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

Zhen-ping Chen; Pei-jing LI; Gang LI; Ling Tang; Ying-zi Zhen; Xin-yi WU; Xiao-ling Cheng; Koon Hung Luke; Victor S Blanchette; Man-chiu Poon; Qiu-lan Ding; Run-hui WU

Return

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

Author: Zhen-Ping CHEN ¹ ; Pei-Jing LI ¹ ; Gang LI ¹ ; Ling TANG ¹ ; Ying-Zi ZHEN ¹ ; Xin-Yi WU ¹ ; Xiao-Ling CHENG ¹ ; Koon Hung LUKE ² ; Victor S BLANCHETTE ³ ; Man-Chiu POON ⁴ ; Qiu-Lan DING ⁵ ; Run-Hui WU ¹
Author Information

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.
Publication Type:Journal Article
Keywords: Boys; Factor VIII; Hemophilia A; Pharmacokinetics
MeSH: Adolescent; Blood Coagulation Tests; Child; Child, Preschool; China; Factor VIII; pharmacokinetics; Hemophilia A; drug therapy; Humans; Male; von Willebrand Factor
From: Chinese Medical Journal 2018;131(15):1780-1785
CountryChina
Language:English
Abstract:
BackgroundAlthough 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.
MethodsA 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).
ResultsThe mean FVIII half-life (t) 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·h (range 2.29-7.90 ml·kg·h). We also analyzed the influence of several parameters that potentially modulate FVIII PK. The age was closely associated with FVIII half-life (R = 0.32, P < 0.01). The tof FVIII increased by 0.59 h per year. Besides age, von Willebrand factor antigen (VWF:Ag) also was associated with FVIII half-life (R = 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 = 0.21, P < 0.01) and VWF:Ag level (R = 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·h, t = 2.53, P = 0.02).
ConclusionsChinese 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.