Warfarin

Background

• Blocks activation of vit K thereby interfering w/ activation of factors II, VII, IX, X
  • Also blocks synthesis of antithrombotic proteins C and S
    • Causes transient (24-36hr) prothrombotic effect at the start of therapy
    • Bridge with heparin until INR is in desired range for 2d
• Albumin bound; metabolized by liver
• Contraindicated in pregnancy

Dosing

1. Day 1: 5-7.5 mg po QHS (to ensure absorption on an empty stomach)
   1. 2.5-7.5 mg thereafter (most often 5 mg)
2. Increase in INR of >0.3-0.4 units per day necessitates dose reduction
3. CHF, liver disease, Vitamin K def, drugs may influence warfarin response

Range (INR)

1. 2.5-3.5: Mechanical prosthetic valves or recurrent thromboembolism
2. 2.0-3.0: All other indications

Complications

1. Bleeding
   1. Risk is increased when INR is in 3-4.5 range
   2. Exponential increase occurs when INR is >5
   3. Avoid giving pts NSAIDs, sulfas, macrolidies (azithromycin ok), fluoroquinolones
2. Skin necrosis
   1. Primarily occurs in pts w/ protein C deficiency
   2. Occurs 3-8d after starting treatment
   3. Treatment
      1. Discontinue warfarin; start parenteral anticoagulant
      2. Vitamin K1 administration

Reversal

• See Warfarin (Coumadin) Reversal

Source

Tintinalli