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The pediatric acenocoumarol dosing algorithm: the Children Anticoagulation and Pharmacogenetics Study
H Maagdenberg1, M B Bierings2, C H van Ommen3
1Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
Journal of Thrombosis and Haemostasis : JTH
|June 24, 2018
Summary
A new pharmacogenetic dosing algorithm for acenocoumarol in children was developed. Clinical factors like body surface area and indication explained most dose variability, but adding VKORC1, CYP2C9, and CYP2C18 genotypes significantly improved prediction.
Area of Science:
- Pediatric pharmacology
- Pharmacogenetics
- Drug dosing algorithms
Background:
- Significant variability exists in vitamin K antagonist dosing requirements.
- Unlike warfarin, pediatric dosing algorithms for acenocoumarol are lacking.
- This study addresses the need for a pediatric acenocoumarol dosing algorithm.
Purpose of the Study:
- To develop dosing algorithms for pediatric acenocoumarol recipients.
- To assess the impact of genetic information on acenocoumarol dose prediction.
- To identify key clinical and genetic factors influencing acenocoumarol dosage in children.
Main Methods:
- Multicenter retrospective follow-up study of pediatric patients in the Netherlands.
- Inclusion of 175 pediatric patients treated with acenocoumarol (1995-2014).
- Genotyping for VKORC1, CYP2C9, CYP4F2, CYP2C18, and CYP3A4, alongside collection of clinical data.
Main Results:
- A clinical algorithm (body surface area, indication) explained 45.0% of acenocoumarol dose variability.
- Incorporating VKORC1, CYP2C9, and CYP2C18 genotypes increased explained variability to 61.8%.
- Clinical factors were primary drivers, but genetic factors, particularly VKORC1, contributed significantly.
Conclusions:
- Clinical factors are the most influential in determining acenocoumarol dosage in pediatric patients.
- Genetic polymorphisms in VKORC1, CYP2C9, and CYP2C18 are significant predictors of acenocoumarol dose requirements.
- The developed algorithm enhances personalized acenocoumarol dosing in children.
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