Publikationsserver der Universitätsbibliothek Marburg
Titel:Die Plasma-Sensibilität auf Heparin und Enoxaparin
Autor:Ajib, Salem Abdulfatah
Weitere Beteiligte: Stief, T. (Prof. Dr.)
Veröffentlicht:2013
URI:https://archiv.ub.uni-marburg.de/diss/z2014/0033
URN: urn:nbn:de:hebis:04-z2014-00335
DOI: https://doi.org/10.17192/z2014.0033
DDC: Medizin
Titel (trans.):The Plasma Sensibility to Heparin and Enoxaparin
Publikationsdatum:2014-01-14
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Plasma, Heparin, Sensibilität, Enoxaparin, Sensibility, Heparin, Enoxaparin, Plasma

Zusammenfassung:
Unfraktioniertes Heparin (UFH) und niedermolekulares Heparin (NMH) sind die am häufigsten verwendeten klinischen Antikoagulantien zur Therapie von Patienten mit venösen Thromboembolien (VTE), akutem Koronarsyndrom (ACS) und für Thromboseprophylaxe in Krankenhäusern. Die klinische Tendenz favorisiert zunehmend NMH, auch intravenös, z.B. beim transmuralen Myokardinfarkt (STEMI). Der extrinsische Gerinnungs-Aktivitätstest (EXCA) wurde im Hauptteil der Arbeit bei 51 normalen Citratplasmen oder 213 Citratplasmen der Patienten (bei normaler PT und APTT in Abwesenheit von NMH) nach 50 μl Supplementierung mit 0-1 IU/ml UFH oder NMH durchgeführt. Der recalcifizierte Gerinnungsaktivitätstest (RECA) wurde im Nebenteil der Arbeit mit 10 normalen Citratplasmen und in 32 Citratplasmen der Patienten nach 50 μl Supplementierung mit 0-10 mIU/ml UFH oder NMH durchgeführt. 1 IU/ml Enoxaparin reduzierte die normale Thrombin-Generierung in EXCA auf etwa 13% der Norm, während bei 1 IU/ml Heparin die normale Thrombin-Generierung komplett supprimiert wurde. Dies bedeutet, dass 1 IU/ml Enoxaparin ein stark therapeutisches Antikoagulans ist, während 1 IU/ml UFH bereits im toxischen Bereich ist. 0.01 IU/ml Heparin oder Enoxaparin reduzierte die normale Thrombin-Generierung in EXCA nur um etwa 10% oder 20%. UFH bei 0.1 mIU/ml reduzierte die Thrombin-Generierung im RECA nicht, sondern erhöhte sogar die Thrombin-Generierung um etwa 20%, während 0.1 mIU/ml NMH signifikant die Thrombingenerierung um etwa 30% -60% hemmte. Dies bedeutet, dass Heparin in ultra-niedrigen Konzentrationen, wie z. B. am Ende der Heparin-Infusion, besonders für Patienten mit sensibler intrinsischer Hämostase gefährlich werden könnte. Es wird vorgeschlagen, mit NMH das Ende der Heparin-Infusion zu überbrücken oder UFH auf NMH umzustellen. Diese Ergebnisse unterstützen das Konzept, dass die Dosierung der NMHs für jeden Patienten individuell durch einen ultra-spezifischen Thrombin-Generierungstest (EXCA oder INCA (intrinsischer Gerinnungs-Aktivitätstest)) angepasst werden sollte. Die Dosierung der NMH soll individuell entsprechend dem Ziel der Antikoagulation (prophylaktisch oder therapeutisch) und dem plasmatischen Ansprechen auf das Heparin angepaßt werden. Zielaktivität für therapeutische oder prophylaktische Antikoagulation sind 10-20% oder 20-40% der normalen Trigger-induzierten Thrombin-Generierung respektiv. Die adäquate Dosierung des NMH beim individuellen Patienten sollte durch einen spezifischen Thrombin-Generierungstest kontrolliert werden.

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