Warfarin

Related Subjects: Warfarin | Warfarin and Bleeding | Vitamin K (Phytomenadione)

⚠️ Important Clinical Principle: Warfarin inhibits vitamin K–dependent clotting factors II, VII, IX, X and the anticoagulant Protein C. Because Protein C has a short half-life (~8 hours), it falls first → creating a transient prothrombotic state early in therapy. This explains the risk of warfarin-induced skin necrosis and why bridging with LMWH/UFH is required when rapid anticoagulation is needed.

💊 About Warfarin

• Oral vitamin K antagonist (VKA).
• Used for treatment and prevention of thromboembolism.
• Name derived from Wisconsin Alumni Research Foundation (WARF) + “-arin”.
• Requires careful INR monitoring due to narrow therapeutic index.

🧬 Pathophysiology & Mode of Action

• Vitamin K–dependent factors: II, VII, IX, X and proteins C & S.
• Require γ-carboxylation for calcium binding and clotting activity.
• Vitamin K epoxide must be recycled by VKOR (Vitamin K epoxide reductase).
• Warfarin inhibits VKOR → reduces active vitamin K → produces non-functional clotting factors.
• Full anticoagulant effect delayed 3–5 days (depends on Factor II half-life).

📌 Indications (UK Practice)

• 🫀 Mechanical heart valves (especially mitral position).
• 🩸 Venous thromboembolism (DVT / PE).
• 💓 Atrial fibrillation (stroke prevention).
• 🧪 Antiphospholipid syndrome.
• Rheumatic mitral stenosis with AF.

🎨 Warfarin Tablet Colours (UK)

• 🟤 Brown – 1 mg
• 🔵 Blue – 3 mg
• 🌸 Pink – 5 mg

🔎 Monitoring: INR

• INR standardises prothrombin time (extrinsic pathway).
• Most indications: Target 2.0–3.0 (aim 2.5).
• Mechanical mitral valve: Target 2.5–3.5.
• Check INR 3–5 days after dose change or interacting drug.

🚑 Reversal of Warfarin

• Minor INR elevation, no bleeding: Omit dose ± oral vitamin K.
• Major bleeding:
  • IV Vitamin K
  • Prothrombin Complex Concentrate (e.g., Beriplex/Octaplex)
• FFP only if PCC unavailable.

⚠️ Drug & Dietary Interactions

• 🍒 Cranberry – ↑ INR (CYP2C9 inhibition).
• 💊 Amiodarone – ↑ INR.
• 💊 Ciprofloxacin, macrolides – ↑ INR.
• 💊 NSAIDs – ↑ bleeding risk (platelet effect).
• 🌿 St John’s Wort – ↓ INR.
• 🌿 Ginkgo – ↑ bleeding risk.
• 🥬 Variable vitamin K intake (leafy greens) → INR instability.
• 🍺 Alcohol (binge ↑ INR; chronic ↓ INR).

📖 Duration of Therapy (General Principles)

• Provoked DVT/PE → 3 months.
• Unprovoked VTE → Consider long-term therapy.
• Mechanical valve → Lifelong.
• APS → Often lifelong.

🔁 Bridging Therapy

• Required when initiating warfarin for acute VTE.
• Continue LMWH for ≥5 days AND until INR ≥2 for ≥24h.
• Perioperative bridging only for high thrombotic risk patients.
• Wait ≥48h post high-bleeding-risk surgery before restarting LMWH.

⚠️ Side Effects

• 🩸 Bleeding (GI, intracranial).
• 🧬 Skin necrosis (early, protein C deficiency).
• 👶 Teratogenic (1st trimester risk – nasal hypoplasia, stippled epiphyses).
• 🦴 Long-term: osteoporosis (rare).

🚫 Contraindications & Cautions

• Pregnancy (except specialist mechanical valve cases).
• Active major bleeding.
• Severe uncontrolled hypertension.
• Recent intracranial haemorrhage.
• Unreliable adherence.

🩺 Practical Prescribing

• Typical initiation: 3–5 mg daily.
• Lower doses in elderly, liver disease, malnourished.
• Ensure anticoagulation booklet issued.
• Educate patient on bleeding signs.
• Check INR 3–5 days after starting interacting drugs.

🧠 Clinical Pearls

• INR rise ≠ full anticoagulation early on.
• Always check for drug interactions before prescribing antibiotics.
• Mechanical valve + DOAC = contraindicated.
• Never stop anticoagulation abruptly in high-risk patient without plan.

📚 Reference

• BCSH Guidelines on Oral Anticoagulation with Warfarin