Warfarin and vitamin K intake in the era of pharmacogenetics

Authors

  • Yael Lurie,

    1. Institute of Clinical Pharmacology and Toxicology, Chaim Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv and
    2. Clinical Pharmacology Unit, Rambam Healthcare Campus, The Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
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  • Ronen Loebstein,

    1. Institute of Clinical Pharmacology and Toxicology, Chaim Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv and
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  • Daniel Kurnik,

    1. Institute of Clinical Pharmacology and Toxicology, Chaim Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv and
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  • Shlomo Almog,

    1. Institute of Clinical Pharmacology and Toxicology, Chaim Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv and
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  • Hillel Halkin

    Corresponding author
    1. Institute of Clinical Pharmacology and Toxicology, Chaim Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv and
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Dr Hillel Halkin MD, Institute of Clinical Pharmacology and Toxicology, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
Tel.: +972 3 5302355
Fax: +972 3 5351596
E-mail: hillel.halkin@sheba.health.gov.il

Abstract

The considerable variability in the warfarin dose–response relationship between individuals, is explained mainly by genetic variation in its major metabolic (CYP2C9) and target (VKORC1) enzymes. Despite the predominance of pharmacogenetics, environmental factors also affect the pharmacokinetics and pharmacodynamics of warfarin, and are often overlooked. Among these factors, dietary and supplemental vitamin K consumption is a controllable contributor to within-, and between-patient variability of warfarin sensitivity. In this commentary we review the current role of vitamin K in warfarin anticoagulation therapy, with emphasis on the following:

1 The effect of dietary and supplemental vitamin K on warfarin anticoagulation, beyond the impact of genetic variability in CYP2C9 and VKORC1. We deal separately with the effects of vitamin K on warfarin dose requirements during the induction of therapy, as opposed to its effect on stability of anticoagulation control during maintenance therapy.

2 The role of vitamin K supplementation in warfarin treated patients with vitamin K deficiency as well as in patients with unstable warfarin anticoagulation, and

3 The role of therapeutic vitamin K in cases of warfarin over-anticoagulation.

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