Practising Haematologist Belarussian Research Centre for Paediatric Oncology, Haematology and Immunology Minsk, Minskaya Voblasts', Belarus
Background: Prophylaxis with FVIII at a standardised dose is the standard of care for people with severe haemophilia A. However, there is increasing interest in personalised prophylactic dosing regimens based on individual pharmacokinetic parameters.
Aims: To investigate the potential of dose optimisation based on the time to reach FVIII activity of 1% in children with severe haemophilia A on FVIII prophylaxis.
Methods: Data were analysed for 41 patients (aged 4–16 years) included in the Belarus Register of Patients with Congenital Clotting Disorders who had received regular prophylaxis with the plasma-derived FVIII concentrate octanate® over a two-year period. The prophylactic regimen was up to 50 IU/kg over a fixed time interval (48, 72 or 96 h). A pharmacokinetic assessment was performed on the day of administration of the scheduled prophylactic octanate® dose.
Results: Four groups were defined based on the dosing interval and the presence or absence of bleeding episodes (BEs; spontaneous or associated with increased physical activity) in the previous year (Table 1). The estimated time to 1% FVIII activity for children on a 72-h dosing interval was 78 h in those with no previous BEs (Group 1) and 70 h in those with previous BEs (Group 2). For patients on a 96-h dosing interval, the values were 116 h in children without previous BEs (Group 3) and 111 h in those with previous BEs (Group 4). The time to 1% FVIII activity was longer than the dosing interval for children in Groups 1, 3 and 4, suggesting that the dose could be decreased, whereas it was shorter than the dosing interval for children in Group 2, suggesting that the dose should be increased in these patients.
Conclusion(s): Determination of time to 1% FVIII could be considered to optimise the dosing of octanate® prophylaxis in patients with haemophilia A.
