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

Abstract

IntroductionCoagulation 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 methodsWe 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.ResultsOf 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.ConclusionThis 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.

Effects of nebulized antithrombin and heparin on inflammatory and coagulation alterations in an acute lung injury model in rats

“…Nonetheless, an excessive inhibition of procoagulant factors might also be deleterious, as was observed by Basterache et al, who suggested that the complete deficiency of TF in an ALI model lead to an increase of intra‐alveolar hemorrhage. In contrast, other studies indicate that high levels of TF result in higher depositions of fibrin, which is associated with a worst outcome . In our results, nebulized anticoagulants reduced TF levels but not completely, attenuating lung coagulopathy and fibrin deposition in the lungs without producing intra‐alveolar hemorrhage.…”

“…In contrast, other studies indicate that high levels of TF result in higher depositions of fibrin, which is associated with a worst outcome. 40,41 In our results, nebulized anticoagulants reduced TF levels but not completely, attenuating lung coagulopathy and fibrin deposition in the lungs without producing intra-alveolar hemorrhage.…”

ITRAQ-Based Proteomics Analysis of Acute Lung Injury Induced by Oleic Acid in Mice

“…Some experimental evidence has revealed that abnormalities in the pro-coagulation and fibrinolysis protein pathways are features of ALI [23,24]. ALI is accompanied by fibrin deposition in the lung and increased plasminogen activator inhibitor expression in bronchoalveolar lavage (BAL) fluid.…”

The versatile heparin in COVID‐19

“…Activation of the coagulation system has been shown to be relevant in the pathogenesis of ARDS. Ozoline et al demonstrated that median plasma concentrations of tissue factor and plasminogen activator inhibitor‐1 were significantly higher at day seven in patients with ARDS, as compared to non‐ARDS 12 . The mechanisms contributing to this lung coagulopathy are localized tissue factor‐mediated thrombin generation, and depression of bronchoalveolar plasminogen activator‐mediated fibrinolysis, mediated by the PAI‐1 increase.…”

“…The mechanisms contributing to this lung coagulopathy are localized tissue factor‐mediated thrombin generation, and depression of bronchoalveolar plasminogen activator‐mediated fibrinolysis, mediated by the PAI‐1 increase. 12,13 Treatment with heparin may thus be helpful in mitigating this pulmonary coagulopathy. A meta‐analysis noted that adjunctive treatment with LMWH within the initial 7‐day onset of ARDS reduces the risk of 7‐day mortality by 48% and the risk of 28‐day mortality by 37% in addition to significantly improving PaO2/FiO2 ratio (the improvement is particularly important in the subgroup receiving high‐dose LMWH of ≥ 5000 units/d) 14 .…”