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?

Question

Accepted Answer

C. Warfarin. ## 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.

Answer

A. Aspirin

Answer

B. Fondaparinux

Answer

D. Clopidogrel

Explanation

Factor V Leiden and Thrombophilia Management

Anticoagulation Strategy in Inherited Thrombophilia

Clinical Decision-Making

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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