Successful low dose immune tolerance induction in severe haemophilia A with inhibitors below 40 Bethesda Units.
Different regimens are used to achieve immune tolerance in patients with severe haemophilia A and inhibitory allo-antibodies against factor VIII (FVIII). In this study, results of 26 years of low dose immune tolerance induction are evaluated. We evaluated 21 patients, who were treated with regular infusions of low dose FVIII (25-50 IU kg(-1) every other day or three times a week) to obtain immune tolerance. Several risk factors for success rate and time to success were analysed. In 18 of 21 patients (86%) immune tolerance induction (ITI) was successful. The median of the maximum inhibitor titre before start of ITI was 4.5 BU mL(-1). Success rate was associated with both a pre-ITI titre and a maximum titre during ITI below 40 BU mL(-1) (P = 0.003). The time to success was significantly shorter if the maximum inhibitor level during ITI was below 40 BU mL(-1) (P = 0.040). In low titre inhibitors (<5 BU mL(-1)) this effect was even stronger (P = 0.033). Low dose immune tolerance induction therapy was successful in severe haemophilia A patients with a pre-ITI titre below 40 BU mL(-1). The time to success is predicted by a maximum ITI titre below 40 BU mL(-1), and is even shorter in low titre inhibitors (<5 BU mL(-1)). We suggest that all patients with severe haemophilia A and a pre-ITI inhibitor titre below 5 BU mL(-1), should be treated with low dose immune tolerance induction therapy. Patients with a maximum titre below 40 BU mL(-1) may also strongly benefit from the beneficial effects of low dose immune tolerance induction therapy.
Ter Avest
P C
PC
Department Clinical Chemistry and Haematology, Van Creveldkliniek, Utrecht, The Netherlands.
Fischer
K
K
Gouw
S C
SC
Van Dijk
K
K
Mauser-Bunschoten
E P
EP
D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood*; D002648:Child; D005169:Factor VIII / Q000008:administration & dosage / Q000276:immunology*; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
D019774:Blood Coagulation Factor Inhibitors; D005169:Factor VIII