Break-through bleeding in relation to pharmacokinetics of Factor VIII in paediatric patients with severe haemophilia

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X Cheng1, P Li2, Z Chen2

  • 1Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Haemophilia : the Official Journal of the World Federation of Hemophilia
|December 2, 2017
PubMed

Insights

The half-life of factor VIII (FVIII) in children with haemophilia A is a key indicator for preventing bleeding. Longer FVIII half-life correlates with reduced bleeding frequency during prophylaxis.

Area of Science:

  • Paediatric Haematology
  • Pharmacokinetics
  • Bleeding Disorders

Background:

  • Factor VIII (FVIII) pharmacokinetics (PK) are highly individualized in children with haemophilia A (HA).
  • PK parameters may predict bleeding phenotype and guide personalized replacement therapy.
  • Understanding these individual PK variations is crucial for effective HA management.

Purpose of the Study:

  • To investigate the relationship between FVIII PK parameters and bleeding frequency in Chinese paediatric patients with severe HA.
  • To determine if FVIII levels correlate with bleeding events in this population.
  • To inform personalized prophylaxis strategies based on PK data.

Main Methods:

  • 24 Chinese paediatric patients with severe HA were enrolled.
  • Factor VIII concentrates (50 IU/kg) were administered after a washout period.
  • FVIII activity was measured at 5 time points to calculate individual half-life (t1/2) and time below 1 IU/dL weekly.
  • Baseline and annual bleeding rates (ABR, AJBR) were recorded and analyzed.

Main Results:

  • The mean FVIII half-life (t1/2) was 10.20 ± 2.72 hours.
  • A significant correlation was found between FVIII t1/2 and baseline bleeding rates (R²=0.75 for ABR0, R²=0.62 for AJBR0, P<.001).
  • Increased time with FVIII levels <1 IU/dL weekly was positively correlated with higher bleeding rates during prophylaxis (R²=0.67 for ABR, R²=0.52 for AJBR, P<.001).

Conclusions:

  • FVIII half-life (t1/2) is a critical indicator for bleeding prevention in severe HA.
  • Increased FVIII t1/2 is associated with a reduced frequency of bleeding events.
  • Maintaining FVIII levels above 1 IU/dL for longer durations is linked to decreased bleeding rates during prophylactic treatment.
Abstract

Keywords:
bleedinghaemophilia Apaediatric patientspharmacokinetics

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