2003; baxter - Supplements - Haematologica

76D. LillicrapTable 1. Role of factor IX genotype in anaphylaxis (Thorland,Hemophilia 1999).mutations, whereas all patients with severe missensemutations were inhibitor-free. 14,15 Interestingly,and presently unexplained, is the fact thatthe prevalence of factor IX inhibitors in theSwedish population of patients with severehemophilia B is 23%, an approximately five-foldhigher prevalence than that reported in otherpopulations.Management of factor IX inhibitorsIn the light of the severe adverse reactions experiencedby hemophilia B patients who developallo-antibodies, a good case can be made for earlygenotyping of new cases of severe hemophiliaB. These studies should most effectively proceedwith polymerase chain reaction amplification ofthe eight factor IX exons followed by sequencingof the amplicons. Failure to amplify one or severalexons is highly likely to be indicative of afactor IX deletion mutation. With currentlyavailable information, the risk of factor IXinhibitor development with a factor IX deletionmutation is between 25-50%. With a missensemutation the inhibitor risk is negligible and witha nonsense mutation the risk is probably between5-25%.If a new factor IX deletion or nonsense mutationis detected, two revisions to routine treatmentmerit consideration. Firstly, that the initial15-25 infusions of factor IX be performed in amedically supervised environment with access todrugs for the treatment of an anaphylactic reaction.The second treatment revision that deservesevaluation is either the co-administration ofpulse immunosuppressive therapy during theearly phase of factor IX administration or the useof an alternative hemostatic agent, most probablyrecombinant factor VIIa, to treat bleedingduring the first two to three years of life. If a factorIX inhibitor develops and immune toleranceinduction is attempted, careful monitoring forthe development of proteinuria should be performed.Figure 1. The factor IX geneand adjacent mcf2 proto-oncogenelocus. The extent of thirteen,partial and total factor IXgene deletion mutations isshown with documentation ofaccompanying inhibitor generation(I) or no inhibitor (NI*).haematologica vol. 88(supplement n. 12):september 2003