Warfarin
USMLE Step 1Difficulty: easyLast updated:
A 71-year-old man with a mechanical mitral valve takes a long-term oral anticoagulant that requires INR monitoring. He presents with melena and an INR of 8.9. Bleeding stops after he receives intravenous vitamin K and four-factor prothrombin complex concentrate.
Which of the following best describes the mechanism of action of his anticoagulant?
Answer and explanation
Correct answer: C. Inhibition of vitamin K regeneration, reducing functional factors II, VII, IX, and X
An oral anticoagulant monitored by INR and reversed with vitamin K and prothrombin complex concentrate is warfarin. The source states that warfarin is a vitamin K antagonist. It inhibits regeneration of the active form of vitamin K and therefore blocks production of functional vitamin K–dependent clotting factors II, VII, IX, and X, as well as the anticoagulant proteins C and S. These factors bind phospholipid surfaces through calcium bridges in order to function. Giving vitamin K restores synthesis of functional factors over hours. Prothrombin complex concentrate replaces the deficient factors immediately, which is why both are used for serious bleeding. Direct oral anticoagulants (thrombin or factor Xa inhibitors) do not need routine INR monitoring and are not reversed by vitamin K. Warfarin is also the agent used for mechanical heart valves.
Each option explained
- A. Direct inhibition of factor XaIncorrect. Direct factor Xa inhibition (apixaban, rivaroxaban) does not need INR monitoring and is not reversed by vitamin K.
- B. Potentiation of antithrombin activityIncorrect. Potentiation of antithrombin is the mechanism of heparins, which are given parenterally.
- C. Inhibition of vitamin K regeneration, reducing functional factors II, VII, IX, and XCorrect. Warfarin blocks regeneration of active vitamin K, so functional factors II, VII, IX, and X (and proteins C and S) are not produced.
- D. Irreversible inhibition of platelet cyclooxygenase-1Incorrect. Irreversible COX-1 inhibition is the antiplatelet mechanism of aspirin.
- E. Direct inhibition of thrombinIncorrect. Direct thrombin inhibition is the mechanism of dabigatran and argatroban, which are not monitored by INR or reversed by vitamin K.
Key point
Warfarin is a vitamin K antagonist that reduces functional factors II, VII, IX, and X (and proteins C and S); it is reversed with vitamin K plus PCC.
From the source
“It inhibits regeneration of the active form of vitamin K and, therefore, inhibits generation of functional forms of the vitamin K–dependent clotting factors II, VII, IX, and X (as well as proteins C and S).”