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

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.

2020 ◽  
pp. postgradmedj-2019-137197
Author(s):  
Maryam Hosseindokht ◽  
Hamed Zare ◽  
Rasoul Salehi ◽  
Leyla Pourgholi ◽  
Shayan Ziaee ◽  
...  

BackgroundThe optimal dose of anticoagulant warfarin varies among patients to achieve the target international normalised ratio. Although genetic variations related to warfarin pharmacokinetics and vitamin K cycle are important factors associated with warfarin dose requirements, these variations do not completely explain the large interindividual variability observed in the most populations, suggesting that additional factors may contribute to this variability. microRNAs have recently been introduced as regulators of drug function genes, and therefore, may be involved in drug responses. In this study, we aimed to evaluate the possible association between variants in the seed region of microRNAs, which target the genes involved in the action of warfarin and warfarin dose requirement.Methods526 samples were collected from Iranian patients. Four selected polymorphisms in the seed region of microRNAs (rs2910164, rs66683138, rs12416605 and rs35770269 in miR-146a, miR-3622a, miR-938 and miR-449c, respectively) were genotyped by PCR-restriction fragment length polymorphism method.Resultsrs2910164 C/G in the seed region of miR-146a was associated with warfarin dose requirement (p<0.001); the patients with GG genotype had the higher mean dose of warfarin (40.6 mg/week, compared with 33.9 and 31.8 mg/week for GC and CC genotypes, respectively). The association of other polymorphisms with warfarin dose requirement was not statistically significant.Conclusionrs2910164 C/G in the seed region of miR-146a is associated with warfarin maintenance dose, likely by disrupting interaction between miR-146a and ATP-binding cassette subfamily B member 1 gene, ABCB1. Therefore, this polymorphism may possibly be a potential factor for assessment of warfarin dose requirements.


Blood ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. 861-867 ◽  
Author(s):  
Caroline Moreau ◽  
Fanny Bajolle ◽  
Virginie Siguret ◽  
Dominique Lasne ◽  
Jean-Louis Golmard ◽  
...  

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.


2020 ◽  
Author(s):  
Cansu Selcan Akdeniz ◽  
Mehtap Cevik ◽  
Ismail Polat Canbolat ◽  
Selen Yurdakul ◽  
Penbe Cagatay ◽  
...  

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.


2019 ◽  
Vol 85 (8) ◽  
pp. 1684-1691 ◽  
Author(s):  
Tuukka A. Helin ◽  
Lotta Joutsi‐Korhonen ◽  
Heidi Asmundela ◽  
Mikko Niemi ◽  
Arto Orpana ◽  
...  

2016 ◽  
Vol 23 (7) ◽  
pp. 800-806
Author(s):  
Aisha Qayyum ◽  
Muzammil Hasan Najmi ◽  
Qaisar Mansoor ◽  
Zia-ur-Rehman Farooqi ◽  
Abdul Khaliq Naveed ◽  
...  

2010 ◽  
Vol 126 (1) ◽  
pp. 12-17 ◽  
Author(s):  
Vittorio Giuliano ◽  
Gabrio Bassotti ◽  
Evangelia Mourvaki ◽  
Danilo Castellani ◽  
Esmeralda Filippucci ◽  
...  

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