Recommended Dosing for Kcentra (Prothrombin Complex Concentrate) for Urgent Warfarin Reversal
For urgent reversal of warfarin anticoagulation, Kcentra (4-factor PCC) should be dosed based on the patient's pretreatment INR level: 25 units/kg for INR 2-<4,35 units/kg for INR 4-6, and 50 units/kg for INR >6, with maximum doses of 2500,3500, and 5000 units respectively. 1
Dosing Algorithm for Kcentra Administration
The 2023 ACC/AHA/ACCP/HRS guidelines provide specific dosing recommendations for 4-factor PCC (Kcentra) based on the patient's pretreatment INR:
- For INR 2 to <4: 25 units/kg (maximum 2500 units)
- For INR 4 to 6: 35 units/kg (maximum 3500 units)
- For INR >6: 50 units/kg (maximum 5000 units)
Administration Guidelines
- Administer intravenous vitamin K 10 mg over 10-20 minutes in addition to 4-factor PCC 1, 2
- Onset of action is within 10 minutes with effects lasting approximately 8 hours 1
- Repeat INR within 30 minutes after administration to assess efficacy 1
- Continue monitoring every 6-8 hours for 24-48 hours 2
Clinical Scenarios Requiring Urgent Reversal
Urgent reversal with Kcentra is indicated in the following situations:
- Life-threatening or uncontrolled bleeding in patients on warfarin
- Need for emergency surgery or urgent invasive procedures
- Intracranial hemorrhage with INR ≥1.4 2
- Major non-intracranial bleeding with INR ≥4.5 2
Advantages Over Alternative Reversal Strategies
Kcentra (4-factor PCC) offers several advantages over fresh frozen plasma (FFP):
- More rapid INR correction (within 10 minutes vs. hours for FFP) 1, 3
- Avoidance of volume overload 3
- More complete correction of coagulopathy 3
- No need for blood type matching or thawing
Important Considerations and Precautions
- 4-factor PCC is preferred over 3-factor PCC when available 2
- PCC alone is preferred over combination with FFP or rFVIIa for initial reversal 2
- May not be indicated for patients with thromboembolic events in the previous 3 months 1
- Monitor for potential thrombotic complications, which have been reported in some studies 3, 4
- If repeat INR remains ≥1.4 within 24-48 hours after initial PCC, consider additional FFP 2
Special Populations
- For patients with mechanical heart valves, avoid high-dose vitamin K as it may create a hypercoagulable condition; lower doses (1 mg) should be used if necessary 2
- Elderly patients (≥65 years) may require closer monitoring due to increased bleeding risk 2
The evidence consistently supports weight-based dosing of Kcentra according to pretreatment INR levels, with concurrent administration of vitamin K for sustained reversal of warfarin's anticoagulant effects.