warfarin

The Vitamin K Antagonist

Historic gold-standard oral anticoagulant. Despite DOAC dominance, it remains the mandatory agent for specific high-risk indications.

• Mechanism: Inhibits Vitamin K Epoxide Reductase (VKORC1) $\to$ depletes Factors II, VII, IX, X, Protein C/S.
• Dosing: Highly variable. Target INR usually 2.0–3.0.
• PK: Onset 48-72h. Full effect 5-7 days (requires bridging). Half-life: 40h.

indications (“be calm”)

DOACs are contra-indicated or inferior in these settings:

• Breastfeeding (DOACs unsafe/unknown; Warfarin safe).
• CKD Stage 4/5 (Creatinine Clearance $<15-30$ mL/min).
• Antiphospholipid Syndrome (Triple Positive or Arterial thrombosis).
• LV Thrombus (Classic choice, though DOAC data emerging).
• Mechanical Heart Valves (Absolute indication; DOACs = Death).

management & monitoring

• Starting: 5 mg PO daily (2 mg if frail/elderly).
• Bridging: Must bridge with LMWH/UFH for minimum 5 days AND until INR $\ge 2.0$ for 24h.
• Interactions: Antibiotics (Septra/Flagyl $\uparrow$ INR), Amiodarone ($uparrow$ INR), leafy greens (Vit K $downarrow$ INR).

reversal (emergency)

major bleed

4-Factor PCC (Octaplex/Beriplex) is superior to FFP.

Clinical State	INR	Action
Bleeding (Life Threatening)	Any	PCC (2000-3000 U) + Vit K 10 mg IV (slow).
Bleeding (Non-Major)	Any	Hold Warfarin + Vit K 2.5–5 mg PO.
No Bleeding	4.5 – 9.0	Hold Warfarin $\pm$ Vit K 1–2.5 mg PO.
No Bleeding	> 9.0	Hold Warfarin + Vit K 2.5–5 mg PO.

cautions

• Pregnancy: Teratogenic (fetal warfarin syndrome). Contraindicated (except mechanical valves 2nd trimester).
• Skin Necrosis: Rare paradox in first few days (Protein C depletion).

related pages: Deep Vein Thrombosis, Anticoagulant Reversal, Antiphospholipid Syndrome