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Break‐through bleeding in relation to pharmacokinetics of Factor VIII in paediatric patients with severe haemophilia A
Author(s) -
Cheng X.,
Li P.,
Chen Z.,
Zhang N.,
Zhen Y.,
Zhao L.,
Wang X.,
Wu R.
Publication year - 2018
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.13373
Subject(s) - medicine , haemophilia , haemophilia a , pharmacokinetics , haemophilia b , pediatrics , gastroenterology
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. Aim 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 ). Methods A total of 24 patients were enrolled in Beijing Children's Hospital from February to October 2015, all of whom were given 50 IU /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 <1 IU / dL within a week during prophylaxis were calculated. Baseline and the annual bleeding rate ( ABR ), annual joint bleeding rate ( AJBR ) were recorded and analyzed. Results The mean t 1/2 of FVIII was 10.20 ± 2.72 hours and the mean time of FVIII <1 IU / dL in 1 week was 44.7 hours (−38.56 to 102.33 hours). 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 <1 IU / dL in 1 week ( R 2 = 0.67 and 0.52, P < .001). Conclusion t 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 < 1 IU / dL is associated with an increased rate of bleeding during prophylaxis.