Abstract
Background/Objectives:
Vitamin K intake is considered as a controllable contributor to warfarin sensitivity. It is restricted in warfarin-treated patients. However, little study has assessed the vitamin K status in warfarin-treated patients. We directly measured plasma vitamin K in warfarin-treated patients and evaluated its effect on anticoagulation.
Subjects/Methods:
A total of 302 plasma vitamin K concentrations were assessed using high-performance liquid chromatography for 203 outpatients with atrial fibrillation under warfarin treatment. Clinical and laboratory information including warfarin dosage, plasma warfarin concentrations, prothrombin time international normalized ratio (PT INR) and CYP2C9/VKORC1 genotypes was reviewed retrospectively. The anticoagulation stability (intra-individual variability, frequency of PT INR tests and complications) was investigated in 163 patients with long-term warfarin therapy. Plasma vitamin K was measured in 40 healthy subjects and in 40 patients before and after initial warfarin treatment.
Results:
Vitamin K concentrations were significantly decreased after the initiation of warfarin treatment (before treatment: 1.72 ng/ml; after treatment: 0.59 ng/ml, P<0.05). There was a large inter-individual variability in vitamin K levels (0.2–4.2 ng/ml) in warfarin-treated patients. PT INR was more frequently checked in patients with low plasma vitamin K levels than in those with high vitamin K levels (9.5 times/year vs 7.5 times/year, P=0.029). Two patients with gross hematuria showed very low vitamin K levels (<0.4 ng/ml).
Conclusions:
We found high inter- and intra-individual variability in vitamin K concentration in warfarin-treated patients. Low vitamin K concentration in warfarin-treated patients suggested excessive dietary restriction. Plasma vitamin K measurement would be helpful for dietary control and anticoagulation stability.
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References
Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G . Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133: 160S–198S.
Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1998; 114: 445S–469S.
Loebstein R, Yonath H, Peleg D, Almog S, Rotenberg M, Lubetsky A et al. Interindividual variability in sensitivity to warfarin—Nature or nurture? Clin Pharmacol Ther 2001; 70: 159–164.
Gurwitz JH, Avorn J, Ross-Degnan D, Choodnovskiy I, Ansell J . Aging and the anticoagulant response to warfarin therapy. Ann Intern Med 1992; 116: 901–904.
O'Malley K, Stevenson IH, Ward CA, Wood AJ, Crooks J . Determinants of anticoagulant control in patients receiving warfarin. Br J Clin Pharmacol 1977; 4: 309–314.
Wells PS, Holbrook AM, Crowther NR, Hirsh J . Interactions of warfarin with drugs and food. Ann Intern Med 1994; 121: 676–683.
Vecsler M, Loebstein R, Almog S, Kurnik D, Goldman B, Halkin H et al. Combined genetic profiles of components and regulators of the vitamin K-dependent gamma-carboxylation system affect individual sensitivity to warfarin. Thromb Haemost 2006; 95: 205–211.
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: 396–399.
Udall JA . Human sources and absorption of vitamin K in relation to anticoagulation stability. JAMA 1965; 194: 127–129.
Kurnik D, Loebstein R, Rabinovitz H, Austerweil N, Halkin H, Almog S . Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients. A prospective, controlled trial. Thromb Haemost 2004; 92: 1018–1024.
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: 651–656.
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: 2682–2689.
Holmes MV, Hunt BJ, Shearer MJ . The role of dietary vitamin K in the management of oral vitamin K antagonists. Blood Rev 2012; 26: 1–14.
Kamali F, Wynne H . Pharmacogenetics of warfarin. Annu Rev Med 2010; 61: 63–75.
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: 1226–1228.
Saito R, Takeda K, Yamamoto K, Nakagawa A, Aoki H, Fujibayashi K et al. Nutri-pharmacogenomics of warfarin anticoagulation therapy: VKORC1 genotype-dependent influence of dietary vitamin K intake. J Thromb Thrombolysis 2014; 38: 105–114.
Cushman M, Booth SL, Possidente CJ, Davidson KW, Sadowski JA, Bovill EG . The association of vitamin K status with warfarin sensitivity at the onset of treatment. Br J Haematol 2001; 112: 572–577.
Pedersen FM, Hamberg O, Hess K, Ovesen L . The effect of dietary vitamin K on warfarin-induced anticoagulation. J Intern Med 1991; 229: 517–520.
Sorano GG, Biondi G, Conti M, Mameli G, Licheri D, Marongiu F . Controlled vitamin K content diet for improving the management of poorly controlled anticoagulated patients: a clinical practice proposal. Haemostasis 1993; 23: 77–82.
Thane CW, Paul AA, Bates CJ, Bolton-Smith C, Prentice A, Shearer MJ . Intake and sources of phylloquinone (vitamin K1): variation with socio-demographic and lifestyle factors in a national sample of British elderly people. Br J Nutr 2002; 87: 605–613.
Sconce E, Khan T, Mason J, Noble F, Wynne H, Kamali F . Patients with unstable control have a poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation. Thromb Haemost 2005; 93: 872–875.
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: 755–759.
Kamali F, Edwards C, Butler TJ, Wynne HA . The influence of (R)- and (S)-warfarin, vitamin K and vitamin K epoxide upon warfarin anticoagulation. Thromb Haemost 2000; 84: 39–42.
Acknowledgements
This study was supported by a grant of the Korean Health technology R&D Project, Ministry for Health & Welfare, Republic of Korea (HI13C0871).
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Kim, YE., Woo, H., On, Y. et al. High intra- and inter-individual variability of plasma vitamin K concentrations in patients with atrial fibrillation under warfarin therapy. Eur J Clin Nutr 69, 703–706 (2015). https://doi.org/10.1038/ejcn.2015.41
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DOI: https://doi.org/10.1038/ejcn.2015.41
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