title: 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.
authors.affiliation: Dipartimento di Medicina Interna e Specialistica, Università di Catania, Catania, Italy, polosa@unict.it.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Polosa
authors.forename: Mario
authors.initials: M
authors.lastname: Malerba
authors.forename: Rossella R
authors.initials: RR
authors.lastname: Cacciola
authors.forename: Jaymin B
authors.initials: JB
authors.lastname: Morjaria
authors.forename: Cinzia
authors.initials: C
authors.lastname: Maugeri
authors.forename: Gaetano
authors.initials: G
authors.lastname: Prosperini
authors.forename: Raimondo
authors.initials: R
authors.lastname: Gullo
authors.forename: Lucia
authors.initials: L
authors.lastname: Spicuzza
authors.forename: Alessandro
authors.initials: A
authors.lastname: Radaeli
authors.forename: Giuseppe U
authors.initials: GU
authors.lastname: Di Maria
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001777:Blood Coagulation / Q000502:physiology*; D001784:Blood Gas Analysis; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011516:Prothrombin; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D013147:Spirometry; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D014841:von Willebrand Factor; D011516:Prothrombin