Aptamer-modified FXa generation assays to investigate hypercoagulability in plasma from patients with ischemic heart disease
| Autor: | Giovanna Marchetti, Annalisa Castagna, Barry Woodhams, Marcello Baroni, Francesco Bernardi, Oliviero Olivieri, Nicola Martinelli, Barbara Lunghi, Mirko Pinotti, Filippo Stefanoni |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Aptamer Socio-culturale Coronary Artery Disease Factor VIIa Disease 030204 cardiovascular system & hematology Aptamers Thromboplastin Coronary artery disease 03 medical and health sciences Economica 0302 clinical medicine Thrombin Tissue factor pathway inhibitor Internal medicine medicine Humans Thrombophilia business.industry Long-term potentiation Hematology medicine.disease Factor VIIa-Antithrombin complex Endocrinology Quartile Diagnostic method Hypercoagulopathy 030220 oncology & carcinogenesis Factor Xa Ischemic heart business medicine.drug |
| Zdroj: | Thrombosis Research. 189:140-146 |
| ISSN: | 0049-3848 |
| DOI: | 10.1016/j.thromres.2020.03.007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect