What is the reversal protocol for Warfarin (Coumadin) anticoagulation?

From the Guidelines

Warfarin reversal should be guided by the clinical scenario and INR level, with vitamin K administration and prothrombin complex concentrate (PCC) being the cornerstone of treatment, as recommended by the 2020 ACC expert consensus decision pathway 1. For non-urgent reversal, simply holding warfarin doses and monitoring INR may be sufficient.

• For mild elevations (INR 4-5), 1-2.5 mg of oral vitamin K is recommended, which can lower the INR within 24 hours 1.
• For more significant bleeding risk (INR 5-9), 2.5-5 mg of oral or intravenous vitamin K is recommended, with the option to administer PCC at 25-50 units/kg if rapid reversal is required 1.
• In cases of life-threatening hemorrhage (INR >9), PCC at 25-50 units/kg should be administered immediately, along with 5-10 mg of IV vitamin K, as this combination provides the most rapid and effective reversal of anticoagulation 1. Key considerations in warfarin reversal include:
• The choice of vitamin K administration route, with oral administration being convenient and safe, but intravenous administration providing a more rapid response 1.
• The use of PCC, which contains purified vitamin K-dependent clotting factors and can be stored at room temperature, making it a convenient option for rapid reversal 1.
• The importance of regular INR monitoring after reversal to ensure appropriate correction and minimize the risk of thromboembolic events 1.

From the FDA Drug Label

OVERDOSAGE ... 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. ... If minor bleeding progresses to major bleeding, give 5 to 25 mg (rarely up to 50 mg) 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 reversal protocol for Warfarin (Coumadin) anticoagulation involves:
  • Discontinuing warfarin sodium tablets therapy
  • Administering oral or parenteral vitamin K1
  • In cases of major bleeding, giving 5 to 25 mg (rarely up to 50 mg) parenteral vitamin K1
  • In emergency situations of severe hemorrhage, administering 200 to 500 mL of fresh whole blood or fresh frozen plasma, or giving commercial Factor IX complex 2

From the Research

Reversal Protocol for Warfarin Anticoagulation

The reversal protocol for warfarin anticoagulation involves several strategies, including the use of vitamin K, prothrombin complex concentrate (PCC), and fresh frozen plasma (FFP) 3, 4, 5, 6.

• For patients with an elevated international normalized ratio (INR) and mild or no bleeding, withholding warfarin and rechecking INR in 1 to 2 days is recommended, with oral vitamin K supplementation added if INR >5 6.
• In cases of major bleeding and elevated INR, hospital admission, vitamin K, fresh frozen plasma, and frequent monitoring are necessary 6.
• Emergent situations require hospitalization, clotting factor replacement, and vitamin K administered by slow intravenous infusion 6.

Comparison of Reversal Agents

Studies have compared the efficacy of different reversal agents, including PCC and FFP 4, 5.

• PCC use was associated with a significant reduction in all-cause mortality compared to FFP, as well as more rapid INR reduction and less volume overload 4.
• Low-dose recombinant Factor VIIa (rFVIIa) was also found to be effective in reversing warfarin anticoagulation, with a higher proportion of patients achieving an INR of 1.5 or less compared to PCC 5.

Vitamin K Dosing

The dosing of vitamin K for warfarin reversal is an important consideration, with current algorithms not taking into account individual variability in response 7.

• Factors such as patient age, body weight, co-morbidity, frailty, warfarin daily dose, and genetic polymorphisms can affect response to vitamin K and thus the rate and extent of INR reversal 7.
• A more individualized approach to vitamin K dosing may be necessary to improve the safety of warfarin therapy 7.