Dokument: Effekte von direkten Faktor-Xa-Inhibitoren auf die Thrombozytenfunktion von Patienten mit Vorhofflimmern
| Titel: | Effekte von direkten Faktor-Xa-Inhibitoren auf die Thrombozytenfunktion von Patienten mit Vorhofflimmern | |||||||
| Weiterer Titel: | Effects of direct factor-Xa-inhibitors on platelet function of patients with atrial fibrillation | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=53561 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20200701-104533-6 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | M'Pembele, René [Autor] | |||||||
| Dateien: |
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| Beitragende: | PD Dr. med. Polzin, Amin [Gutachter] Schneppendahl, Johannes [Gutachter] | |||||||
| Stichwörter: | Rivaroxaban, Thrombozyten, Aggregation, Vorhofflimmern | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Seit einigen Jahren werden direkte Faktor-Xa-Inhibitoren wie Rivaroxaban als Antikoagulanzien bei Vorhofflimmern empfohlen. Aktuelle Studien zeigen neben der Reduktion von Schlaganfällen zudem eine Mortalitätssenkung durch Rivaroxaban. Thrombozyten spielen eine große Rolle in der Entstehung ischämischer Ereignisse. Daher hypothetisierten wir in dieser Arbeit, dass direkte Faktor-Xa-Inhibitoren Einfluss auf die Thrombozytenaktivierung haben. Dazu wurden Versuche an 62 Patienten durchgeführt. Es wurden die Thrombozytenfunktion in der Lichttransmissionsaggregometrie und der Mehrfachelektrodenaggregometrie, das endogene Thrombinpotenzial (ETP) und die Thrombozytenadhäsion in einer Flusskammer unter Einnahme von Rivaroxaban sowie Apixaban gemessen. Die Freisetzung von Thromboxan aus Thrombozyten wurde nach Stimulation mit Faktor Xa (FXa) erhoben. Nach Einnahme von Rivaroxaban oder Apixaban waren die Thrombozytenaggregation, die Thrombozytenadhäsion und das ETP im Vergleich zum Ausgangswert erniedrigt. FXa konnte als potenter, direkter, dosisabhängiger Aktivator der Thrombozytenaggregation und Thromboxanbildung dargestellt werden. Dieser Effekt war unabhängig von anderen plasmatischen Gerinnungsfaktoren wie Thrombin. Die Aktivierung ließ sich dosisabhängig durch Rivaroxaban und Vorapaxar, einem PAR-1 Thrombinrezeptorantagonist, in gleichem Maße hemmen. Zusammenfassend konnte gezeigt werden, dass FXa eine wichtige Rolle in der Aktivierung von Thrombozyten spielt. Diese Aktivierung bindet direkte Effekte von FXa auf PAR-1 Rezeptoren mit ein. Der Mechanismus kann durch Faktor-Xa-Inhibitoren gehemmt werden, was in einer geringeren Thrombozytenreaktivität resultiert. Patienten mit Vorhofflimmern und einem hohen Risiko für ein ischämisches Ereignis könnten daher von diesem Effekt profitieren.Direct factor Xa inhibitors like Rivaroxaban are recommended to prevent stroke in patients with atrial fibrillation. Recent studies showed that therapy with Rivaroxaban not only decreases the risk of thromboembolic events, but also mortality. This might be due to other effects than the inhibition of plasmatic coagulation factors. As platelets play a major role in pathophysiology of cardiovascular events, this thesis focused on the effects of direct factor Xa inhibitors on platelet reactivity. Therefore 62 patients were enrolled in a trial. Platelet function was measured by light transmission aggregometry (LTA), multiple electrode aggregometry and endogenous thrombin potential (ETP) before and after intake of direct factor Xa inhibitors. In addition, Platelet adhesion was assessed in a flow chamber and the release of thromboxane from platelets was measured after stimulation with factor Xa (FXa). Platelet aggregation, platelet adhesion and ETP were reduced, compared to baseline, after medication with Rivaroxaban or Apixaban. We identified FXa as a potent, dose dependant activator of platelet aggregation in LTA. This effect was independent from thrombin. This activation could be inhibited dose dependently by Rivaroxaban or Vorapaxar, a thrombin receptor antagonist. Furthermore, FXa leaded to increased secretion of thromboxane from platelets. As conclusion this thesis could show that FXa plays a role in platelet activation. The activation is mediated by a direct activation of PAR-1 thrombin receptors on platelets. This effect can be inhibited by direct factor Xa inhibitors resulting in reduced platelet reactivity. Patients with atrial fibrillation and high cardiovascular morbidity could benefit from this effect. | |||||||
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| Lizenz: |  Urheberrechtsschutz | |||||||
| Bezug: | 2016-2018 | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 01.07.2020 | |||||||
| Dateien geändert am: | 01.07.2020 | |||||||
| Promotionsantrag am: | 03.03.2020 | |||||||
| Datum der Promotion: | 25.06.2020 |
