Break‐through bleeding in relation to pharmacokinetics of Factor VIII in paediatric patients with severe haemophilia A

INTRODUCTION: As the pharmacokinetics (PK) of factor VIII (FVIII) is individualized in children with haemophilia A (HA), PK parameters may be indicators of patients' bleeding phenotype and instruction for their personalized replacement program. AIM: The aim of this study was to investigate the possible relationship between PK/FVIII level and bleeding frequency in Chinese paediatric patients with severe (HA). METHODS: A total of 24 patients were enrolled in Beijing Children's Hospital from February to October 2015, all of whom were given 50 IU/kg of FVIII concentrates after a 72-hours washout period. Samples' activities (FVIII:C) were tested at 5 time points, using WinNonlin software for PK testing, and then the individual half-life(t1/2 ) and the time (h) of FVIII concentrations <1 IU/dL within a week during prophylaxis were calculated. Baseline and the annual bleeding rate (ABR), annual joint bleeding rate (AJBR) were recorded and analyzed. RESULTS: The mean t1/2 of FVIII was 10.20 ± 2.72 hours and the mean time of FVIII <1 IU/dL in 1 week was 44.7 hours (-38.56 to 102.33 hours). A significant relationship between t1/2 of FVIII and ABR0 /AJBR0 (baseline bleeding) was found (R2  = 0.75 and 0.62, P < .001). Besides, baseline and the annual bleeding rate during prophylactic treatment of haemophilia had a positive correlation with the time (hours) of FVIII <1 IU/dL in 1 week (R2  = 0.67 and 0.52, P < .001). CONCLUSION: t1/2 was an important indicator to prevent bleeding in severe HA; the frequency of bleeding will be reduced with the increased of t1/2 of FVIII. The data also demonstrates that increasing the time with a FVIII<1 IU/dL is associated with an increased rate of bleeding during prophylaxis.