Warfarin

Background

• Blocks activation of vitamin K dependent prothrombotic factors II, VII, IX, X
• Blocks synthesis of vitamin K dependent antithrombotic proteins C and S
• Because of differing factor half-lives, can cause transient (24-36 hour) prothrombosis at start of therapy
  • Bridge with heparin for 1-2 days until INR is in desired range
• Albumin bound
• Metabolized by liver
• Contraindicated in pregnancy

Dosing

1. Day 1: 5 - 7.5 mg oral at bedtime (to ensure absorption on empty stomach)
2. Day 2 and beyond: 2.5 - 7.5 mg daily (usually 5 mg)
3. INR increase of >0.3 - 0.4 per day requires dose reduction
4. Response also influenced by congestive heart failure, liver disease, Vitamin K deficiency, many drugs

Target Range of 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 increased when INR >3
   2. Exponential increase when INR >5
   3. Avoid giving NSAIDs, sulfas, macrolidies (azithromycin ok), fluoroquinolones
2. Skin necrosis
   1. Usually in patient with protein C deficiency
   2. Occurs 3 - 8 days after starting treatment
   3. Treatment: stop warfarin, start parenteral anticoagulant, give Vitamin K1 (See Warfarin (Coumadin) Reversal)

Reversal

• See Warfarin (Coumadin) Reversal

See Also

• Coagulopathy (Main)

Source

Tintinalli