Activation of Coagulation and Fibrinolysis in Acute Respiratory Distress Syndrome: A Prospective Pilot Study

Agnese Ozolina; Marina Sarkele; Olegs Sabelnikovs; Andrejs Skesters; Inta Jaunalksne; Jelena Serova; Talis Ievins; Lars J Bjertnaes; Indulis Vanags

doi:10.3389/fmed.2016.00064

Activation of Coagulation and Fibrinolysis in Acute Respiratory Distress Syndrome: A Prospective Pilot Study

Front Med (Lausanne). 2016 Nov 28:3:64. doi: 10.3389/fmed.2016.00064. eCollection 2016.

Authors

Agnese Ozolina¹, Marina Sarkele², Olegs Sabelnikovs², Andrejs Skesters³, Inta Jaunalksne⁴, Jelena Serova⁴, Talis Ievins⁵, Lars J Bjertnaes⁶, Indulis Vanags²

Affiliations

¹ Department of Cardiac Surgery, Pauls Stradins Clinical University Hospital, Riga, Latvia; Riga Stradins University, Riga, Latvia.
² Riga Stradins University, Riga, Latvia; Department of Anesthesiology and Intensive Care Unit, Pauls Stradins Clinical University Hospital, Riga, Latvia.
³ Laboratory of Biochemistry, Riga Stradins University , Riga , Latvia.
⁴ Clinical Immunology Centre, Pauls Stradins Clinical University Hospital , Riga , Latvia.
⁵ Department of Cardiac Surgery, Pauls Stradins Clinical University Hospital , Riga , Latvia.
⁶ Anesthesia and Critical Care Research Group, Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø , Tromsø , Norway.

Abstract

Introduction: 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.

Materials and 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 at T₇ in 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.

Conclusion: 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.

Keywords: acute respiratory distress syndrome; lung injury; plasminogen activator inhibitor-1; tissue factor; tissue plasminogen activator; ventilator-associated lung injury.