Hamostaseologie 2019; 39(S 01): S1-S92
DOI: 10.1055/s-0039-1680165
SY21 Haemophilia Inhibitors
Georg Thieme Verlag KG Stuttgart · New York

Successful Immune Tolerance Induction in Two Patients with Severe Haemophilia B with Inhibitors and Anaphylaxis

R. Klamroth
1   Vivantes Klinikum im Friedrichshain, Innere Medizin - Angiologie und Hämostaseologie, Berlin, Germany
,
C. Kubicek-Hofmann
1   Vivantes Klinikum im Friedrichshain, Innere Medizin - Angiologie und Hämostaseologie, Berlin, Germany
,
S. Gottstein
1   Vivantes Klinikum im Friedrichshain, Innere Medizin - Angiologie und Hämostaseologie, Berlin, Germany
,
C. Köngs
2   Universitätsklinikum Frankfurt, Frankfurt/Main, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
13 February 2019 (online)

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    Introduction: There are several protocols of immune tolerance induction (ITI) using high doses of factor IX (FIX) in combination with immunosuppression in patients with severe haemophilia B (HB) with limited success rate. Very little information is available on ITI with rFIX-Fc and on the FIX-specific antibody population before and during ITI.

    Methods: The clinical charts of 2 patients who underwent ITI with rFIX-Fc were reviewed. FIX levels and inhibitor titer were recorded. The FIX specific antibody population was analyzed by ELISA including Ig isotypes and IgG subclasses.

    Results: Two brothers from Iraq (4 and 9 years old) with severe HB who developed an inhibitor after replacement with plasma-derived FIX and with history of severe anaphylactic reactions underwent a first course of ITI at our center. Immunosuppression was started with Rituximab, Mycophenolat-Mofetil (MMF) and prednisolone and they received rFIX-Fc 100 IU/kg bodyweight 3x/week. A port-a-cath was inserted only in the younger brother due to bad venous access.

    After the 5th ED to rFIX-Fc the inhibitor titer boosted in both patients up to 53 and 128 BU with severe anaphylactic reactions. This required an additional dose of Rituximab and prednisolone i.v. before the next rFIX-Fc infusions. After 20 EDs rFIX-Fc was well tolerated by both brothers without further anaphylactic reactions and no need for pretreatment with prednisolone. The inhibitor titer (Bethesda assay) was negative after 2 months in both patients achieving measurable FIX levels. MMF was stopped after 12 and 15 months. At the moment both patients are on a prophylactic regimen with rFIX-Fc 100 IU/kg BW twice weekly without any spontaneous bleeding. Both patients showed a FIX specific immune response as expected. FIX-specific IgG was positive. The Immune response was almost exclusively IgG4 driven in one brother and IgG4 and IgG1 driven in the other. FIX-specific IgA, IgM and IgE were negative in all samples tested.

    Conclusion: Two young haemophilia B patients with inhibitors and history of anaphylactic reactions achieved immune tolerance after combined immunosuppression and rFIX-Fc three times weekly.


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    No conflict of interest has been declared by the author(s).