Perioperatives Management und Therapie von Blutungskomplikationen

Zusammenfassung

Die neuen oralen Antikoagulanzien (DOAK) hemmen direkt Thrombin (Dabigatran, Pradaxa®) bzw. den aktivierten Faktor X (Rivaroxaban, Xarelto® und Apixaban, Eliquis®) und sind für die Thromboembolieprophylaxe nach Hüft- und Kniegelenksersatzoperationen und die Schlaganfallsprophylaxe bei nicht-valvulärem Vorhofflimmern zugelassen. Weitere Indikationen bestehen für Rivaroxaban (Xarelto) in der Behandlung der tiefen Bein-Venenthrombose, der Prävention der Lungenarterienembolie und der Antikoagulation nach Myokardinfarkt. Edoxaban (Lixiana®) erwartet als direkter FXa-Inhibitor seine Zulassung in Deutschland für die Indikation nicht valvuläres Vorhofflimmern im Jahr 2014. Bei vergleichbaren Halbwertszeiten von 8-17 Stunden erfolgt die Elimination für Dabigatran (Pradaxa) und Rivaroxaban (Xarelto) überwiegend renal, für Apixaban (Eliquis) zu 75% hepatisch und für Edoxaban (Lixiana®) zu 40% renal und zu 60% über die Faeces. Das Pausieren der direkten Antikoagulanzien vor einer Operation oder Intervention ist primär von der Nieren- bzw. Leberfunktion des Patienten bzw. dem Blutungsrisiko der Operation abhängig. Gegenüber den Vitamin K-Antagonisten Phenprocoumon (Marcumar®, Falithrom®) und Warfarin (Coumadin®) ist allgemein von kürzeren präoperativen Pausierungszeiten auszugehen. Für den Fall der akuten Blutung wird für den direkten Thrombininhibitor Dabigatran (Pradaxa) die Hämodialyse zur Elimination der Substanz empfohlen. Für die direkten FXa-Inhibitoren Rivaroxaban (Xarelto) und Apixaban (Eliquis) ist dies aufgrund der hohen Plasmaeiweißbindung nicht möglich. Für Edoxaban (Lixiana) sind hierzu keine Daten bekannt. Supportiv wird bei lebensbedrohlichen Blutungen die Substitution von Prothrombinkomplexpräparat (PPSB), welches die Faktoren II, VII, IX und X enthält, und in zweiter Linie die Gabe von aktivierten Faktorenkonzentraten wie rekombinanter aktivierter Faktor VII und aktiviertem Prothrombinkomplexpräparat empfohlen.

Summary

The new oral anticoagulants directly inhibit either thrombin (Dabigatran, Pradaxa®,) or activated Factor X (rivaroxaban, Xarelto®, and apixaban, Eliquis®) and have been approved for thromboprophylaxis after hip and knee replacement surgery and stroke prevention in non-valvular atrial fibrillation. Moreover, rivaroxaban has been approved for the treatment of deep venous thrombosis, prevention of pulmonary embolism and anticoagulation after acute myocardial infarction. The direct FXa-inhibitor edoxaban (Lixiana®) expects approval for the prevention of stroke in atrial fibrillation in Germany in 2014. The half lives of all direct anticoagulants range between 8 and 17 hours. Dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) are mainly excreted by the kidneys, apixaban (Eliquis®) by the liver (75%) and edoxaban (Lixiana®) by the kidneys (40%) and the faeces in 60%. Prior to surgery a shorter cessation is expected compared to the vitamin k antagonists phenprocoumon (Marcumar®, Falithrom®) and warfarin (Coumadin®). For acute bleedings caused by the direct thrombin inhibitor dabigatran (Pradaxa®) hemodialysis is recommended to eliminate the drug from the plasma. Due to the high protein binding the direkt FXa-inhibitors rivaroxaban (Xarelto®) and apixaban (Eliquis®) can not be hemodialysed. For edoxaban (Lixiana®) no data on elimination by renal replacement therapy are available. In case of life-threatening bleeding the replacement of a prothrombin complex preparation (PCC) containing the factors II, VII, IX and X and, second line, activated factor concentrates as recombinant factor VIIa or activated prothrombin complex preparations are recommended.

Kernaussagen

• Bei der perioperativen Planung sind die Halbwertszeiten der direkten oralen Antikoagulanzien (DOAK) und das Vorliegen einer Nieren- oder Leberinsuffizienz entscheidend.

• In Zulassungstudien zeigen die DOAK bisher keine erhöhte, sondern tendenziell eine niedrigere Inzidenz von Blutungen als Warfarin.

• Das Blutungsrisiko hängt neben operationsspezifischen Aspekten von der Pharmakokinetik der Substanz sowie der Nieren- und Leberfunktion ab.

• Bei aktiver Blutung unter DOAK ist der Einsatz von Aktivkohle bei 2–3 h zurückliegender Einnahme von DOAK noch sinnvoll; eine Magenspülung zeigt wahrscheinlich – wenn überhaupt – nur innerhalb der ersten Stunde nach Einnahme Wirkung. Zu Frischplasma und Tranexamsäure ist beim gegenwärtigen Forschungsstand keine eindeutige Aussage möglich.

• Derzeit liegt für keines der zugelassenen DOAK ein direktes und spezifisches Antidot vor. Gegeben werden können nur Gerinnungsfaktorenkonzentrate zur Substitution. Dabei ist jedoch eine hämostaseologische Beratung dringend zu empfehlen.

Schlüsselwörter:

Blutungskomplikationen - neue direkte orale Antikoagulanzien - Dabigatran - Apixaban - Edoxaban - Rivaroxaban

Key words:

new oral anticoagulants - bleeding complications - dabigatran - apixaban - edoxaban - rivaroxaban

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