What is the recommended dose and administration of Prothrombin Complex Concentrate (PCC) and vitamin K for urgent reversal of warfarin (coumarin) anticoagulation?

Urgent Warfarin Reversal Protocol

For urgent reversal of warfarin anticoagulation in patients with life-threatening bleeding or requiring emergency surgery, administer four-factor prothrombin complex concentrate (4F-PCC) at a dose of 25-50 IU/kg based on INR level, along with intravenous vitamin K 10 mg. 1

PCC Dosing Algorithm

The recommended dosing strategy for 4F-PCC is:

• INR 2.0-4.0: 25 IU/kg
• INR 4.0-6.0: 35 IU/kg
• INR >6.0: 50 IU/kg 1, 2

Administration Protocol

1. PCC Administration:

   • Administer 4F-PCC intravenously at the calculated dose
   • Infuse slowly according to manufacturer's instructions
   • Expected INR correction occurs within 10-30 minutes 1

2. Vitamin K Administration:

   • Administer 10 mg vitamin K intravenously concurrently with PCC 1
   • Vitamin K should be infused slowly over 20 minutes to minimize risk of anaphylactoid reactions (3 per 100,000 doses) 1
   • This ensures durable reversal as PCC effects are temporary (factor VII half-life is only 6 hours) 1

3. Monitoring:

   • Check INR 30 minutes after PCC administration to confirm adequate reversal 1
   • Target INR ≤1.5 1
   • If INR remains ≥1.4 within 24-48 hours, consider redosing vitamin K 10 mg IV 1
   • Monitor INR regularly over the following week 1

Clinical Considerations

• Preferred Agent: 4F-PCC is strongly preferred over 3F-PCC or fresh frozen plasma (FFP) due to more complete and rapid reversal 1

• FFP Alternative: If PCC is unavailable, administer FFP 10-15 mL/kg IV with vitamin K 10 mg IV 1, 3

• Thrombotic Risk: PCCs carry risk of thrombotic complications. Initiate thromboprophylaxis as soon as bleeding is controlled 1, 4

• Contraindications/Cautions:

  • Consider risks vs. benefits in patients with recent thrombosis, ischemia, heparin-induced thrombocytopenia, or DIC 1
  • Avoid PCC in suspected cerebral venous thrombosis 1

• Vitamin K Considerations:

  • Vitamin K alone is insufficient for urgent reversal (takes 4-24 hours to work) 2
  • Excessive vitamin K (>10 mg) may prevent re-warfarinization for days 1, 2

Special Situations

• Intracranial Hemorrhage: Immediate reversal is critical. Administer PCC and vitamin K without delay to prevent hematoma expansion 1

• Non-Life-Threatening Bleeding: For minor bleeding with elevated INR, consider vitamin K alone (5-10 mg IV) without PCC 3

• Fixed-Dose Alternative: Some centers use fixed-dose PCC (2000 units) regardless of weight or INR, which may be equally effective in achieving target INR ≤1.4 in intracranial hemorrhage 5

By following this protocol, rapid and effective reversal of warfarin anticoagulation can be achieved to minimize morbidity and mortality in emergency situations.