ABSTRACT
INTRODUCTION: Given the qualitative differences in the role of VKORC1 and CYP2C9 polymorphisms in Vitamin K antagonists (VKA) dosing variation between adults and children, we were interested in determining at what age these polymorphism begin to play a more significant role. METHODS: A prospective cohort study of 190 patients aged 1-86years receiving VKA for treatment of venous thromboembolism. Blood samples were collected beyond the acute thrombotic event when patients were on stable targeted INR (2-3) for plasma testing and VKORC1/CYP2C9 genotyping. Patient demographics including VKA dose were collected. Simple and multiple linear regression was used to assess the relationship of VKA dose with polymorphisms and weight, adjusted for quality of anticoagulation (INR, D-Dimer), liver (AST, ALT) and renal function. RESULTS: In subjects 1-19years of age, weight explained 39.0% of dosing variation with VKORC1 and CYP2C9 playing a minor role. In contrast, in subjects 20-40years weight contributed 23%, VKORC1 44% and CYPC29 49% of the VKA dose variation. CONCLUSION: Until the age of 19, weight has a far greater effect on VKA dosing variation than VKORC1 and CYP2C9 polymorphisms. During the age of 20-40years, VKORC1 and CYP2C9 play a significant role.
Subject(s)
Anticoagulants/therapeutic use , Cytochrome P-450 CYP2C9/genetics , Polymorphism, Genetic , Venous Thromboembolism/drug therapy , Vitamin K Epoxide Reductases/genetics , Vitamin K/antagonists & inhibitors , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Anticoagulants/administration & dosage , Child , Child, Preschool , Drug Dosage Calculations , Female , Genotype , Humans , Infant , Male , Middle Aged , Prospective Studies , Venous Thromboembolism/genetics , Young AdultABSTRACT
UNLABELLED: The risk of thromboembolic events (TE) is increased by acquired or inherited thrombophilias (IT). We know that some hormonal contraceptives also increase the risk of thrombosis, thus, the use of such contraceptives are discussed as contraindications in women with IT. TEs are infrequent events in children and adolescents and in the majority of cases are associated with secondary complications from underlying chronic illness. Although adolescents are not typically considered to be at high-risk for TE, this cohort is frequently using hormonal contraception, leading to an increased risk in cases with unknown IT. The risk of TE with pregnancy alone is higher than associated with combined hormonal contraception. Progestin-only methods have not been found to increase the risk of TE with only moderate changes of coagulation proteins compared to normal reference values. CONCLUSION: Thrombophilic women are good candidates for progestin-only contraceptive methods.