Hämostaseologie, Table of Contents

Hamostaseologie 2010; 30(S 01): S119-S121
DOI: 10.1055/s-0037-1619092

Case report

Schattauer GmbH

Immuntoleranzinduktion mit hoch dosiertem FVIII und intravenösen Immunglobulin-Pulsen

Ein Patient mit Hemmkörper-Hämophilie AImmune tolerance induction with high-dose FVIII and pulsed intravenous immunoglobulin

M. Stiefel

¹Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin, Martin-Luther-Universität Halle-Wittenberg

,

C. Pinkwart

¹Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin, Martin-Luther-Universität Halle-Wittenberg

,

R. Haase

¹Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin, Martin-Luther-Universität Halle-Wittenberg

,

N. Merkel

¹Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin, Martin-Luther-Universität Halle-Wittenberg

,

D. Forsberg

¹Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin, Martin-Luther-Universität Halle-Wittenberg

,

C. Mauz-Körholz

¹Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin, Martin-Luther-Universität Halle-Wittenberg

› Author Affiliations

Summary

The development of neutralizing allo-antibodies against factor VIII (FVIII) or FVIII inhibitors is a severe complication in the treatment of haemophilia A. About 25% of the children with severe haemophilia A develop FVIII inhibitors. Here we report on a boy with severe haemophilia A and intron 22 inversion of the FVIII gene who was diagnosed at ten months of age. After 16 exposure days to FVIII (81 days after initial exposure) he developed a FVIII inhibitor (maximum: 9.76 BU/ml). Therapy: We started immune tolerance induction (ITI) according to the Bonn protocol with high dose plasma derived FVIII concentrate (100 IU per kg body weight) twice daily. For additional inhibitor elimination treatment the patient received intravenous immunoglobulin (ivIg) at a dose of 1–2 g/kg body weight every 4 to 6 weeks. After start of treatment a rapid decline of the inhibitor level was observed, nevertheless low FVIII inhibitor levels persisted (<5 BU/ ml). Furthermore, the FVIII half-life was still accelerated. However, after every course of ivIg the inhibitor level declined and FVIII half-life was prolonged. Currently, the FVIII half-life is approaching normal values after more than seven months of ITI duration. Conclusion: Additional application of immunoglobulin is beneficial for immune tolerance induction.

Zusammenfassung

Neutralisierende Alloantikörper gegen Faktor VIII (FVIII) oder Hemmkörper sind eine schwerwiegende Komplikation in der Therapie der Hämophilie A. Etwa 25% der Patienten mit schwerer Hämophilie A sind betroffen.Wir berichten von einem Jungen, bei dem im Alter von zehn Monaten eine schwere Hämophilie A mit Intron-22-Inversion im FVIII-Gen diagnostiziert wurde. Nach 16 FVIII-Expositionstagen (81 Tage nach initialer Exposition) entwickelte er FVIII-Hemmkörper (maximaler Titer 9,76 BE/ml). Therapie: Wir begannen eine Immuntoleranzinduktion (ITI) in Anlehnung an das Bonn-Protokoll mit hochdosiertem plasmatischem FVIII (zweimal pro Tag 100 E/kg Körpergewicht). Zur zusätzlichen Inhibitorelimination erfolgten intravenöse Immunglobulingaben (1–2 g/kg Körpergewicht) alle 4–6 Wochen. Nach anfänglich raschem Abfall des Hemmkörpertiters blieb im Verlauf der Behandlung der Hemmkörper mit niedrigen Titern (<5 BE/ml) nachweisbar und die FVIII-Halbwertszeit beschleunigt. Nach Immunglobulingabe war ein Abfall des Hemmkörpers und ein Anstieg der FVIII-Halbwertszeit zu beobachten. Aktuell ist die FVIIIHalbwertszeit nahezu normalisiert nach einer ITI-Dauer von sieben Monaten. Schlussfolgerung: Zusätzliche Immunglobulingaben können die Immuntoleranztherapie unterstützen.

Keywords

Keywords

Haemophilia A - FVIII inhibitors - ivIg

Schlüsselwörter

Schlüsselwörter

Hämophilie A - FVIII-Hemmköper - ivIg

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