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Management von intrazerebralen Blutungen unter oraler Antikoagulation

Management of oral anticoagulation related intracerebral hemorrhage

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Zusammenfassung

Die Inzidenz der intrazerebralen Blutung (ICB) unter oraler Antikoagulation (OAK) wird mit dem demographischen Wandel weiter zunehmen. Die OAK-ICB ist gekennzeichnet durch größere Blutungsvolumina, häufigere Hämatomprogression und Einbruch in das Ventrikelsystem, woraus insgesamt eine schlechtere Prognose resultiert. Neben dem grundsätzlichen ICB-Akutmanagement ist eine umgehende Gerinnungsnormalisierung anzustreben. Bei ICB unter Vitamin-K-Antagonisten (VKA) sollte so schnell wie möglich eine suffiziente Antagonisierung (Ziel-INR [International Normalized Ratio]: <1,3) durch Prothrombinkomplexkonzentrate (PPSB) mit zusätzlicher Substitution von Vitamin K erfolgen. Bei ICB unter Dabigatran sollte eine umgehende Antagonisierung durch Idarucizumab stattfinden; bei ICB unter Faktor-Xa-Inhibitoren sollte, sobald zugelassen oder im Rahmen klinischer Studien, die Gabe von Andexanet, bei Nichtverfügbarkeit die hochdosierte Gabe von PPSB, erfolgen. Bezüglich des OAK-Wiederbeginns stehen Ergebnisse randomisierter Studien aus. Umfangreiche Beobachtungsstudien und Metaanalysen zeigten unter OAK-Wiederaufnahme eine verringerte Inzidenz thrombembolischer Ereignisse und Mortalität ohne gleichzeitig signifikant vermehrtes Auftreten hämorrhagischer Komplikationen. Die Verwendung von Nicht-Vitamin-K-abhängigen oralen Antikoagulanzien (NOAK) könnte weiter zur Sicherheit der OAK-Wiederaufnahme beitragen, welche bei Vorhofflimmer(VHF)-Patienten nach 4 bis 8 Wochen stattfinden sollte. Demgegenüber ist die VKA-Wiederaufnahme bei Patienten mit mechanischen Herzklappen vor Ablauf einer Woche nach ICB nicht zu empfehlen. Die Sicherheit erscheint weiter durch die ICB-Lokalisation sowie das Vorliegen von zerebralen Mikroblutungen, kortikaler oberflächlicher Siderose und kortikalen/konvexen Subarachnoidalblutungen beeinflusst, weshalb grundsätzlich eine individuelle Risikoabwägung hinsichtlich thrombembolischer versus hämorrhagischer Ereignisse notwendig ist.

Abstract

The incidence of intracerebral hemorrhage (ICH) in patients using oral anticoagulation (OAC) will continue to increase with the demographic change of an aging population. As compared to primary spontaneous ICH, OAC-ICH is characterized by larger hematoma volumes, more frequent hematoma enlargement and intraventricular hemorrhage resulting in an even worse prognosis. Specific treatment should focus on immediate reversal of anticoagulation in addition to the basic acute management of ICH. In ICH patients using vitamin K antagonists (VKA), complete anticoagulant reversal with an international normalized ratio (INR) <1.3 should be achieved as quickly as possible using prothrombin complex concentrate (PCC) with additional substitution of vitamin K. Patients with ICH under dabigatran treatment should receive idarucizumab. In ICH patients using factor-Xa inhibitors, andexanet should be administered as soon as approved in Europe or within clinical studies and if unavailable alternatively high-dose PCC administration. Regarding OAC resumption, results from randomized trials are pending. In comprehensive observational studies and meta-analyses ICH patients resuming OAC showed a reduced incidence of thromboembolic events and mortality without significantly increased rates of hemorrhagic complications. Non-vitamin K dependent oral anticoagulants (NOAC) might further increase the safety of OAC resumption, which should be initiated after 4–8 weeks for patients with atrial fibrillation. In contrast, VKA resumption in patients with mechanical heart valves should not take place earlier than 1 week after ICH. Generally, safety of OAC resumption appears to be affected by ICH localization along with the presence of cerebral microbleeding, cortical superficial siderosis and cortical/convexity subarachnoid hemorrhage, making it crucial to weigh up the individual patient risk with respect to thromboembolic versus hemorrhagic events.

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Abbreviations

CAA:

Zerebrale Amyloidangiopathie

HR:

Hazard-Ratio

ICB:

Intrazerebrale Blutung

KI:

Konfidenzintervall

NOAK:

Nicht-Vitamin-K-abhängige orale Antikoagulanzien

OAK:

Orale Antikoagulation

OR:

Odds-Ratio

PPSB:

Prothrombinkomplexkonzentrat

VHF:

Vorhofflimmern

VKA:

Vitamin-K-Antagonisten

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  1. Klinik für Neurologie, Universitätsklinikum Erlangen, Schwabachanlage 6, 91054, Erlangen, Deutschland

    J. A. Sembill, J. B. Kuramatsu & H. B. Huttner

  2. Klinik für Kardiologie, Abt. Klinische Elektrophysiologie, Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland

    S. H. Hohnloser

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J.A. Sembill, J.B. Kuramatsu, S.H. Hohnloser und H.B. Huttner geben an, dass kein Interessenkonflikt besteht.

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Sembill, J.A., Kuramatsu, J.B., Hohnloser, S.H. et al. Management von intrazerebralen Blutungen unter oraler Antikoagulation. Herz 44, 315–323 (2019). https://doi.org/10.1007/s00059-019-4802-y

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