Reduction of Anti-FIX Inhibitor Titers in a Hemophilia B Patient with Continuous Use of FEIBA.

Background: Inhibitor formation is a severe complication of hemophilia B associated with poor response to factor replacement and uncontrolled bleeding, although an inhibitor formation in hemophilia B is a rare event compared to hemophilia A. Currently, immune tolerance is the only proven method for inhibitor eradication. However, immune tolerance induction in patients with hemophilia B is a rare occurrence. We report a case of a hemophilia B patient who had a reduction of inhibitor titer during continual use of FEIBA.

Case report: Patient is an 11-year-old boy with severe FIX deficiency and high titer inhibitor (historical peak: 65 BU/mL) since age 3 years. Since inhibitor formation, the patient had received FEIBA or FVIIa on demand. FVIIa became therapeutically not effective in 1999 October, and bleeding frequency increased as he developed a target joint. In 1999 November, 2002 February, and 2004 September, he received high dose of FIX concentrate for neutralization of inhibitor and then cyclophosphamide for 8 weeks. We achieved only a transient effect in reducing the inhibitor titer. The inhibiter titer fluctuated between 20 and 60 BU/mL. Since 2005 January, subsequently, he had received FEIBA 1,000–2,000 IU per dose (30–50 units/kg) on demand. He needed FEIBA twice or thrice a week, and continued to receive this dose till now. The inhibitor titer was gradually getting lower after a transient rise up to 39 BU/mL on 2005 February. On 2006 February, the inhibitor titer became below 1.0 BU/mL, and finally undetectable on 2006 March, despite the longevity of the inhibitor (8 years). Factor IX recovery was normalized, and bleeding frequency dramatically decreased. Elimination of the inhibitor by the continued administration of FEIBA was observed. Anaphylactic reaction and the development of nephrotic syndrome were not seen.

Conclusion: The continuing use of FEIBA safely and effectively might decrease the inhibitor titer and the frequency of bleeding episodes in hemophilia B patients. This case may provide us the optimization of the FEIBA dose, and duration of treatment for inducing tolerance by using FEIBA.