Original Article

International Normalized Ratio Response Subsequent to Modest Increase in Vitamin K Intake in Patients Treated with Warfarin

Abstract

Background: Warfarin is an effective oral anticoagulant which exert its effect by blocking the utilization of vitamin K. Warfarin therapy requires ongoing monitoring using the international normalized ratio (INR). In this study, effect of modest increase in vitamin K intake from vegetables on INR values was evaluated in warfarin treated patients.
Methods: A single-center study involving 24 outpatients (mean age, 62 years) with two last INR in therapeutic range in which INR variations was less than 0.5. Patients were selected based on their VKORC1 1639G→A polymorphism so that 8 patients from each of GG, AA or GA genotypes were recruited. Patients were asked to consume a vegetable mix (including lettuce, peeled cucumber and tomato) containing approximately 100 µg vitamin K (divided in two meals, lunch and dinner) daily for one week when INR response was measured.
Results: Daily consumption of vegetable mix decreased patient’s INR from 2.43±0.51 to 2.08± 0.46 (P<0.001). INR value had a significant decrease in each VKORC1 genotypes (from 2.55± 0.55 to 2.21± 0.54 in GG, 2.35± 0.33 to 2.00± 0.25 in AA, and  2.39± 0.65 to 2.00± 0.25 in GA) but the values did not differ between genotypes.
Conclusions: Daily increase in vegetable salad containing approximately 100 µg, decreased INR of patients. Therefore, avoiding variation in consumption of foods with even moderate content of vitamin K could help to prevent INR fluctuations in warfarin treated patients.

Oake N, Jennings A, Forster AJ, Fergusson D, Doucette S, van Walraven C. Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: a systematic review and meta-analysis. CMAJ 2008;179(3): 235-44.

Pedersen FM, Hamberg O, Hess K, Ovesen L. The effect of dietary vitamin K on warfarin-induced anticoagulation. J Intern Med 1991; 229(6): 517-20.

Wadelius M, Chen LY, Lindh JD, et al. The largest prospective warfarin- treated cohort supports genetic forecasting. Blood 2009; 113(4): 784-92.

Khan T, Wynne H, Wood P, et al. Dietary vitamin K influences intra-individual variability in anticoagulant response to warfarin. Br J Haematol 2004; 124(3): 348-54.

Schurgers LJ, Shearer MJ, Hamulyak K, Stocklin E, Vermeer C. Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose- response relationships in healthy subjects. Blood 2004; 104(9): 2682-9.

Gu Q, Kong Y, Schneede J, et al. VKORC1-1639G>A, CYP2C9, EPHX1691A>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(12): 1217-27.

Garber AK, Binkley NC, Krueger DC, Suttie JW. Comparison of phylloquinone bioavailability from food sources or a supplement in human subjects. J Nutr 1999; 129(6): 1201-3.

Franco V, Polanczyk CA, Clausell N, Rohde LE. Role of dietary vitamin K intake in chronic oral anticoagulation: prospective evidence from observational and randomized protocols. Am J Med 2004; 116(10): 651-6.

Lurie Y, Loebstein R, Kurnik D, Almog S, Halkin H. Warfarin and vitamin K intake in the era of pharmacogenetics. Br J Clin Pharmacol 2010; 70(2):164-70.

Kim KH, Choi WS, Lee JH, Lee H, Yang DH, Chae SC. Relationship between dietary vitamin K intake and the stability of anticoagulation effect in patients taking long-term warfarin. Thromb Haemost 2010; 104(4): 755-9.

Lubetsky A, Dekel-Stern E, Chetrit A, Lubin F, Halkin H. Vitamin K intake and sensitivity to warfarin in patients consuming regular diets. Thromb Haemost 1999; 81(3): 396-9.

Sconce E, Avery P, Wynne H, Kamali F. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood 2007; 109(6): 2419-23.

Couris R, Tataronis G, McCloskey W, et al. Dietary vitamin K variability affects International Normalized Ratio (INR) coagulation indices. Int J Vitam Nutr Res 2006; 76(2): 65-74.

Sconce EA, Avery PJ, Wynne HA, Kamali F. Vitamin K epoxide reductase complex subunit 1 (VKORC1 ) polymorphism influences the anticoagulation response subsequent to vitamin K intake: a pilot study. J Thromb Haemost 2008; 6(7): 1226-8.

Files
IssueVol 3, No 1-2 (Spring 2015) QRcode
SectionOriginal Article(s)
Keywords
Warfarin International Normalized Ratio Vegetables Vitamin K VKORC1

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Foroughi M, Miri R, Assarzadegan F, Nasrollahzadeh J. International Normalized Ratio Response Subsequent to Modest Increase in Vitamin K Intake in Patients Treated with Warfarin. J Pharm Care. 2016;3(1-2):3-6.