Influence of Vitamin D Status on the Maintenance Dose of Warfarin in Patients Receiving Chronic Warfarin Therapy

INTRODUCTION: Considering the anticoagulant actions of vitamin D, we hypothesize that vitamin D status might affect the required dose of warfarin for maintaining the therapeutic international normalized ratio (INR). METHODS: In a retrospective single-center cohort study, serum levels of 25-hydroxyvitamin D were assessed for 89 subjects receiving a stable dose of warfarin for 3 months or longer and had a stable INR between 2 and 3.5 for at least three consecutive visits. A warfarin sensitivity index (WSI), defined as the steady-state INR divided by the mean daily warfarin dose, was used for measuring the warfarin dose response. The relation between the serum level of 25-hydroxyvitamin D and WSI value and the difference in the mean WSI value between the subjects with different vitamin D status categories (sufficient, insufficient, and deficient) were assessed. RESULTS: Twenty-one subjects had vitamin D deficiency, 43 had vitamin D insufficiency, and only 25 had normal levels of 25-hydroxyvitamin D. Based on the multiple linear regression analysis, there was a significant but weakly positive correlation between WSI and 25-hydroxyvitamin D serum levels, as the value of WSI increases by almost 0.0027434 for every unit increase in 25-hydroxyvitamin D serum level (p value = 0.041). Using one-way ANOVA analysis, there was a trend in a significant difference between the groups with different vitamin D status categories regarding the mean WSI value (F = 2.95, p value = 0.057), as subjects with sufficient vitamin D state compared to those with vitamin D deficiency had a higher WSI value. CONCLUSIONS: Although the study’s limitations limit our ability to draw definite conclusions, the present data suggest that in addition to other traditional factors, vitamin D status might also affect warfarin sensitivity and maintenance dose requirement. However, to more clearly explain this link, further studies with high involvement subjects are required.