Immune Tolerance with a High Purity Plasma Derived Factor VIII Containing Von Willebrand Factor in Haemophilia A Patients with High Responding Inhibitors.

We report on 8 patients with severe haemophilia A and high responding anti-factor VIII (FVIII) inhibiting antibody in whom immune tolerance (IIT) was induced with a high purity plasma derived FVIII containing 14 to 20 IU/ml of von Willebrand factor (VWF) as a stabiliser. Their median ages at the diagnosis of the inhibitor was 10.6 months and ranged from 5 months to 9 years. At the onset of IIT, the median age was 1 year and 9 months and ranged from 9 months to 24.5 years. The median cumulative exposure days (CED) was 18.5 days and varied from 8 to 81 days when inhibitor was detected. The maximum level of inhibitor reached from 10 to 500 Bethesda Units (BU) with a median of 22.5 BU. Before inhibitor diagnosis 6 patients had received plasma derived high purity FVIII and 2 had received recombinant FVIII. The treatment schedule started with 50 IU/kg to 200 IU/kg FVIII every day. The time to reach an inhibitor level <1 BU was available for 5 patients; its median was 142 days and varied from 75 to 216 days. The treatment was considered successful when either the recovery or the half life of FVIII was normalized. The outcome was successful in 7 out of the 8 patients (87.5 %) who are now receiving FVIII concentrates either on demand or prophylactically. The last patient was considered as a partial success since the titre of his inhibitor was 0.8 BU and he could be treated by FVIII concentrates when needed. No definite IIT failure was observed in this cohort of patients. Since all the patients are by now back to FVIII treatment we can consider having a 100% success in IIT in this small cohort of patients. Therefore, despite the size of our cohort of patients, our study shows that high purity FVIII stabilized by VWF is an effective drug for the eradication of anti-FVIII inhibitors through induction of immune tolerance.

Patients data