Recurrent episodes of anaphylaxis in a patient with haemophilia B: a case report.

Abstract

Haemophilia B is an X-linked disorder resulting in coagulation factor IX (FIX) deficiency that is treated with the administration of exogenous FIX obtained from plasma of healthy donors or by a DNA recombinant technique1. The development of an inhibitor antibody against exogenous FIX is a serious complication and occurs in 1–3% of patients with haemophilia B and in 25–30% of patients with haemophilia A. Interestingly, in patients with haemophilia B, inhibitor development is associated with the risk of anaphylactic reaction to FIX administration. This reaction can occur concurrently with inhibitor detection or weeks or months apart regardless of which source of FIX replacement is used, plasma or recombinant. For this reason, the guidelines recommend that the first 20 administrations of FIX concentrate should be performed in hospital1,2. Common features of patients who develop a factor IX inhibitor are occurrence of an allergic/anaphylactic reaction early in life, a high inhibitor titre (>5 Bethesda units [BU]), exposure to various types of factor IX products, and the presence of abnormalities of the factor IX gene (F9)3. Patients with complete gene deletions or rearrangements of F9 have an approximately 50% risk of inhibitor development, while those with nonsense or frame shift mutations have a risk of approximately 20%4–5. This suggests that the greater the impairment of FIX synthesis, the higher the risk of anaphylaxis, although this phenomenon may occur in patients with nonsense mutations4–6. The precise mechanism of this adverse reaction remains unclear and the various hypotheses that had been considered include extracellular distribution of the small FIX protein with potential mast cell activation7,8, complement activation by IgG1 antibody formation9, an IgE-mediated hypersensitivity response10, higher amounts of exogenous protein (the concentration of FIX is much higher than that of factor VIII)11 and the absence of tolerance to FIX in patients with mutations resulting in a complete absence of FIX production12. Moreover, in contrast to antibodies against FVIII, antibodies against FIX may form circulating immune complexes that can initiate anaphylaxis when the individual is re-exposed to FIX concentrate6. We describe a case of three anaphylactic reactions in a patient with haemophilia B after exposure to FIX of different origins.