Pharmacokinetic Studies of Factor VIII in Chinese Boys with Severe Hemophilia A: A Single-Center Study
Zhen-Ping Chen1, Pei-Jing Li1, Gang Li1, Ling Tang1, Ying-Zi Zhen1, Xin-Yi Wu1, Xiao-Ling Cheng1, Koon Hung Luke2, Victor S Blanchette3, Man-Chiu Poon4, Qiu-Lan Ding5, Run-Hui Wu1
1 Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Beijing 100045, China
2 Department of Pediatrics and Laboratory Medicine, and Hemophilia Clinic, Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, K1H 8L1, Canada
3 Department of Pediatrics and Child Health Evaluative Sciences, Division of Hematology/Oncology, Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, M5G 1X8, Canada
4 Department of Medicine, Pediatrics and Oncology, and Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, University of Calgary, Foothills Hospital and Calgary Health Region, Calgary, Alberta, T2N2T9, Canada
5 Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045
Source of Support: None, Conflict of Interest: None
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 (t1/2) 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 (R2 = 0.32, P < 0.01). The t1/2of FVIII increased by 0.59 h per year. Besides age, von Willebrand factor antigen (VWF:Ag) also was associated with FVIII half-life (R2 = 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 (R2 = 0.21, P < 0.01) and VWF:Ag level (R2 = 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.