Management von schwerwiegenden intrazerebralen Blutungen unter Antikoagulation

Zusammenfassung

Die Inzidenz der intrazerebralen Blutung unter oraler Antikoagulation (OAK-ICB) steigt aufgrund der demografischen Entwicklung und der daraus resultierenden Zunahme an Patienten, die bei einem Vorhofflimmern antikoaguliert werden. Die OAK-ICB stellt eine der schwerwiegendsten Formen des hämorrhagischen Schlaganfalls dar, ist charakterisiert durch größere Blutungsvolumina, vermehrten Ventrikeleinbruch sowie häufigere und prolongierte Nachblutungen. Der Einfluss dieser Prognoseparameter mündet schließlich in eine erhöhte Sterblichkeit und ein hohes Maß an bleibender funktioneller Beeinträchtigung. Doch gerade bei diesem schweren Erkrankungsbild fehlt meist eine belastbare Evidenz, sodass die aktuellen internationalen und europäischen Leitlinien häufig nur schwache Therapieempfehlungen abgeben können. Im Rahmen der Akutbehandlung einer OAK-ICB ist das Hauptziel eine Minimierung der Hämatomprogression, welche durch Blutdruck- und Gerinnungsmanagement möglicherweise erreicht werden kann. Für alle OAK-ICBs erscheint die sofortige und aggressive Blutdrucksenkung auf einen systolischen Zielwert von 140 mmHg (mind. innerhalb von 4 – 6 Stunden) nach Aufnahme sinnvoll und für intrazerebrale Blutungen unter Vitamin-K-Antagonisten konnte eine Assoziation mit einer reduzierten Nachblutungsrate aufgezeigt werden. Die Antagonisierung der OAK-ICB sollte immer so rasch wie möglich, aber in Abhängigkeit von der jeweiligen oralen Antikoagulation erfolgen. Für die Vitamin-K-Antagonisten assoziierte ICB konnten große multizentrische Arbeiten in den letzten Jahren beitragen ein präziseres Vorgehen zu definieren. In Rahmen einer deutschlandweiten Kohortenstudie an knapp 1200 OAK-ICB (unter Marcumar bzw. Falithrom) konnten erstmals konkrete Zielwerte identifiziert werden. Eine Antagonisierung sollte mindestens bis zu einem INR-Wert < 1,3 bzw. 1,2 mindestens innerhalb von 4 Stunden nach Aufnahme erfolgen. Mittel der Wahl sollten Prothrombinkomplexkonzentrate (PPSB) sein, um eine rasche und vollständige Antagonisierung zu erzielen. Durch dieses kombinierte Procedere konnte eine deutliche Minimierung der Hämatomwachstumsraten und eine reduzierte Krankenhaussterblichkeit verzeichnet werden. Seit kurzem steht für Dabigatran assoziierte Blutungen ein Antidot (Idarucizumab) zur Verfügung, welches in Studien eine rasche und nahezu vollständige Elimination sowie suffiziente Hämostase aufzeigen konnte. Für Blutungen unter Faktor Xa-Inhibitoren besteht aktuell großer Handlungsbedarf, da bislang kein Antidot verfügbar ist und es ebenso unklar ist, ob in der klinischen Praxis eine relevante Antagonisierung durch gängige Substanzen, z. B. PPSB oder gefrorenes Frischplasma (GFP) erreicht werden kann. In dieser Übersichtsarbeit liegt der Schwerpunkt auf der Akut-Behandlung einer OAK-ICB und versucht anhand der aktuellen Datenlage konkrete Behandlungsoptionen aufzuzeigen. Ferner werden gegenwärtige Studien zur intensivmedizinischen Behandlung der ICB beleuchtet, um daraus relevante Implikationen für die Therapie einer OAK-ICB abzuleiten.

Abstract

The incidence of anticoagulation associated intracerebral hemorrhage (OAC-ICH) is increasing alongside the demographic change and with patients requiring oral anticoagulation for atrial fibrillation. OAC-ICH is one of the most detrimental sub-types of hemorrhagic stroke being characterized by larger hemorrhage volumes, more frequent intraventricular hemorrhage, increased and prolonged hematoma enlargement. The impact of these outcome predictors results in greater mortality rates and larger numbers of patients left in functionally dependent states after ICH. Yet, evidence on treatment options for these severely deceased patients remains limited resulting in weak recommendations by international and European guidelines. Minimization of hematoma enlargement constitutes the main focus of acute-care, possibly achieved by blood pressure- and reversal-management. In all OAC-ICH patients irrespective of anticoagulation agent immediate and aggressive blood pressure reductions as fast as possible targeting systolic blood pressure levels of 140 mmHg (at least within 4 – 6 hours) seems reasonable. Specifically, in vitamin-k associated ICH blood pressure reductions have been shown to be associated with reduced rates of hematoma enlargement. Reversal management in any OAC-ICH should be carried out as fast as possible, though accounting for the different anticoagulation agents used. In vitamin-k associated ICH recent large-sized multicenter investigations contributed to refine reversal strategies. One German-wide cohort study including roughly 1200 patients, identified for the first time beneficial target values to guide reversal treatment. Anticoagulation reversal should achieve INR values of less than 1,3 or 1,2 at least within 4 hours after admission. Agents to be used comprise prothrombin complex concentrates (PCC) which may achieve faster and more complete reversal. This combined approach was associated with significant reductions of hematoma enlargement and lower in-hospital mortality rates. For dabigatran related bleeding complications most recently an antidote (Idarucizumab) has been approved, which has been prospectively investigated and showed rapid and almost complete elimination as well as sufficient hemostasis. Currently, bleeding under influence of factor-Xa inhibitors poses great difficulties as no antidote is available and efficacy of commonly used antagonizing agents, i. e. PCC or fresh-frozen plasma (FFP) has not been proven for clinical use. The main aim of the present review focusses on acute-care management of OAC-ICH and tries to depict treatment options according to most current data. Moreover, current neurocritical-care therapies for ICH will be reviewed to identify relevant implications specific to OAC-ICH treatment.

Schlüsselwörter

intrazerebrale Blutungen - Antikoagulation - Blutungsprogression - Blutdruckmanagement

Keywords

intracerebral hemorrhage - anticoagulation - hematoma enlargement - blood pressure reductions

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