Inhibitors in factor IX deficiency a report of the ISTH‐SSC international FIX inhibitor registry (1997–2006)

Abstract

Haemophilia B is an X-linked disorder resulting in coagulation factor IX deficiency. Patients with severe deficiency (<1% factor IX activity) may have significant bleeding complications similar to patients with haemophilia A or factor VIII deficiency. The development of inhibitory antibodies to the missing coagulation factor is a major complication in patients with haemophilia. While the incidence of inhibitors in patients with haemophilia A is higher than that in haemophilia B, the occurrence of allergic and or anaphylactic reactions with the development of inhibitors is unique to haemophilia B patients. Since haemophilia B is a rare bleeding disorder and the incidence of inhibitors is an even rarer entity, a registry was established by Dr Indira Warrier under the auspices of the FVIII/FIX subcommittee of the International Society of Thrombosis and Haemostasis, to gather information on the occurrence and characteristics of patients with inhibitors and also the incidence of allergic and anaphylactic reactions in this group of patients. This is the first report from this registry and helps us to gather some insight on haemophilia B patients with inhibitors and complications related to inhibitor development and difficulties with immune tolerance.

Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial

“…1 The most serious complication of replacement therapy today is the development of neutralizing FIX antibodies (FIX inhibitors). [3][4][5][6] Nonacog beta pegol is a recombinant FIX derivative produced without human-or animal-derived materials. A 40-kDa polyethylene glycol (PEG) moiety is attached to the FIX activation peptide by site-directed glycoPEGylation.…”

Nacionalna priporočila za obravnavo bolnikov s hemofilijo

“…Manj težke alergične reakcije se lahko pojavijo tudi kasneje (208,209). Bolniki s HB s pozitivno družinsko anamnezo za razvoj inhibitorjev ali z mutacijo (odsoten gen ali velika delecija v genu za FIX), ki poveča tveganje za nastanek inhibitorjev (178), morajo v prvih 10-20 ED prejemati nadomestno terapijo v ustanovi, ki obvlada zdravljenje težkih alergičnih reakcij (208,209).…”

The current state of adverse event reporting in hemophilia

“…Specific for haemophilia B is the occurrence of allergic and anaphylactic reactions to FIX concentrate infusion occurring at time of inhibitor development [34]. The exact pathophysiologic mechanism is unclear, it occurs more frequently in patients with a large deletion in the FIX gene, but overall the incidence is low.…”