饮食维生素K对华法林抗凝稳定性的影响

doi:10.12092/j.issn.1009-2501.2020.06.014

摘要/Abstract

摘要： 饮食维生素K摄入量的变化是造成口服华法林患者国际标准化比值(INR)异常波动的主要原因之一。对于口服华法林患者应该如何摄入维生素K,临床医师给出的意见一直比较模糊。过去许多患者被告知应“限制或避免食用富含维生素K的食物,包括绿叶蔬菜类”,这可能导致他们的维生素K摄入量偏低。近年来的研究和循证医学证据表明,华法林抗凝稳定性差与低维生素K摄入量有关;稳定保持较高水平的维生素K日摄入量(>100 μg/d)可降低无法解释的华法林剂量-反应关系个体内变异发生率,减少INR的异常波动,提高抗凝治疗的稳定性。

关键词: 华法林, 饮食维生素K, 国际标准化比值, 稳定性

Abstract: Change in dietary vitamin K intake is one of the main causes of abnormal fluctuations in international standardized ratio (INR) of patients on warfarin therapy. Advice from clinicians on how to manage vitamin K intake for patients has been vague. In the past, patients were often told to restrict or avoid vitamin K-rich foods including leafy greens during anticoagulation therapy, which could lead to lower vitamin K intake. Evidence-based studies in recent years have found that instability of warfarin therapy is associated with low intake of vitamin K. A stable and relatively higher daily intake of vitamin K (>100 μg/d) can reduce unexplained intra-individual variability in response to warfarin, and thus reduce abnormal fluctuations in INR and improve the stability of anticoagulation therapy.

Key words: warfarin, dietary vitamin K, international normalized ratio, stability

中图分类号:

R54
R969.3

翟宇, 杨劲. 饮食维生素K对华法林抗凝稳定性的影响[J]. 中国临床药理学与治疗学, 2020, 25(6): 709-715.

ZHAI Yu, YANG Jin. Effects of dietary vitamin K on the stability of warfarin anticoagulation therapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(6): 709-715.

参考文献 40

[1]	中华医学会心血管病学分会, 中国老年学学会心脑血管病专业委员会. 华法林抗凝治疗的中国专家共识 [J]. 中华内科杂志, 2013, 52(1): 76-82.
[2]	Poller L. International Normalized Ratios (INR): the first 20 years [J]. J Thromb Haemost, 2004, 2(6): 849-860.
[3]	Jones C, Pollit V, Fitzmaurice D, et al. The management of atrial fibrillation: summary of updated NICE guidance [J]. BMJ, 2014, 348: g3655.
[4]	Chan PH, Li WH, Hai JJ, et al. Time in therapeutic range and percentage of international normalized ratio in the therapeutic range as a measure of quality of anticoagulation control in patients with atrial fibrillation[J]. Can J Cardiol, 2016, 32(10): 1247.e23-1247.e28.
[5]	杨瑞, 许海沙, 张赞玲, 等. 药物相互作用对华法林抗凝强度的影响分析[J].中国临床药理学与治疗学, 2017, 22(12): 1426-1431.
[6]	Lurie Y, Loebstein R, Kurnik D, et al. Warfarin and vitamin K intake in the era of pharmacogenetics [J]. Br J Clin Pharmacol, 2010, 70(2): 164-170.
[7]	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 [J]. Chest, 2012, 141(2 Suppl): e44S-88S.
[8]	Keeling D, Baglin T, Tait C, et al. Guidelines on oral anticoagulation with warfarin-Fourth edition [J]. Br J Haematol, 2011, 154(3): 311-324.
[9]	Leblanc C, Dubé MP, Presse N, et al. Avoidance of vitamin K-rich foods is common among warfarin users and translates into lower usual vitamin K intakes [J]. J Acad Nutr Diet, 2016, 116(6): 1000-1007.
[10]	Kim KH, Choi WS, Lee JH, et al. Relationship between dietary vitamin K intake and the stability of anticoagulation effect in patients taking long-term warfarin[J]. Thromb Haemost, 2010, 104(4): 755-759.
[11]	Lubetsky A, Dekel-Stern E, Chetrit A, et al. Vitamin K intake and sensitivity to warfarin in patients consuming regular diets [J]. Thromb Haemost, 1999, 81(3): 396-399.
[12]	Khan T, Wynne H, Wood P, et al. Dietary vitamin K influences intra-individual variability in anticoagulant response to warfarin [J]. Br J Haematol, 2004, 124(3): 348-354.
[13]	Sconce E, Khan T, Mason J, et al. Patients with unstable control have a poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation [J]. Thromb Haemost, 2005, 93(5): 872-875.
[14]	Kim YE, Woo HI, On YK, et al. High intra- and inter-individual variability of plasma vitamin K concentrations in patients with atrial fibrillation under warfarin therapy[J]. Eur J Clin Nutr, 2015, 69(6): 703-706.
[15]	Rombouts EK, Rosendaal FR, van der Meer FJ. Influence of dietary vitamin K intake on subtherapeutic oral anticoagulant therapy [J]. Br J Haematol, 2010, 149(4): 598-605.
[16]	Rombouts EK, Rosendaal FR, van der Meer FJ. Daily vitamin K supplementation improves anticoagulant stability [J]. J Thromb Haemost, 2007, 5(10): 2043-2048.
[17]	Boonyawat K, Wang L, Lazo-Langner A, et al. The effect of low-dose oral vitamin K supplementation on INR stability in patients receiving warfarin. A randomised trial [J]. Thromb Haemost, 2016, 116(3): 480-485.
[18]	姜仲卓. 饮食中维生素K与华法林抗凝治疗稳定性的研究[J]. 中国医师进修杂志, 2012, 35(25): 53-54.
[19]	Gebuis EP, Rosendaal FR, van Meegen E, et al. Vitamin K1 supplementation to improve the stability of anticoagulation therapy with vitamin K antagonists: a dose-finding study [J]. Haematologica, 2011, 96(4): 583-589.
[20]	Shearer MJ, Newman P. Metabolism and cell biology of vitamin K [J]. Thromb Haemost, 2008, 100(4): 530-547.
[21]	Wallin R, Hutson SM. Warfarin and the vitamin K-dependent γ-carboxylation system [J]. Trends Mol Med, 2004, 10(7): 299-302.
[22]	Booth SL, Sadowski JA, Pennington JAT. Phylloquinone (vitamin K1) content of foods in the U.S. food and drug administration's total diet study [J]. J Agric Food Chem, 1995, 43(6): 1574-1579.
[23]	Shearer MJ, Bolton-Smith C. The UK food data-base for vitamin K and why we need it [J]. Food Chem, 2000, 68(2): 213-218.
[24]	Ferland G, Sadowski JA. Vitamin K1 (phylloquinone) content of green vegetables: effects of plant maturation and geographical growth location [J]. J Agric Food Chem, 1992, 40(10): 1874-1877.
[25]	Taylor JR, Wilt VM. Probable antagonism of warfarin by green tea [J]. Ann Pharmacother, 1999, 33(4): 426-428.
[26]	Conly JM, Stein K. Quantitative and qualitative measurements of K vitamins in human intestinal contents [J]. Am J Gastroenterol, 1992, 87(3): 311-316.
[27]	Gijsbers BL, Jie KS, Vermeer C. Effect of food composition on vitamin K absorption in human volunteers [J]. Br J Nutr, 1996, 76(2): 223-229.
[28]	Thane CW, Wang LY, Coward WA. Plasma phylloquinone (vitamin K1) concentration and its relationship to intake in British adults aged 19-64 years [J]. Br J Nutr, 2006, 96(6): 1116-1124.
[29]	McKeown NM, Jacques PF, Gundberg CM, et al. Dietary and nondietary determinants of vitamin K biochemical measures in men and women [J]. J Nutr, 2002, 132(6): 1329-1334.
[30]	Booth SL, Suttie J. Dietary intake and adequacy of vitamin K1 [J]. J Nutr, 1998, 128(5): 785-788.
[31]	National Research Council. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc [M]. Washington, DC: The National Academies Press, 2001.
[32]	中国营养学会. 中国居民膳食参考摄入量 [M]. 北京: 中国轻工业出版社, 2013.
[33]	Bingham SA, Gill C, Welch A, et al. Comparison of dietary assessment methods in nutritional epidemiology: weighed records v. 24 h recalls, food-frequency questionnaires and estimated-diet records [J]. Br J Nutr, 1994, 72(4): 619-643.
[34]	Thane CW, Bolton-Smith C, Coward WA. Comparative dietary intake and sources of phylloquinone (vitamin K1) among British adults in 1986-7 and 2000-1[J]. Br J Nutr, 2006, 96(6): 1105-1115.
[35]	Thane CW, Paul AA, Bates CJ, et al. Intake and sources of phylloquinone (vitamin K1): variation with socio-demographic and lifestyle factors in a national sample of British elderly people [J]. Br J Nutr, 2002, 87(6): 605-613.
[36]	Kamao M, Suhara Y, Tsugawa N, et al. Vitamin K content of foods and dietary vitamin K intake in Japanese young women [J]. J Nutr Sci Vitaminol, 2007, 53(6): 464-470.
[37]	周波, 王晓红, 王松涛, 等. 老年人膳食维生素K1摄入量及其主要来源[J]. 现代预防医学, 2004, 31(4): 473-474.
[38]	Baker JW, Pierce KL, Ryals CA. INR goal attainment and oral anticoagulation knowledge of patients enrolled in an anticoagulation clinic in a Veterans Affairs medical center [J]. J Manag Care Pharm, 2011, 17(2): 133-142.
[39]	Presse N, Kergoat MJ, Ferland G. High usual dietary vitamin K intake is associated with low relative variability in vitamin K intake: implications for anticoagulant therapy [J]. Br J Haematol, 2011, 153(1): 129-143.
[40]	Keeling D, Baglin T, Tait C, et al. Guidelines on oral anticoagulation with warfarin-fourth edition [J]. Br J Haematol, 2011, 154(3): 311-324.