From the Guidelines
Warfarin can be rapidly reversed using a combination of 4-factor prothrombin complex concentrate (PCC) and low-dose vitamin K (<5 mg) for urgent reversal of anticoagulation in life-threatening bleeding situations. This approach is based on the most recent and highest quality evidence available, including a study published in 2020 in the Journal of the American College of Cardiology 1. The use of 4-factor PCC is preferred due to its faster onset of action, minimal risk of fluid overload, and lower risk of transmitting infection compared to fresh frozen plasma (FFP) 2.
Key Considerations for Reversal
- 4-factor PCC contains factors II, VII, IX, and X, and is dosed based on INR and body weight, with typical doses ranging from 25-50 units/kg intravenously 1.
- Vitamin K should be administered concurrently with PCC at a low dose (<5 mg) to reduce the risk of hypercoagulopathy, especially in patients who require early re-anticoagulation 2.
- FFP can be used if PCC is unavailable, but it requires larger volumes and more time to administer, and carries a higher risk of fluid overload and transmitting infection 2, 1.
- Recombinant factor VIIa may be considered in extreme cases, but it carries thrombotic risks and is not a first-line treatment for warfarin reversal 1.
Monitoring and Follow-up
- INR should be monitored frequently after reversal to ensure adequate correction and guide additional dosing if needed 2, 1.
- The goal of reversal is to achieve an INR that is safe for the patient's underlying condition, while minimizing the risk of thromboembolic events 1.
Evidence-Based Recommendations
The recommendation for using 4-factor PCC and low-dose vitamin K for warfarin reversal is based on the highest quality evidence available, including studies published in reputable journals such as Gut 2 and the Journal of the American College of Cardiology 1. These studies demonstrate the efficacy and safety of this approach for rapid reversal of warfarin in life-threatening bleeding situations.
From the FDA Drug Label
BALFAXAR (prothrombin complex concentrate, human-lans) is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with need for an urgent surgery/invasive procedure. Excessive anticoagulation, with or without bleeding, may be controlled by discontinuing warfarin sodium tablets therapy and if necessary, by administration of oral or parenteral vitamin K1. In emergency situations of severe hemorrhage, clotting factors can be returned to normal by administering 200 to 500 mL of fresh whole blood or fresh frozen plasma, or by giving commercial Factor IX complex
The method for rapid reversal of warfarin includes:
- Administration of prothrombin complex concentrate (IV), such as BALFAXAR 3
- Administration of oral or parenteral vitamin K1 4
- Administration of fresh whole blood or fresh frozen plasma 4
- Administration of commercial Factor IX complex 4
Key points:
- Discontinuation of warfarin therapy is also necessary
- These methods are used to control excessive anticoagulation and bleeding
- The choice of method depends on the severity of the situation and the patient's condition 4
From the Research
Rapid Reversal of Warfarin
The method for rapid reversal of warfarin (coumarin anticoagulant) involves the use of prothrombin complex concentrates (PCC) and fresh frozen plasma (FFP) in combination with vitamin K(1) 5, 6, 7, 8.
- PCC is preferred over FFP for immediate reversal due to its faster and more predictable effect 5, 8.
- Vitamin K(1) is essential for sustaining the reversal achieved by PCC or FFP 5, 8.
- The choice of intervention depends on the International Normalized Ratio (INR), presence of bleeding, and need for and timing of surgery 7, 8.
Prothrombin Complex Concentrates
- Prothrombinex-HT is the only PCC approved in Australia and New Zealand for warfarin reversal, containing factors II, IX, and X, and low levels of factor VII 5.
- Prothrombinex-VF is another PCC used for warfarin reversal in Australia and New Zealand, containing factors II, IX, X, and low levels of factor VII 8.
- Three-factor PCC and four-factor PCC are also available, with the latter containing factor VII in an inactivated form 7.
Fresh Frozen Plasma
- FFP can be used when PCC is unavailable, but it is not routinely needed in combination with PCC 5, 8.
- FFP should be added to PCC as a source of factor VII when used for warfarin reversal 5.
Vitamin K(1)
- Vitamin K(1) can be given orally or intravenously to reverse the anticoagulant effect of warfarin 5, 8.
- The injectable formulation of vitamin K(1) is preferred for oral use due to its flexible dosing 5.