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
