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

Abstract

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. 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). A total of 24 patients were enrolled in Beijing Children's Hospital from February to October 2015, all of whom were given 50IU/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 <1IU/dL within a week during prophylaxis were calculated. Baseline and the annual bleeding rate (ABR), annual joint bleeding rate (AJBR) were recorded and analyzed. The mean t1/2 of FVIII was 10.20±2.72hours and the mean time of FVIII <1IU/dL in 1week was 44.7hours (-38.56 to 102.33hours). 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 <1IU/dL in 1week (R2 =0.67 and 0.52, P<.001). 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<1IU/dL is associated with an increased rate of bleeding during prophylaxis.