机构：[1]Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, Beijing, China医技科室药学部首都医科大学附属北京儿童医院[2]Hematology Oncology Center, Beijing Children’s Hospital, Capital Medical University, Beijing, China医技科室职能科室临床流行病与循证医学中心血液中心首都医科大学附属北京儿童医院
IntroductionAs 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. AimThe aim of this study was to investigate the possible relationship between PK/FVIII level and bleeding frequency in Chinese paediatric patients with severe (HA). MethodsA 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(t(1/2)) 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. ResultsThe mean t(1/2) of FVIII was 10.202.72hours and the mean time of FVIII <1IU/dL in 1week was 44.7hours (-38.56 to 102.33hours). 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 <1IU/dL in 1week (R-2=0.67 and 0.52, P<.001). Conclusiont(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<1IU/dL is associated with an increased rate of bleeding during prophylaxis.
基金：
Capital Health Research and Development of special [2014-2-2092]; Beijing Municipal Administration of Hospitals Clinical medicine Development [ZY201404]; BAXTER Investigator Initiated Research Agreement [CHN-BS-IIS-2014-024]; Bayer Investigator Initiated Research Agreement [18761]
第一作者机构：[1]Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, Beijing, China
通讯作者：
通讯机构：[1]Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, Beijing, China[2]Hematology Oncology Center, Beijing Children’s Hospital, Capital Medical University, Beijing, China[*1]Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, Beijing, China.[*2]Hematology Oncology Center, Beijing Children’s Hospital, Capital Medical University, Beijing, China.
推荐引用方式(GB/T 7714)：
Cheng X.,Li P.,Chen Z.,et al.Break-through bleeding in relation to pharmacokinetics of Factor VIII in paediatric patients with severe haemophilia A[J].HAEMOPHILIA.2018,24(1):120-125.doi:10.1111/hae.13373.
APA：
Cheng, X.,Li, P.,Chen, Z.,Zhang, N.,Zhen, Y....&Wu, R..(2018).Break-through bleeding in relation to pharmacokinetics of Factor VIII in paediatric patients with severe haemophilia A.HAEMOPHILIA,24,(1)
MLA：
Cheng, X.,et al."Break-through bleeding in relation to pharmacokinetics of Factor VIII in paediatric patients with severe haemophilia A".HAEMOPHILIA 24..1(2018):120-125
