Evaluation of Prothrombotic Biomarkers in Stable and Exacerbation Phases of Chronic Obstructive Pulmonary Disease: A Case-Control Study.

Introduction  Chronic Obstructive Pulmonary Disease (COPD) is increasingly recognized not only as a pulmonary condition but as a systemic disorder with significant cardiovascular implications. Acute exacerbations of COPD (AECOPD) further elevate this risk, potentially through a heightened prothrombotic state. This study aimed to evaluate and compare the levels of select prothrombotic biomarkers - fibrinogen, C-reactive protein (CRP), D-dimer, von Willebrand Factor (vWF), homocysteine, lactate dehydrogenase (LDH), and platelet-to-lymphocyte ratio (PLR) - in patients with stable COPD and AECOPD, and to assess their diagnostic and prognostic significance. Materials and methods This case-control study was conducted over a year at King George's Medical University, Lucknow, India and compared prothrombotic biomarkers in patients with AECOPD and stable COPD. Eligible participants were aged between 30 and 80 years old and diagnosed with COPD, as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. CRP, fibrinogen, D-dimer, and vWF were analyzed using enzyme-linked immunosorbent assays (ELISA). Statistical analysis involved t-tests, Chi-square, and correlation methods. A p-value <0.05 was considered significant. Ethical approval and informed consent were obtained from all participants. Results
  Among the 30 stable COPD and 30 AECOPD patients involved in this study, significant elevations in serum fibrinogen, D-dimer, and vWF levels were observed in the exacerbation group. Mean fibrinogen levels were markedly higher in the AECOPD patients (mean±SD: 577.23±112.12 mg/dL) compared to stable COPD (391.2±87.15 mg/dL; p<0.0001), and similar trends were seen for D-dimer (0.93±0.28 vs. 0.46±0.19 µg/mL) and vWF (159.2±36.42 vs. 116.6±30.23 IU/dL). Receiver operating characteristic (ROC) using the area under curve (AUC) analysis identified fibrinogen as the most robust discriminator for AECOPD (AUC=0.89), D-dimer (AUC=0.82), and vWF (AUC=0.74). Other biomarkers like homocysteine, LDH, and PLR also exhibited significant elevations during exacerbations, correlating moderately with spirometric severity and symptom burden. Conclusions
  The findings suggest that AECOPD is associated with a pronounced prothrombotic milieu. Biomarkers such as fibrinogen, vWF, and D-dimer hold strong potential as indicators for early detection and risk stratification of acute exacerbations. Integrating these markers into routine COPD monitoring protocols may enhance clinical decision making, particularly in predicting exacerbation risk and guiding anti-inflammatory or anticoagulant therapies. Further longitudinal studies are warranted to validate their role in forecasting adverse events and long-term outcomes.