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, Inhaltsverzeichnis

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

Autor*innen

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

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

Volltext

Referenzen

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