Effect of acute exacerbations on circulating endothelial, clotting and fibrinolytic markers in COPD patients

Abstract

Patients with chronic obstructive pulmonary disease (COPD) are prone to clinical exacerbations that are associated with increased airway inflammation, a potent pro-thrombotic stimulus. Limited information is available on the mechanisms underlying the putative alterations of the endothelial-coagulative system during acute exacerbations. The aim was to investigate whether the activation of the endothelial-coagulative system occurs in association with the acute inflammatory response of COPD exacerbation. We monitored the blood levels of surrogate markers of inflammation: interleukin-6 (IL-6); endothelium damage: von Willebrand's factor (vWF); clotting activation: D-dimer (D-D), and prothrombin fragment 1+2 (F1+2); fibrinolytic response: plasminogen activator inhibitor 1 (PAI-1), in COPD subjects, during hospital admission and after clinical resolution. In 30 COPD subjects, IL-6, vWF, D-D and F1+2 levels were elevated during exacerbation and decreased significantly at clinical stability (IL-6, p = 0.005; vWF, p < 0.001; D-D, p < 0.001; F1+2, p < 0.001). PAI-1 levels did not change at exacerbation compared to clinically stable situations. Positive correlations were observed between several of the markers measured. Elevation of IL-6, vWF, D-D and F1+2 levels during COPD exacerbations implies a strict association between acute inflammation, endothelial activation and clotting initiation. This was not associated with a change in PAI-1, implying an increase in the fibrinolytic response to inflammation. The pro-thrombotic nature of COPD exacerbations sustained by enhanced clotting activation appears to be mitigated by excessive fibrinolysis.

Repeatability of and Relationship between Potential COPD Biomarkers in Bronchoalveolar Lavage, Bronchial Biopsies, Serum, and Induced Sputum

“…It showed a moderate reproducibility as shown in figure 1 I. Confounder analysis revealed that higher serum vWF levels in COPD patients could not be explained by changed covariates (FEV1 or pack-years, ANCOVA p-values for all confounders <0.01) and no significant association between smoking and vWF levels was found in the ARIC study [24]. Two reports that found vWF to be significantly increased in COPD patients with acute exacerbations [25] [26] support the potential clinical value of this blood marker.…”

Differences in the released endothelial microparticle subtypes between human pulmonary microvascular endothelial cells and aortic endothelial cells in vitro

“…In addi-tion, E-selectin EMPs were released from both aortic ECs and pulmonary microvascular ECs, although they were not released by H 2 O 2 and CSE stimulation. E-selectin has previously been reported to be upregulated when endothelial cells were activated, and endothelial activation was reported to be induced during COPD exacerbation [28,29]. We have previously shown that circulating E-selectin EMPs were released during exacerbation [3].…”

The Role of Mean Platelet Volume in Chronic Obstructive Pulmonary Disease Exacerbation

“…Elevated levels of von Willebrand factor, D-dimer, and prothrombin fragment 1ϩ2, being surrogate markers for inflammation, endothelial damage, and clotting activation, respectively, have been measured during an exacerbation of COPD. 19 A number of studies have demonstrated that subjects with COPD have an increased platelet count and also increased platelet ac- CRP ϭ C-reactive protein WBC ϭ white blood cell MPV ϭ mean platelet volume tivation in stable disease and further in the exacerbation period. 8,20 However, this platelet activation can follow different patterns as to mean platelet volume values in various diseases.…”