Erworbene Hämophilie infolge Antikörperbildung gegen Faktor VIII

Zusammenfassung

Die erworbene Hämophilie wird durch Bildung von Autoantikörpern verursacht, die am häufigsten gegen Faktor VIII (FVIII) gerichtet sind. Die mit erheblicher Morbidität sowie Mortalität assoziierte Erkrankung tritt bevorzugt im hohen Alter auf. Die Autoantikörper bedingen einen Aktivitätsverlust von FVIII, es kommt vorwiegend zu Weichteil-, subkutanen oder Muskelblutungen.

Diagnose: Diagnostisch führend sind verlängerte aPTT und erniedrigte Einzelfaktorkonzentration. Die FVIII-Restaktivität sowie der Hemmkörpertiter sind jedoch weniger aussagekräftig bzgl. Blutungsneigung als bei angeborener Hämophilie mit Hemmkörperbildung.

Therapie: Stillung akuter Blutungen und langfristige Hemmkörpereradikation. Bewährt hat sich der Einsatz von rekombinantem FVIIa sowie ggf. hochdosierter FVIII-Gaben oder aktivierter Prothrombinkomplexkonzentrate zur Blutstillung. Therapeutische Konzepte mit Immunsuppressiva, ggf. kombiniert mit FVIII-Gabe, oder die Immunadsorption dienen der dauerhaften Hemmkörperelimination. Da CD4⁺-T-Zellen, aber auch antiidiotypische Antikörper pathogenetisch zunehmend bedeutsam werden, dürften neue immunmodulatorische Substanzen helfen, die Therapie weiter zu verbessern.

Summary

The acquired haemophilia is caused by formation of autoantibodies which are most frequently directed against factor VIII (FVIII). This disease associated with considerable morbidity as well as mortality occurs preferentially in the elderly. The antibodies lead to a loss of FVIII activity resulting in bleeds especially of soft or subcutaneous tissue or in muscles.

Diagnosis: aPTT prolongation and the reduction of the factor activity are of diagnostic importance. However, with repect to bleeding tendency basal activity and inhibitor titre are less meaningful than in inherited haemophilia complicated by inhibitor formation.

Therapy is subdivided into treatment of acute bleeds and long-term eradication of the inhibitor. Administration of recombinant FVIIa, high dosed FVIII or activated prothrombin complex concentrates represent approved treatment options of bleeding episodes. Immunosuppressive agents occasionally combined with FVIII administration or immunoadsorption may lead to long-term inhibitor eradication. As CD4⁺ T-cells as well as anti-idiotypic antibodies appear to be increasingly pathogenetically meaningful new immunomodulating agents might improve the treatment of acquired haemophilia.

Schlüsselwörter

Erworbene Hämophilie - Faktor-VIII-Inhibitoren - Autoimmunerkrankung

Keywords

Acquired haemophilia - factor VIII inhibitors - autoimmune disease

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