title: Fibrinolytic status in acute coronary syndromes: evidence of differences in relation to clinical features and pathophysiological pathways.
abstract: Limited data are available on the role of innate fibrinolysis in acute coronary syndromes (ACS). In the present study we evaluated the dynamic alterations of fibrinolytic markers in patients presenting with ACS. Tissue-type-(tPA) and urokinase type-(uPA) plasminogen activators, plasminogen activator inhibitor (PAI-1) antigen and activity and thrombin activatable fibrinolysis inhibitor (TAFI) were analysed in 50 patients with ST elevation myocardial infarction (STEMI), 47 non-STEMI patients (NSTEMI), 40 patients with stable coronary artery disease (CAD) and 39 controls. The parameters were measured on day 1 and days 3, 7 and 30. Counts of monocyte subsets, monocyte-platelet aggregates and plasma inflammatory cytokines were assessed on admission. On day 1, TAFI was higher in NSTEMI vs. STEMI (p<0.001) while PAI-1 activity was higher in STEMI (p<0.001). In STEMI, uPA activity levels was low on day 1 but significantly increased on day 30 (p<0.001). TAFI levels were increased in NSTEMI on day 1 and gradually reduced by day 30 (p<0.05). In STEMI, TAFI levels peaked at day 7 (p<0.05) and dropped significantly by day 30 (p<0.05). CD14++CD16+ monocytes were independently associated with PAI-1 activity in ACS (p=0.03). Monocyte-platelet aggregates rather than platelet-free monocytes were an independent determinant of tPA, PAI-1 antigen and TAFI on a multivariate analysis (p<0.05). There are significant differences in fibrinolytic activity between patients with STEMI and NSTEMI. These changes could reflect the role of these factors in post-MI myocardial healing. Monocyte-platelet interactions are independently associated with the regulation of the fibrinolytic status in ACS.
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK.
authors.forename: Eduard
authors.initials: E
authors.lastname: Shantsila
authors.forename: Silvia
authors.initials: S
authors.lastname: Montoro-García
authors.forename: Luke D
authors.initials: LD
authors.lastname: Tapp
authors.forename: Stavros
authors.initials: S
authors.lastname: Apostolakis
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Wrigley
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000503:physiopathology*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000502:physiology*; D025901:Carboxypeptidase B2 / Q000097:blood; D002448:Cell Adhesion; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D009203:Myocardial Infarction / Q000175:diagnosis / Q000503:physiopathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017452:Receptors, IgG / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D017395:Plasminogen Activator Inhibitor 1; D017452:Receptors, IgG; D025901:Carboxypeptidase B2; D012697:Serine Endopeptidases; C047211:urokinase-converting protease; D010959:Tissue Plasminogen Activator