Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 42-year-old man arrives for follow-up consultation. Three months ago he developed a proximal right leg deep venous thrombosis following a skiing-related fracture of the right tibia. Although not recommended by guidelines, a thrombophilia evaluation was performed, which revealed an elevated plasma homocysteine level, and subsequent genetic testing revealed that he is homozygous for the C677T methylene tetrahydrofolate reductase (MTHFR) polymorphism. He is otherwise healthy, and his medical history is unremarkable. He has a 12-year-old son. There is no family history of thrombotic disorders. His only medication is warfarin.

Which of the following is the most appropriate next step in management?

A. Folic acid and vitamin B₁₂ administration
B. Indefinite continuation of warfarin
C. MTHFR polymorphism testing of first-degree relatives
D. Warfarin discontinuation

MKSAP Answer and Critique

The correct answer is D. Warfarin discontinuation.

This patient’s warfarin should be discontinued. Patients who have experienced a single venous thromboembolism (VTE) due to a major transient risk factor only require short-term anticoagulation for 3 months. This patient experienced a deep venous thrombosis following a traumatic tibia fracture. Generally, the clinical setting of a thrombotic event (unprovoked versus provoked) provides greater prognostic information regarding recurrence risk than the results of thrombophilia testing. Therefore, in most instances, thrombophilia testing results will not influence treatment duration and testing is not indicated. If thrombophilia testing is considered, it should be targeted to persons in whom finding a strong thrombophilia may influence length of anticoagulant treatment or have an impact on other family members if they also tested positive for the higher risk thrombophilia. However, consensus is limited on what defines higher risk thrombophilias.

Elevated plasma homocysteine levels are associated with an increased risk for a first venous or arterial thromboembolic event. Homocysteine levels can be lowered with folic acid, vitamin B₆, and vitamin B₁₂. However, this does not change the risk of a first thromboembolic event, which this patient has already experienced, nor of recurrent VTE.

Homozygosity for the methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism can be associated with elevated homocysteine levels but alone is not a risk factor for VTE. Thus, no clinical indication exists for testing for the MTHFR polymorphism in patients or first-degree relatives.

Key Point

• Thrombophilia test results typically do not influence treatment duration, so testing is not indicated, especially for patients with only a single venous thromboembolism resulting from a major transient risk factor.

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