Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients

Daniel Kurnik; Ronen Loebstein; Hadas Rabinovitz; Naomi Austerweil; Hillel Halkin; Shlomo Almog

doi:10.1160/TH04-06-0346

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(05): 1018-1024
DOI: 10.1160/TH04-06-0346

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Over-the-counter vitamin K₁-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K₁-depleted patients

A prospective, controlled trial

Daniel Kurnik

¹The Division of Clinical Pharmacology and Toxicology and Anticoagulation Clinic, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv University, Israel

,

Ronen Loebstein

¹The Division of Clinical Pharmacology and Toxicology and Anticoagulation Clinic, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv University, Israel

,

Hadas Rabinovitz

¹The Division of Clinical Pharmacology and Toxicology and Anticoagulation Clinic, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv University, Israel

,

Naomi Austerweil

¹The Division of Clinical Pharmacology and Toxicology and Anticoagulation Clinic, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv University, Israel

,

Hillel Halkin

¹The Division of Clinical Pharmacology and Toxicology and Anticoagulation Clinic, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv University, Israel

,

Shlomo Almog

¹The Division of Clinical Pharmacology and Toxicology and Anticoagulation Clinic, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv University, Israel

› Author Affiliations

Abstract

Summary

Most multivitamin supplements contain far less vitamin K₁ than thought to affect warfarin anticoagulation. Having described 3 patients with multivitamin-warfarin interactions, we hypothesized that vitamin K₁–depleted patients are sensitive to even small increments. Therefore, we compared the effect of a vitamin K₁-containing multivitamin on warfarin anticoagulation between patients with low versus normal vitamin K₁ status. We screened 102 warfarin-treated patients and recruited nine with “low” (< 1.5 mcg/L, 10^th percentile) (group 1) and 7 with “normal” (>4.5 mcg/L, median) (group 2) total vitamin K₁ plasma levels (vitamin K₁ + vitamin K₁ 2,3-epoxide). Patients received one multivitamin tablet containing 25 mcg of vitamin K₁ daily, for 4 weeks (period 1). A predefined algorithm was used to adjust warfarin doses if the INR was outside the therapeutic range. Patients requiring warfarin increments were then switched to 4 weeks of a vitamin K₁-free multivitamin supplement (period 2). During period 1, subtherapeutic INRs occurred in 9/9 and 1/7 patients in group 1 and 2, respectively (p <0.001). In group 1, INR decreased by a median of 0.51 (p <0.01), and warfarin dose had to be raised by 5.3% (p <0.01), whereas INR and warfarin dose did not change significantly in group 2. During period 2 (7 patients), there were trends towards decreased total vitamin K₁ and rising INRs associated with significantly lower warfarin doses. We conclude that vitamin K₁-containing multivitamins reduce INR in patients with low vitamin K₁ status. Our study suggests that vitamin Kdepleted patients are sensitive to even small changes in vitamin K₁ intake.

Keywords

Clinical trials - oral anticoagulants - vitamin K-dependent factors - clinical / epidemiological studies

Full Text

References

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