Activation of prothrombotic pathways during community-treated exacerbation of COPD

<bold>Introduction:</bold> Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with an increased risk of arterial and venous thrombosis. Derangements in prothrombotic and fibrinolytic pathways at severe hospitalised exacerbations have been described. We aimed to explore if similar alterations occur during community-treated events. <bold>Methods:</bold> Blood samples were collected from patients with COPD at baseline, exacerbation and, in a subgroup, recovery. D-dimer, fibrinogen, complement activation (C3a, C5a, SC5b9 and BB fragment), functional assessment of thrombin generation (calibrated automated thrombography) and fibrinolysis (turbidimetry) were undertaken. Paired Wilcoxon tests were used to assess change in each biomarker at exacerbation. Sensitivity analysis corrected for multiple exacerbations per patient. <bold>Results:</bold> 64 exacerbations from 43 patients (mean age 73.8±8), 57.1% male) were included. Exacerbations were associated with increased thrombin generation (peak-thrombin concentration 242.4 vs. 236.7nM, p=0.0003; endogenous thrombin potential 1226 vs. 1135.6nM/min, p=0.0004) and impaired fibrinolysis (clot lysis time (CLT) 80.5 vs. 67mins, p=0.007) when compared to baseline. Fibrinogen (3.9 vs. 3.7g/L, p=0.02), C3a (140.8 vs. 82.1ng/mL, p=0.004), C5a (7.3 vs.6.9ng/mL, p=0.0002) and SC5b9 (210.7 vs. 172.8ng/mL, p=0.0004) were also increased. CLT remained elevated at 2 weeks (p=0.004), normalising by 6 weeks. All relationships persisted in sensitivity analysis. <bold>Conclusion:</bold> Community-treated COPD exacerbations are associated with activation of procoagulant pathways and prolonged impairments of fibrinolysis. Future studies should address the impact of this on thrombotic risk at exacerbation.