What is the recommended treatment for urgent reversal of anticoagulation in patients taking Warfarin (coumarin) with major bleeding or requiring emergency surgery, using Prothrombinex (prothrombin complex concentrate)?

Urgent Reversal of Warfarin Anticoagulation Using Prothrombinex (PCC)

For patients taking warfarin with major bleeding or requiring emergency surgery, four-factor prothrombin complex concentrate (Prothrombinex) at a dose of 50 units/kg (maximum 5000 units) plus intravenous vitamin K 10 mg is the recommended treatment for urgent anticoagulation reversal. 1, 2

Indications for Urgent Reversal

• Major bleeding (defined as bleeding with hemodynamic compromise, bleeding in critical anatomic sites, acute drop in hemoglobin >2 g/dL, or requirement of >2 units of blood) 1
• Emergency surgery or invasive procedures with high bleeding risk
• Intracranial hemorrhage (highest priority for immediate reversal)

Dosing Algorithm for Prothrombinex

The dose of Prothrombinex should be based on the patient's weight and INR level:

INR Level	Prothrombinex Dose
2 to <4	25 units/kg (maximum 2500 units)
4 to 6	35 units/kg (maximum 3500 units)
>6	50 units/kg (maximum 5000 units)

2

Administration Protocol

1. Administer Prothrombinex at the appropriate dose based on weight and INR
2. Simultaneously administer vitamin K 10 mg IV to sustain the reversal achieved by PCC 1, 2
3. Check INR 30-60 minutes after PCC administration to confirm adequate reversal 2
4. Target INR <1.5 for emergency surgery or invasive procedures 3
5. Continue monitoring INR every 6 hours until INR <5, then every 12-24 hours until stable 2

Evidence Supporting Prothrombinex Use

Prothrombinex is strongly preferred over fresh frozen plasma (FFP) for urgent warfarin reversal due to:

• More rapid INR correction (mean difference -6.50 hours compared to FFP) 4
• Lower risk of volume overload (OR 0.27,95% CI; 0.13-0.58) 4
• Reduced all-cause mortality compared to FFP (OR= 0.56,95% CI; 0.37-0.84) 4
• No increased risk of thromboembolism compared to FFP (OR 0.91,95% CI; 0.44-1.89) 4

Special Considerations

For Intracranial Hemorrhage

• Immediate reversal is critical to prevent hematoma expansion
• Administer Prothrombinex 50 units/kg plus vitamin K 10 mg IV without waiting for INR results 1

For Emergency Surgery

• Target INR ≤1.5 before proceeding with surgery 3
• Prothrombinex can effectively reverse warfarin within 1 hour to allow for procedures including neuraxial blockade 5

Thrombotic Risk

• The risk of thromboembolism following Prothrombinex administration is approximately 4.6% within 30 days 6
• This risk is primarily related to the underlying condition requiring anticoagulation rather than the PCC itself 6

Resumption of Anticoagulation

• For patients at high risk of thrombosis, anticoagulation should be restarted within 72 hours once hemostasis is achieved 2
• Consider therapeutic doses of unfractionated heparin or low molecular weight heparin during the period of subtherapeutic INR 2
• When resuming warfarin, start at a lower dose than the previous maintenance dose 2

Common Pitfalls to Avoid

1. Delaying reversal while waiting for INR results in life-threatening bleeding
2. Using FFP instead of Prothrombinex when PCC is available (slower reversal, volume overload risk)
3. Omitting vitamin K administration (essential for sustaining the reversal achieved by PCC)
4. Failing to monitor INR after reversal to confirm adequate correction
5. Delaying resumption of anticoagulation in high-risk patients once hemostasis is achieved

Prothrombinex has been shown to be effective when used alone for warfarin reversal, without the need for supplementary FFP 7, contradicting older guidelines that recommended combining PCC with FFP.