Pharmacokinetic Studies of Factor VIII in Chinese Boys with Severe Hemophilia A: A Single-Center Study

BACKGROUND: Although much attention has been paid to the pharmacokinetics (PKs) of different factor VIII (FVIII) concentrates in persons with hemophilia A (HA), limited information is available in young boys with severe HA. In this study, we aimed to assess the PK parameters of FVIII products in boys with severe HA in China. METHODS: A total of 36 boys (plasma-derived [pd]-FVIII, n = 15; recombinant [r] FVIII, n = 21) were enrolled between January 2015 and May 2016 in Beijing Children's Hospital. PK characteristics of FVIII products were studied according to a reduced 4-sampling time point design (1 h, 9 h, 24 h, and 48 h postinfusion). RESULTS: The mean FVIII half-life (t(1/2)) was 10.99 ± 3.45 h (range 5.52–20.02 h), the mean in vivo recovery (IVR) was 2.01 ± 0.42 IU/dl per IU/kg (range 1.24–3.02 IU/dl per IU/kg) and mean clearance (CL) of FVIII is 4.34 ± 1.58 ml·kg(−1)·h(−1) (range 2.29–7.90 ml·kg(−1)·h(−1)). We also analyzed the influence of several parameters that potentially modulate FVIII PK. The age was closely associated with FVIII half-life (R(2)= 0.32, P < 0.01). The t(1/2) of FVIII increased by 0.59 h per year. Besides age, von Willebrand factor antigen (VWF:Ag) also was associated with FVIII half-life (R(2)= 0.52, P < 0.01). Patients with blood Group O had a shorter FVIII half-life than patients with non-O blood group (9.40 ± 0.68 h vs. 12.3 ± 0.79 h, t = 2.70, P = 0.01). The FVIII IVR correlated with age (R(2)= 0.21, P < 0.01) and VWF:Ag level (R(2)= 0.28, P < 0.01). CL rates were faster in young patients and in those with low-VWF:Ag levels. CL rates of FVIII are higher in blood Group O versus non-blood Group O persons (5.02 ± 0.38 vs. 4.00 ± 0.32 ml·kg(−1)·h(−1), t = 2.53, P = 0.02). CONCLUSIONS: Chinese boys with severe HA have similar PK values to other ethnic groups and large differences in FVIII PK between individual patients. Age, blood group, and VWF:Ag levels are important determining factors for FVIII CL.