Q2i: Important pharmacological considerations when stopping warfarin & commencing prophylactic LMWH in the peri-operative period


  • Competitively inhibits Vit K EPOXIDE REDUCTASE
  • ∴↓[Reduced Vit K] which is essential to activate factors II, VII, IX, X, Protein C/S
  • Used for prophylaxis of systemic embolization (AF, prosthetic valves, prevention DVT/PE)


  • Binds to AntiThrombin III & inhibits Xa > thrombin
  • Prophylactic doses used for DVT/PE prevention post op
  • Using prophylactic cf. therapeutic dose post op ↓risk of bleeding but ↑risk thromboembolic event post op in high risk patients (hypercoagulable states, recurrent DVT/PE)

Stopping Warfarin → Starting Heparin

  • Warfarin stopped 3 – 6 days pre-op
    • Slow clearance 3mL/kg/min
  • Prolonged warfarin action:

↓ Metabolism

Liver dysfunction

↓ Synthetic clotting factors

Liver impairment

Cytokine inhibition (amiodarone, fluconazole)

Vit K deficiency


NB: Check INR day before surgery

  • Initially hypercoagulable due to inhibition of protein C/S (endogenous anticoags)
  • LMWH started D1 post-op OR 2 – 3 days after warfarin ceased
    • Activates Antithrombin III → inhibits Xa & II (but Xa > > II)
    • Predictable & reliable
    • High bioavailability S/C
    • Lower risk of HITS
    • Last dose to be at least 12hr prior CNB
    • Renally excreted ∴↓ dose renal failure


  • Restart warfarin
  • Continue LMWH until INR therapeutic


  • If ↑INR → PTX/FFP
  • Protamine only neutralises 65% of LMWH activity