After cardiac surgery (eg, Fontan repair, valve replacement), children are at an increased risk of thrombosis and therefore long-term oral anti-coagulation is essential to prevent morbidity and mortality. Warfarin is commonly used, but optimising the dose and maintaining a therapeutic INR is challenging for clinicians due to considerable inter- and intra-individual variability in its pharmacokinetics (PK) and pharmacodynamics (PD). The PK/PD is affected by both patient related (such as genetic polymorphisms of the metabolic enzymes) and environmental (eg, diet) factors. To improve the accuracy and consistency of warfarin dosing, a novel PK/PD (pharmacological) based model incorporating pharmacogenomics has been developed to assist clinicians in predicting initial and maintenance warfarin doses in post-operative cardiac children.¹

The aim of the study is to compare warfarin dose management using pharmacological model with the traditional, ‘trial and error’ approach. The study is prospective and observational and involves 2 groups: In Group 1 (warfarin naïve) patients, loading and maintenance warfarin doses are estimated using the pharmacological model over 6 month duration and compared to historical case matched controls dosed according to the traditional approach. Group 2 patients already established on maintenance warfarin therapy entered a randomised cross-over study comparing pharmacological model-estimated dose adjustments with the traditional approach, over a 12 month period. The study also seeks to explore the views of children, parents and medical staff about the new model based approach.

The study commenced in October 2015 and recruitment stopped in December 2016. Group 1 (n=5) and Group 2 (n=29) participants are currently being followed up for their warfarin dosing and monitoring.

Reference

1. Hamberg A-K, Friberg LE, Hanséus K,et al. Warfarin dose prediction in children using pharmacometric bridging—comparison with published pharmacogenetic dosing algorithms. Eur J ClinPharmacol2013;69:1275–1283.