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Semin Thromb Hemost 2013; 39(07): 767-771
DOI: 10.1055/s-0033-1356574
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Challenges in the Management of Hemophilia B with Inhibitor

Angelika Batorova
1   Department of Hematology and Transfusion Medicine, National Hemophilia Center, University Hospital, Bratislava, Slovakia
,
Anna Morongova
1   Department of Hematology and Transfusion Medicine, National Hemophilia Center, University Hospital, Bratislava, Slovakia
,
Giuseppe Tagariello
2   Haemophilia Centre and Haematology Department, Castelfranco Veneto Hospital, Castelfranco Veneto (TV), Italy
,
Denisa Jankovicova
1   Department of Hematology and Transfusion Medicine, National Hemophilia Center, University Hospital, Bratislava, Slovakia
,
Tatiana Prigancova
1   Department of Hematology and Transfusion Medicine, National Hemophilia Center, University Hospital, Bratislava, Slovakia
,
Julia Horakova
3   Department of Hematological Oncology and Bone Marrow Transplantation, Children's University Hospital, Bratislava, Slovakia
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Publikationsverlauf

Publikationsdatum:
10. September 2013 (online)

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Abstract

Development of factor IX (FIX) inhibitor is a rare but challenging complication in hemophilia B. In addition to inefficacy of specific replacement therapy, FIX inhibitors increase morbidity due to serious allergic reactions/anaphylaxis upon treatment with FIX. Limited experience with immune tolerance induction (ITI) shows a high risk of nephrotic syndrome development and poor ITI outcomes. Recently, immunomodulation therapy has been used in ITI regimens in hemophilia B; however, relevant guidelines for ITI in hemophilia B are still lacking. We describe a 7-year-old hemophilia B patient with “null” mutation Arg29 stop who underwent surgery and massive transfusion therapy in the neonatal period and developed an FIX inhibitor after consecutive 20 exposures to FIX concentrate. At the age of 6 years, a high-dose ITI was commenced combined with immunomodulation therapy including rituximab, dexamethasone, and intravenous immunoglobulin. Allergic reactions that occurred in the third week of ITI were resolved by premedication with antihistamines and continued immunomodulation protocol without any need for ITI interruption. Inhibitor was negative from week 10; however, doses of FIX continued unchanged until pharmacokinetic criteria for success were met at month 9 of ITI. One year after the start of ITI, the patient started regular prophylaxis with FIX 41 IU/kg three times a week. No further allergic reactions or any signs of nephrotic syndrome have occurred.

Keywords

hemophilia B - FIX inhibitor - allergic reactions - immune tolerance induction - immunomodulation therapy - rituximab
 

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