The patient should begin daily low-dose vitamin K supplementation. In 2007, a double-blind randomized trial compared the effects of low-dose vitamin K (100-150 µg/d) and placebo on INR stability in 70 patients receiving chronic warfarin therapy. Vitamin K supplementation resulted in 19 of 35 patients achieving the predefined criteria for stable control of anticoagulation compared with only 7 of 35 patients receiving placebo. It was hypothesized that low-dose vitamin K reduced the day-to-day variation in dietary vitamin K intake in patients with unexplained INR fluctuations.

Polymorphisms in the genes transcribing enzymes involved in the metabolism of vitamin K antagonists, such as cytochrome P-450 2C9 and vitamin K epoxide reductase complex-1, contribute to the variability in dose requirements among patients but do not explain day-to-day or week-to-week INR fluctuations in individual patients. Therefore, genetic testing would not be helpful in this situation.

A factor V Leiden mutation would not explain INR fluctuations. The only thrombophilia that might cause INR fluctuations over time is the presence of a lupus anticoagulant; however, such frequent fluctuations as this patient is experiencing would not be expected with any thrombophilia. Thus, a thrombophilia evaluation would not be indicated.

Aspirin alone will not provide the same protective benefit as warfarin for this patient with recurrent deep venous thrombosis.