Results in three Australian haemophilia B patients with high‐responding inhibitors treated with the Malmö model

Abstract

Development of inhibitors to factor IX (F IX) is a serious complication of the treatment of patients with severe haemophilia B. Three Australian haemophilia B patients, a 22-year-old man and two 5-year-old identical twins, with high-responding inhibitors and resistant to treatment, were admitted to the centre in Malmö, Sweden, for tolerance induction according to the Malmö treatment model. This tratment consists of a combination of cyclophosphamide, F VIII of F IX, and high-dose intravenous IgG. Extracorporeal adsorption to protein A in columns, which is included in the protocol when the inhibitor titre is high at the start of treatment, had to be perforemed in the case of the twin brothers. High-purity F IX concentrates were used. The tolerance inductin was successful in the 22-year-old man and in one of the twins; they been toleant for 4 and 2 years, respectively, and are now on a home-treatment programme taking 30-40 IU F IX/kg twice weekly. These patients have no demonstrable coagulation inhibitory antibodies and in vivo reovery and half-life of infused F IX are normal. In the other twin it has not been possible to induce tolerance, though after removal of the antibodies by protein A adsorpation it is possible to achieve significant circulalting levels of F IX for 8-10 days.

Tolerance induction using the Malmö treatment model 1982–1995

“…This case has been described in detail earlier [14]. The variation in hydration during the extracorporeal treatment can give headache as a mild form of adverse event.…”

“…If the administration of factor concentrates is continued, the inhibitor ®nally disappears in several cases [14,20]. If the administration of factor concentrates is continued, the inhibitor ®nally disappears in several cases [14,20].…”

Malmö International Brother Study (MIBS): An International Survey of Brother Pairs with Haemophilia

“…As of July, 1997, fourteen centres have replied and from only one of these centres were no haemophilic brother pairs reported 1 . Data concerning 178 pairs have accrued (143 haemophilia A and 35 haemophilia B).…”

Continuous infusion of factor IX concentrate to induce immune tolerance in two patients with Haemophilia B

“…2 was born in 1986. He had previously been treated according to the Malmö protocol without success [1]. On entering the present course of treatment the inhibitor level was 5 BU mL −1 and inhibitor adsorption with protein A could therefore be omitted ( Fig.…”

“…The development of inhibitors to factors VIII/IX constitutes a severe problem for both the patient and doctor. The frequency with which inhibitors to factor IX occur in Haemophilia B seems to be lower than that to factor VIII in Haemophilia A [1, 2]. Consequently, the number of Haemophilia patients with inhibitor is much smaller than for Haemophilia A, which is also a more common disorder.…”