A 32-year-old woman presents with recurrent thrombosis in the deep veins of the lower limb. Investigations reveal activated protein C resistance and genetic testing confirms Factor V Leiden mutation. She is not currently pregnant. What is the drug of choice for long-term anticoagulation in this patient?

Explanation

## Factor V Leiden and Thrombophilia Management **Key Point:** Factor V Leiden is the most common inherited thrombophilia, causing activated protein C resistance. Patients with recurrent venous thromboembolism (VTE) require long-term anticoagulation. ### Anticoagulation Strategy in Inherited Thrombophilia **High-Yield:** Warfarin (vitamin K antagonist) is the gold standard for long-term anticoagulation in patients with inherited thrombophilias such as Factor V Leiden, particularly after a first or recurrent VTE event. | Drug | Mechanism | Role in Factor V Leiden | Duration | |------|-----------|------------------------|----------| | **Warfarin** | Vitamin K antagonist; inhibits factors II, VII, IX, X | First-line for long-term anticoagulation | Indefinite if recurrent VTE | | Aspirin | Antiplatelet; inhibits COX-1 | Insufficient for VTE prevention; arterial thrombosis only | N/A | | Clopidogrel | ADP receptor antagonist; antiplatelet | Ineffective for venous thromboembolism | N/A | | Fondaparinux | Factor Xa inhibitor; parenteral | Acute treatment bridge; not suitable for long-term monotherapy | Short-term | ### Clinical Decision-Making **Clinical Pearl:** In non-pregnant women with Factor V Leiden and recurrent VTE, warfarin with a target INR of 2–3 is preferred over DOACs (direct oral anticoagulants) in many guidelines because the evidence base for DOACs in inherited thrombophilia is less robust than for warfarin. **Mnemonic — Warfarin Indications in Thrombophilia: VIT-K** - **V**enous thromboembolism (recurrent) - **I**nherited thrombophilia (Factor V Leiden, prothrombin G20210A) - **T**ransient or provoked thrombosis (extended anticoagulation) - **K**eep INR 2–3 (target range) **Warning:** Aspirin and clopidogrel are antiplatelet agents used for *arterial* thrombosis (MI, stroke), not venous thromboembolism. They are ineffective for VTE prevention in thrombophilia. **Tip:** Fondaparinux is an acute parenteral anticoagulant used for initial treatment of VTE; it is not suitable for long-term monotherapy because of the risk of thrombocytopenia with prolonged use and lack of long-term safety data.