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

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( t 1/2 ) 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 t 1/2 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 t 1/2 of FVIII and ABR 0 / AJBR 0 (baseline bleeding) was found ( R 2  = 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 ( R 2  = 0.67 and 0.52, P  <   .001). Conclusion t 1/2 was an important indicator to prevent bleeding in severe HA ; the frequency of bleeding will be reduced with the increased of t 1/2 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.