-expiratory pressure and TF. TF plasma concentration was associated with ARDS with 71% sensitivity and 100% specificity, a cut off level of 145 pg/ml and AUC 0.78,p= 0.02. PAI-1 displayed 64% sensitivity and 100% specificity with a cut off concentration of 117.5 pg/ml and AUC 0.77,p= 0.02. t-PA did not change significantly during the observation time.
  
  
  CONCLUSIONS
  This pilot study showed that increased plasma concentrations of TF and PAI-1 might support ARDS diagnoses in mechanically ventilated patients after 7 days in ICU.
authors.affiliation: Department of Cardiac Surgery, Pauls Stradins Clinical University Hospital, Riga, Latvia; Riga Stradins University, Riga, Latvia.
authors.forename: Agnese
authors.initials: A
authors.lastname: Ozolina
authors.affiliation: Riga Stradins University, Riga, Latvia; Department of Anesthesiology and Intensive Care Unit, Pauls Stradins Clinical University Hospital, Riga, Latvia.
authors.forename: Marina
authors.initials: M
authors.lastname: Sarkele
authors.affiliation: Riga Stradins University, Riga, Latvia; Department of Anesthesiology and Intensive Care Unit, Pauls Stradins Clinical University Hospital, Riga, Latvia.
authors.forename: Olegs
authors.initials: O
authors.lastname: Sabelnikovs
authors.affiliation: Laboratory of Biochemistry, Riga Stradins University , Riga , Latvia.
authors.forename: Andrejs
authors.initials: A
authors.lastname: Skesters
authors.affiliation: Clinical Immunology Centre, Pauls Stradins Clinical University Hospital , Riga , Latvia.
authors.forename: Inta
authors.initials: I
authors.lastname: Jaunalksne
authors.affiliation: Clinical Immunology Centre, Pauls Stradins Clinical University Hospital , Riga , Latvia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Serova
authors.affiliation: Department of Cardiac Surgery, Pauls Stradins Clinical University Hospital , Riga , Latvia.
authors.forename: Talis
authors.initials: T
authors.lastname: Ievins
authors.affiliation: Anesthesia and Critical Care Research Group, Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø , Tromsø , Norway.
authors.forename: Lars J
authors.initials: LJ
authors.lastname: Bjertnaes
authors.affiliation: Riga Stradins University, Riga, Latvia; Department of Anesthesiology and Intensive Care Unit, Pauls Stradins Clinical University Hospital, Riga, Latvia.
authors.forename: Indulis
authors.initials: I
authors.lastname: Vanags
keywords: acute respiratory distress syndrome; lung injury; plasminogen activator inhibitor-1; tissue factor; tissue plasminogen activator; ventilator-associated lung injury