Abstract:
:Managing vitamin K antagonist (VKA) therapy is challenging in children because of a narrow therapeutic range and wide inter- and intra-individual variability in dose response. Only a few small studies have investigated the effect of nongenetic and genetic factors on the dose response to VKAs in children. In a cohort study including 118 children (median age 9 years; range, 3 months-18 years) mostly with cardiac disease, we evaluated by multivariate analysis the relative contribution of nongenetic factors and VKORC1/CYP2C9/CYP4F2 genotypes on warfarin (n = 83) or fluindione (n = 35) maintenance dose and the influence of these factors on the time spent within/above/below the range. The results showed that height, target international normalized ratio and VKORC1 and CYP2C9 genotypes were the main determinants of warfarin dose requirement, accounting for 48.1%, 4.4%, 18.2%, and 2.0% of variability, respectively, and explaining 69.7% of the variability. Our model predicted the warfarin dose within 7 mg/wk in 86.7% of patients. None of the covariates was associated with the time spent above or below the international normalized ratio range. Whether this model predicts accurately the effective maintenance dose is currently being investigated.
journal_name
Bloodjournal_title
Bloodauthors
Moreau C,Bajolle F,Siguret V,Lasne D,Golmard JL,Elie C,Beaune P,Cheurfi R,Bonnet D,Loriot MAdoi
10.1182/blood-2011-07-365502subject
Has Abstractpub_date
2012-01-19 00:00:00pages
861-7issue
3eissn
0006-4971issn
1528-0020pii
blood-2011-07-365502journal_volume
119pub_type
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