scholarly journals Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement

Blood ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. 861-867 ◽  
Author(s):  
Caroline Moreau ◽  
Fanny Bajolle ◽  
Virginie Siguret ◽  
Dominique Lasne ◽  
Jean-Louis Golmard ◽  
...  
Keyword(s):  
Vitamin K ◽  
Dose Response ◽  
Maintenance Dose ◽  
Vitamin K Antagonists ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Individual Variability ◽  
Dose Requirement ◽  
Warfarin Dose Requirement ◽  
Main Determinants

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.

The effects of CYP2C9 and VKORC1 gene polymorphisms on warfarin maintenance dose in Turkish cardiac patients

2020 ◽  
Author(s):  
Cansu Selcan Akdeniz ◽  
Mehtap Cevik ◽  
Ismail Polat Canbolat ◽  
Selen Yurdakul ◽  
Penbe Cagatay ◽  
...  
Keyword(s):  
Warfarin Dose ◽  
Individual Variability ◽  
Considerable Proportion ◽  
Wild Type ◽  
Dose Requirement ◽  
Study Results ◽  
Warfarin Dose Requirement ◽  
Turkish Patients ◽  
Vkorc1 Gene ◽  
Warfarin Maintenance Dose

Aim: Our aim was to examine the effect of CYP2C9 and VKORC1 polymorphisms on warfarin dose requirements in Turkish patients. Materials & methods: 24 warfarin prescribed patients were included and analyzed for eight VKORC1 and 6 CYP2C9 polymorphisms in the study. Results: Patients with CYP2C9 *1/*1 and VKORC1 -1639 GG and GA genotypes required higher warfarin doses in comparison to wild type VKORC1 genotype. Patients with CYP2C9 *1/*3 and VKORC1 -1639 GG genotypes simultaneously, required the lowest dose of warfarin (4.64 mg/day). Patients with CYP2C9 *1/*1 and VKORC1 9041 AA genotype were found to require higher warfarin doses. Conclusion: Our results provide additional evidence to support the hypothesis that CYP2C9 *2, *3, VKORC1 9041 G > A polymorphisms explain considerable proportion of inter-individual variability in warfarin dose requirement.

scholarly journals CYP2C9 Mutation Affecting the Individual Variability of Warfarin Dose Requirement

2012 ◽  
Vol 36 (6) ◽  
pp. 857 ◽  
Author(s):  
Young Bum Kim ◽  
Moon Ju Ko ◽  
Dae Gu Lee ◽  
Jong Gul Do ◽  
Ji Hye Hwang
Keyword(s):  
Warfarin Dose ◽  
Individual Variability ◽  
Dose Requirement ◽  
Warfarin Dose Requirement ◽  
The Individual

A Probable Interaction between Warfarin and the Antiretroviral TRIO Study Regimen

2012 ◽  
Vol 46 (11) ◽  
pp. e34-e34 ◽  
Author(s):  
Michelle D Liedtke ◽  
Amulya Vanguri ◽  
R Chris Rathbun
Keyword(s):  
Drug Interaction ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Dose Requirement ◽  
Vein Thrombosis ◽  
Warfarin Dose Requirement ◽  
Recurrent Deep Vein Thrombosis ◽  
The Mean ◽  
Deep Vein ◽  
Probable Interaction

OBJECTIVE: To report a probable drug interaction between the antiretroviral TRIO regimen (ritonavir-boosted darunavir, etravirine, and raltegravir) and warfarin in an HIV-infected patient. CASE SUMMARY: In January 2010, a 50-year-old transgender female with HIV infection and recurrent deep vein thrombosis began treatment with the TRIO study regimen. Treatment had been maintained with warfarin for the past 5 years and emtricitabine monotherapy for the preceding 22 months. Emtricitabine was discontinued when the TRIO regimen was started. The mean weekly warfarin dose while the patient was receiving emtricitabine monotherapy was 13.3 mg (95% CI 12.7 to 13.8), with a mean international normalized ratio (INR) of 2.8 (95% CI 2.5 to 3.1). Following the initiation of the TRIO regimen, the mean weekly warfarin dose was increased to 19.3 mg (95% CI 18.5 to 20.1) and was maintained over the ensuing 71 weeks with a mean INR of 2.6 (95% CI 2.2 to 3.0). DISCUSSION: Information on the effect of newer antiretrovirals on warfarin metabolism, as well as the collective contribution of combination antiretroviral therapy including multiple agents that may alter warfarin metabolism, is limited. We predicted that warfarin dose requirements would change upon initiation of the TRIO regimen. Given the variability in INR that can occur with chronic warfarin treatment, weekly warfarin doses were averaged during emtricitabine monotherapy (90 weeks) and TRIO regimen (71 weeks) periods. Mean weekly warfarin doses increased by 45% (p < 0.001) following initiation of the TRIO regimen. Mean INR results for the 2 time periods were not significantly different, demonstrating that stable anticoagulation was maintained. The Horn drug interaction probability scale score to assess causation indicated a probable interaction. CONCLUSIONS: An increased weekly warfarin dose requirement is predicted when warfarin is used concurrently with the antiretroviral TRIO regimen. Increased INR monitoring is prudent when the combination is administered.

The Influence of Ethnicity on Warfarin Dosage Requirement

2005 ◽  
Vol 39 (6) ◽  
pp. 1008-1012 ◽  
Author(s):  
Mai-Trang N Dang ◽  
Julie Hambleton ◽  
Steven R Kayser
Keyword(s):  
Asian American ◽  
Repeated Measures ◽  
Maintenance Dose ◽  
Demographic Data ◽  
Warfarin Dose ◽  
Optimal Dose ◽  
Warfarin Dosage ◽  
Inclusion Criteria ◽  
Dose Requirement ◽  
Warfarin Dose Requirement

BACKGROUND: The optimal dose of warfarin varies among individuals, and the prediction of a maintenance dose is difficult. Ethnicity has been reported to influence warfarin dosing. OBJECTIVE: To quantitate the influence of ethnicity on warfarin dose requirement. METHODS: We conducted a retrospective cohort study at a university anticoagulation clinic to evaluate the influence of ethnicity on warfarin dose. Inclusion criteria included age ⩾18 years, target international normalized ratio (INR) 2–3, and warfarin management within the clinic for ⩾3 months with a minimum of 5 clinic visits. We collected clinical and demographic data including age, gender, weight, ethnicity, disease states, concomitant medications, indication, weekly warfarin dosage, and INR. To assess potential confounders, multivariate, repeated-measures regression analysis was used to identify and adjust for variables that may influence the maintenance dose of warfarin. RESULTS: Of the 345 patients who met the inclusion criteria, 27% were Asian American, 6% Hispanic, 54% white, and 14% African American. The adjusted mean (95% CI) weekly warfarin doses for patients with an INR goal of 2 to 3 were Asian Americans 24 mg (21 to 27), Hispanics 31 mg (25 to 37), whites 36 mg (34 to 39), and African Americans 43 mg (39 to 47) (p < 0.001). Additional factors found to influence warfarin dose requirement included age, weight, concomitant use of amiodarone, and diagnosis of venous thromboembolism. CONCLUSIONS: Warfarin dose requirements vary across ethnic groups even when adjusted for confounding factors, suggesting that genetic variation contributes to interpatient variability.

scholarly journals Factors influencing vitamin K antagonists therapy / Factori care influențează terapia cu antagoniști ai vitaminei K

2015 ◽  
Vol 23 (2) ◽  
Author(s):  
Ioana Brudașcă
Keyword(s):  
Vitamin K ◽  
Genetic Factors ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Individual Variability ◽  
Response To Therapy ◽  
Anticoagulant Effect ◽  
Individual Response ◽  
Dose Requirement ◽  
Factors Influencing

AbstractVitamin K antagonists (VKAs) are widely used for the primary and secondary prevention of thromboembolism, their anticoagulant effect being monitored through INR. Achieving and maintaining a stable anticoagulation status is challenging, because of the narrow therapeutic range, and of the extremely variable individual response to therapy.Environmental factors such as age, gender, body mass, diet, herbal supplements, drugs, pre-existing pathology, as well as genetic factors can substantially influence the anticoagulant effect of VKAs. The main genetic factors that contribute to individual variability in response to VKAs are genetic polymorphisms in genes influencing VKAs’ metabolism (CYP2C9) and pharmacodynamic response (VKOR1) and account for about one third in the variation of warfarin and analogues dose requirement. Systematic genotyping of patients requiring warfarin therapy is still a matter of debate.Although novel oral anticoagulants (direct thrombin and factor Xa inhibitors) seem promising, VKAs are still frequently prescribed, therefore physicians should be aware of the various factors influencing VKAs’ effect, and educational programmes for doctors and patients should be conducted in that respect

Effect of CYP2C9 *11/*11 genotype on initial and long-term warfarin dose requirement and therapeutic response

2020 ◽  
Vol 21 (18) ◽  
pp. 1271-1277
Author(s):  
Alison LH Quinn ◽  
Shubha Bhat ◽  
James C Lee
Keyword(s):  
Therapeutic Response ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Term Treatment ◽  
Dose Requirement ◽  
Long Term Treatment ◽  
Warfarin Dose Requirement ◽  
Short And Long Term ◽  
Load Dose

The warfarin dose requirement and therapeutic response of a 42-year-old African–American male with genotype CYP2C9 *11/*11, VKORC1 -1639GG and CYP4F2 433Val/Val anticoagulated for ischemic stroke is described herein. Warfarin was dosed according to the institution’s personalized medicine program recommendations of a 10 mg mini-load dose, followed by dose decreases to 4–6 mg/day through discharge. Stable international normalized ratio was achieved after eight doses, with good overall long-term maintenance of therapeutic international normalized ratio over several years with warfarin doses of 3.1–4.3 mg/day. This case report sheds further light on the clinical impact of CYP2C9 *11/*11 on warfarin dose requirements, short- and long-term treatment response and practical considerations for warfarin management in suspected carriers of rare variant CYP2C9 alleles.

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