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Aptamer-modified FXa generation assays to investigate hypercoagulability in plasma from patients with ischemic heart disease.
Baroni, Marcello; Martinelli, Nicola; Lunghi, Barbara; Marchetti, Giovanna; Castagna, Annalisa; Stefanoni, Filippo; Pinotti, Mirko; Woodhams, Barry; Olivieri, Oliviero; Bernardi, Francesco.
Affiliation
  • Baroni M; University of Ferrara, Department of Life Sciences and Biotechnology, 44121 Ferrara, Italy. Electronic address: brnmcl@unife.it.
  • Martinelli N; University of Verona, Department of Medicine, Unit of Internal Medicine, Policlinico G.B. Rossi, 37134 Verona, Italy.
  • Lunghi B; University of Ferrara, Department of Life Sciences and Biotechnology, 44121 Ferrara, Italy.
  • Marchetti G; University of Ferrara, Department of Biomedical and Specialty Surgical Sciences, 44121 Ferrara, Italy.
  • Castagna A; University of Verona, Department of Medicine, Unit of Internal Medicine, Policlinico G.B. Rossi, 37134 Verona, Italy.
  • Stefanoni F; University of Verona, Department of Medicine, Unit of Internal Medicine, Policlinico G.B. Rossi, 37134 Verona, Italy.
  • Pinotti M; University of Ferrara, Department of Life Sciences and Biotechnology, 44121 Ferrara, Italy.
  • Woodhams B; Haemacon Ltd, Bromley, Kent, UK.
  • Olivieri O; University of Verona, Department of Medicine, Unit of Internal Medicine, Policlinico G.B. Rossi, 37134 Verona, Italy.
  • Bernardi F; University of Ferrara, Department of Life Sciences and Biotechnology, 44121 Ferrara, Italy.
Thromb Res ; 189: 140-146, 2020 05.
Article in En | MEDLINE | ID: mdl-32224381
BACKGROUND: High plasma levels of activated Factor VII-Antithrombin complex (FVIIa-AT) have been associated with an increased risk of cardiovascular mortality in patients with stable coronary artery disease (CAD). OBJECTIVES: To investigate if FVIIa-AT levels are associated with activated factor X generation (FXaG) in modified assays. PATIENTS/METHODS: Forty CAD patients were characterized for FVIIa-AT levels by ELISA and for FXaG in plasma. Novel fluorogenic FXaG assays, based on aptamers inhibiting thrombin and/or tissue factor pathway inhibitor (TFPI), were set up. RESULTS: FXaG correlated with FVIIa-AT levels (RAUC = 0.393, P = 0.012). The combination of thrombin inhibition and FXaG potentiation by using anti-thrombin and anti-TFPI aptamers, respectively, favors the study of time parameters. The progressive decrease in lag time from the lowest to the highest FVIIa-AT quartile was magnified by combining TFPI and thrombin inhibitory aptamers, thus supporting increased FXaG activity in the coagulation initiation phase. By exploring FXaG rates across FVIIa-AT quartiles, the largest relative differences were detectable at the early times (the highest versus the lowest quartile; 5.0-fold, P = 0.005 at 45 s; 3.5-fold, P = 0.001 at 55 s), and progressively decreased over time (2.3-fold, P = 0.002 at 75 s; 1.8-fold, P = 0.008 at 95 s; 1.6-fold, P = 0.022 at 115 s). Association between high FVIIa-AT levels and increased FXaG was independent of F7 -323 A1/A2 polymorphism influencing FVIIa-AT levels. CONCLUSIONS: High FVIIa-AT plasma levels were associated with increased FXaG. Hypercoagulability features were specifically detectable in the coagulation initiation phase, which may have implications for cardiovascular risk prediction by either FVIIa-AT complex measurement or modified FXaG assays.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Coronary Artery Disease / Thrombophilia Type of study: Prognostic_studies Limits: Humans Language: En Journal: Thromb Res Year: 2020 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Coronary Artery Disease / Thrombophilia Type of study: Prognostic_studies Limits: Humans Language: En Journal: Thromb Res Year: 2020 Document type: Article Country of publication: United States