Warfarin

• MOA
  • Inhibits vitamin K epoxide reductase complex 1 (VKORC1)
  • Vitamin K antagonist - affects factors 2, 7, 9 and 10
  • Extrinsic (trauma/tissue factor) and intrinsic (damaged surface) pathways both affected
  • Starting warfarin initially causes ≈ 5/7 increased thrombotic tendency because
    • An initial effect of warfarin is to ↓Protein C & S → ↑ Thrombosis
    • Factor 7 ↓s first this → ↑s INR but other coagulations factors may still be high (INR falsely reassuring initially, after starting warfarin)
  • Not safe in pregnancy → ↑ Birth defects
  • Half-life 40 hours, duration of effect = 2-5 days
  • Current Australasian guidelines: Start on 5mg
  • Interactions: Amiodarone, Antibiotics, Statins, Anticonvulsants
  • INR > 6 – need to be worried
• Monitor
  • INR
• Surgery
  • Stop 5 days before elective or reverse effect with vitamin K (24 hrs), FFP and prothrombinex
• Dose
  • Guided by INR
  • Takes 3 days reflect change in dose in INR
• Considerations
  • Risk of effective dose reduction or increase due to impact on CYP enzymes
  • Bleeding risk
  • Easily reversible with Vitamin K, FFP and prothrombinex
• Perioperative management
  • Withhold for 5 days
  • If high risk VTE - bridging clexane to start 3 days pre procedure
  • Can check INR 1-2 days before procedure
• Reversing
  • Expect rebound hypercoagulability
  • Can operate once INR < 1.6
  • Consider to cover with clexane/ heparin if
    • For high & moderate risk
  • Reversal approach
    • Rapid reversal e.g bleeding or emergency surgery
      • 10mg Vitamin K
      • Prothrombinex + FFP
    • Supra-therapeutic INR
      • Oral vitamin K
      • W/H Warfarin
      • Monitor INR
• Prothrombinex – usually 30-50 U/kg
  • Purified human coagulation factors from plasma
  • Has II, IX, X
  • Don’t need to match ABO
  • Half-life 3-60 hours – what little 7 there is gets used up first
• FFP
  • To supplement for the lack of VII in the above
  • 150-300mL
  • Do need to match ABO
• Vitamin K - Orally, if possible, as IV has been linked to anaphylaxis
  • 2mg if just need to reduce as the level has crept up
  • 5-10mg if need reversal
  • Acts within 6-12 hours
• Need to give if want to sustain effect of FFP, Prothrombinex
• Restart 12-24 hours post-operative