Effect of recombinant factor VIIa on melagatran-induced inhibition of thrombin generation and platelet activation in healthy volunteers
| Autor: | Troy C. Sarich, Stig L. Boström, Karin Wåhlander, Michael Wolzt, Ulf G. Eriksson, Margareta Elg, Jeffrey I. Weitz, Marcel Levi, Mia Svensson, Maria Eriksson-Lepkowska |
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| Přispěvatelé: | Amsterdam Cardiovascular Sciences, Amsterdam institute for Infection and Immunity, General Internal Medicine |
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Benzylamines Time Factors Ximelagatran Glycine Factor VIIa Pharmacology Thrombin medicine Humans Drug Interactions Single-Blind Method Platelet Platelet activation Prothrombin time Dose-Response Relationship Drug biology medicine.diagnostic_test business.industry Thrombosis Hematology Factor VII Platelet Activation Recombinant Proteins Recombinant factor VIIa Direct thrombin inhibitor Anesthesia biology.protein Azetidines Blood Coagulation Tests business Biomarkers circulatory and respiratory physiology medicine.drug Partial thromboplastin time |
| Zdroj: | Thrombosis and haemostasis, 91(6), 1090-1096. Schattauer GmbH |
| ISSN: | 2567-689X 0340-6245 |
| DOI: | 10.1160/th03-09-0605 |
| Popis: | SummaryThe objectives were to investigate whether activation of the extrinsic coagulation cascade by recombinant factor VIIa (rFVIIa) reverses the inhibition of thrombin generation and platelet activation by melagatran, the active form of the oral direct thrombin inhibitor ximelagatran. In a single-blind, randomized, parallel-group study, volunteers (20 per group) received a 5-hour intravenous (iv) infusion to achieve steadystate melagatran plasma concentrations of approximately 0.5 µmol/L, with a single iv bolus of rFVIIa (90 µg/kg) or placebo at 60 minutes. Prothrombin fragment 1+2, thrombin-antithrombin complex, fibrinopeptide A, β-thromboglobulin, and thrombin-activatable fibrinolysis inhibitor were quantified for venous and shed blood. Activated partial thromboplastin time (APTT), prothrombin time (PT), endogenous thrombin potential, thrombus precursor protein (TpP), and plasmin-α2-antiplasmin complex concentrations were determined in venous blood. Shed blood volume was measured. Melagatran reduced markers of thrombin generation and platelet activation in shed blood and prolonged APTT. rFVIIa increased FVIIa activity, PT, and TpP in venous blood. All other parameters were unaffected. In conclusion, rFVIIa did not reverse the anticoagulant effects of high constant concentrations of melagatran. However, the potential value of higher, continuous or repeated doses of rFVIIa or its use with lower melagatran concentrations has not been excluded. |
| Databáze: | OpenAIRE |
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