PB0840 - Community-Treated Exacerbations of Chronic Obstructive Pulmonary Disease Are Associated With Upregulation in Prothrombotic Pathways and Persistent Impairments of Fibrinolysis.

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

MM

Mairi A. MacLeod

Clinical Research Fellow
Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
London, England, United Kingdom

Co-Author(s)

HS

Hassan Shahbakhti

Laboratory manager
Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
London, England, United Kingdom
RL

Ralph Lopez

Research nurse
Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
London, England, United Kingdom
AB

Aaron Braddy-Green

Clinical research fellow
Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
London, England, United Kingdom
SB

Sam Bartlett-Pestell

Clinical research fellow
Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
London, England, United Kingdom
SV

Saravanan Vinayagam

researcher
Department of Haematology, Imperial College Healthcare NHS Trust, London, UK
London, England, United Kingdom
NK

Nilanthi Karawitage

researcher
Department of Haematology, Imperial College Healthcare NHS Trust, London, UK
London, England, United Kingdom

Presenting Author(s)

JM

James Manning

Academic foundation doctor
Department of Immunology and Inflammation, Centre for Haematology, Imperial College London, London, UK
London, England, United Kingdom

Co-Author(s)

Mike Laffan

Professor of haemostasis & thrombosis
Imperial College London, London. UK
London, England, United Kingdom
JW

Jadwiga A. Wedzicha

Professor of respiratory medicine
Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
London, England, United Kingdom
DA

Deepa J. Arachchillage, MD

Consultant haematologist, honorary senior lecturer & MRC CARP fellow
Department of immunity & inflammation, Centre for Haematology, Imperial College London, London. UK
London, England, United Kingdom

Background: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with an increased risk of cardiovascular events, persisting beyond the acute period of illness. Inflammation associated with acute exacerbation of COPD may lead to upregulation of prothrombic and downregulation of fibrinolytic pathways, likely contributing to vascular events. The impact of less severe exacerbations (community-treated) on prothrombotic and fibrinolytic pathways and the speed of resolution of these abnormalities is unknown.

Aims: To assess changes in prothrombotic and fibrinolytic pathways during community-treated COPD exacerbation, and its recovery.

Methods: Blood samples were collected from patients with COPD at baseline (stable respiratory symptoms), acute exacerbation (community-treated) and in a proportion of patients during exacerbation recovery (2- and 6- weeks post-exacerbation). At each stage, prothrombotic phenotype and fibrinolytic potential were assessed using thrombin generation (TG) by calibrated automated thrombography and turbidimetric assay respectively in addition to fibrinogen and D-dimer levels.

Results: In total, 65 exacerbations from 42 patients (mean age 74±7.9 years and 54.8% male) were assessed. 33 exacerbations had recovery data. There were significant increases in peak-thrombin (236.5 vs. 242.4nM, p=0.0003); endogenous thrombin potential (ETP) (1147.5 vs. 1226nM/min, P=0.0004) and fibrinogen levels (3.7 vs 3.9g/L, p=0.02). Fibrinolysis was significantly reduced as measured by 50% clot lysis time (CLT) (67 vs. 80.5mins, p=0.007) at exacerbation compared to baseline. There was no difference in D-dimer levels (361 vs. 453.5 (ng/mL) FEU, p=0.27) (Table 1). This persisted in sensitivity analysis (Table 1). Although TG parameters returned to baseline two weeks post-exacerbation, fibrinolysis remained impaired at 2 weeks post-exacerbation (baseline vs. 2-week CLT, 62.3 vs. 87.3mins, p=0.004) and had not returned to baseline by 6 weeks (62.3 vs. 72.3mins, p=0.28) (Figure 1).

Conclusion(s): Community-treated COPD exacerbations are associated with increased TG and persistent impairment of fibrinolysis. The impact of these on well-known thromboembolic complications of COPD exacerbation should be further evaluated.