Review Article
Effect of Body Weight on Dose of Vitamin K Antagonists
Abstract
Objectives: Numerous factors are well documented to affect the response to vitamin K antagonists (VKA), including dietary vitamin K, other drugs, age, pharmacogenetics, and disease states. Body weight is perhaps not as well known as a variable affecting VKA dose. Our aim was to review the literature regarding body weight and VKA dose requirements.Methods: We reviewed the English-language literature via PubMed and Scopus using the search terms VKA, warfarin, acenocoumarol, phenprocoumon, fluindione, AND body weight.
Results: Among 32 studies conducted since the widespread use of the international normalized ratio, 29 found a correlation with body weight or body surface area and VKA dose requirement. Warfarin was evaluated in 27 studies and acenocoumarol, phenprocoumon, or fluindione were assessed in 5 investigations.
Conclusions: Because of varying study methodologies, further study is warranted. Based on current evidence, clinicians should include body weight, along with other established variables when dosing VKA. Most important, obese and morbidly obese patients may require a 30% to 50% increase with the initial dosing of VKA.
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References
1. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 suppl):e44s-e88s.
2. Eccles JT. Control of warfarin therapy in the elderly. Age Ageing 1975;4:161-165.
3. Routledge PA, Chapman PH, Davies DM, et al. Factors affecting warfarin requirements. Eur J Clin Pharmacol 1979;15:319-322.
4. Kamali F, Khan TI, King BP, et al. Contribution of age, body size, and CYP2C9 genotype to anticoagulant response to warfarin. Clin Pharmacol Ther 2004;75:204-212.
5. Wallace JL, Reaves AB, Tolley EA, et al. Comparison of initial warfarin response in obese patients versus non-obese patients. J Thromb Thrombolysis 2013;36:96-101.
6. Mueller JA, Patel T, Halawa A, et al. Warfarin dosing and body mass index. Ann Pharmacother 2014;48:584-588.
7. Moffett BS, Bomgaars LR. Response to warfarin therapy in obese pediatric patients dosed according to institutional guidelines. J Pediatr Hematol Oncol 2014;36:e487-e489.
8. Yoo SH, Nah HW, Jo MW, et al. Age and body weight adjusted warfarin initiation program for ischaemic stroke patients. Eur J Neurol 2009;16:1100-1105.
9. Yoo SH, Kwon SU, Jo MW, et al. Age- and weight-adjusted warfarin initiation nomogram for ischaemic stroke patients. Eur J Neurol 2012;19:1547-1553.
10. Miao L, Yang J, Huang C, et al. Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin: proposal for a new dosing regimen in Chinese patients. Eur J Clin Pharmacol 2007;63:1135-1141.
11. Meyer zu Schwabedissen C, Mevissen V, Schmitz F, et al. Obesity is associated with a slower response to initial phenprocoumon therapy whereas CYP2C9 genotypes are not. Eur J Clin Pharmacol 2006;62:713-720.
12. Absher RK, Moore ME, Parker MH. Patient-specific factors predictive of warfarin dosage requirements. Ann Pharmacother 2002;36:1512-1517.
13. Ageno W, Steidl L, Ultori C, et al. The initial phase of oral anticoagulation with warfarin in outpatients with deep venous thrombosis. Blood Coagul Fibrinolysis 2003;14:11-14.
14. Sakaan SA, Hudson JQ, Oliphant CS, et al. Evaluation of warfarin dose requirements in patients with chronic kidney disease and end-stage renal disease. Pharmacotherapy 2014;34:695-702.
15. Shine D, Patel J, Kumar J, et al. A randomized trial of initial warfarin dosing based on simple clinical criteria. Thromb Haemost 2003;89: 297-304.
16. Jiang X, Yongxiang W, Wei Z, et al. Higher dose of warfarin for patients with pulmonary embolism complicated by obstructive sleep apnea hyponea syndrome. Heart Lung 2014;43:358-362.
17. Gage BF, Eby C, Milligan PE, et al. Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin. Thromb Haemost 2004;91:87-94.
18. Voora D, Eby C, Linder MW, et al. Prospective dosing of warfarin based on cytochrome P-450 2C9 genotype. Thromb Haemost 2005;93:700-705.
19. Gage BF, Eby C, Johnson JA, et al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther 2008;84:326-331.
20. Yoshizawa M, Hayashi H, Tashiro Y, et al. Effect of VKORC1-1639 G 9 A polymorphism, body weight, age, and serum albumin alterations on warfarin response in Japanese patients. Thromb Res 2009;124:161-166.
21. Ozer N, Cam N, Tangurek B, et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements in an adult Turkish population. Heart Vessels 2010;25:155-162.
22. Shrif NE, Won HH, Lee ST, et al. Evaluation of the effects of VKORC1 polymorphisms and haplotypes, CYP2C9 genotypes, and clinical factors on warfarin response in Sudanese patients. Eur J Clin Pharmacol 2011;67:1119-1130.
23. Schwartz JB, Kane L, Moore K, et al. Failure of pharmacogenetic-based dosing algorithms to identify older patients requiring low daily doses of warfarin. J Am Med Dir Assoc 2011;12:633-638.
24. Gu Q, Kong Y, Schneede J, et al. VKORC1-1639G 9 A, CYP2C9, EPHX1691A 9 G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China. Eur J Clin Pharmacol 2010;66:1217-1227.
25. You JH, Wong RS, Waye MM, et al. Warfarin dosing algorithm using clinical, demographic and pharmacogenetic data from Chinese patients. J Thromb Thrombolysis 2011;31:113-118.
26. Zhang W, Zhang W-J, Zhu J, et al. Genetic polymorphisms are associated with variations in warfarin maintenance dose in Han Chinese patients with venous thromboembolism. Pharmacogenomics 2012;13:309-321.
27. Zhuang W, Wen W, Xuan B, et al. Effect of CYP2C9, CYP4F2 and VKORC1 genetic polymorphisms on pharmacokinetics and pharmacodynamics of mean daily maintenance dose of warfarin in Chinese patients. Blood Coagul Fibrinolysis 2015;26:167-174.
28. Shaw K, Amstutz U, Hildebrand C, et al. VKORC1 and CYP2C9 genotypes are predictors of warfarin-related outcomes in children. Pediatr Blood Cancer 2014;61:1055-1062.
29. Momary KM, Shapiro NL, Viana MA, et al. Factors influencing warfarin dose requirements in African-Americans. Pharmacogenomics 2007;8:1535-1544.
30. Nagai R, Ohara M, Cavallari LH, et al. Factors influencing pharmacokinetics of warfarin in African-Americans: implications for pharmacogenetic dosing algorithms. Pharmacogenomics 2015;16:217-225.
31. Namazi S, Azarpira N, Hendijani F, et al. The impact of genetic polymorphisms and patient characteristics on warfarin dose requirements: a cross-sectional study in Iran. Clin Ther 2010;32:1050-1060.
32. Morin S, Bodin L, Loriot MA, et al. Pharmacogenetics of acenocoumarol pharmacodynamics. Clin Pharmacol Ther 2004;75:403-414.
33. Rathore SS, Agarwal SK, Pande S, et al. Therapeutic dosing of acenocoumarol: proposal of a population specific pharmacogenetic dosing algorithm and its validation in north Indians. PLoS One 2012;7:e37844.
34. van Schie RM, Wessels JA, Le Cessie S, et al. Loading and maintenance dose algorithms for phenprocoumon and acenocoumarol using patient characteristics and pharmacogenetic data. Eur Heart J 2011;32:1909-1917.
35. Moreau C, Pautas E, Duverlie C, et al. A model predicting fluindione dose requirement in elderly inpatients including genotypes, body weight, and amiodarone. Thromb Haemost 2014;111:705-712.
36. Ogden CL, Carroll MD, Kit BK, et al. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA 2014;311:806-808.
