From the Guidelines
Fresh frozen plasma (FFP) and vitamin K are not recommended as first-line treatments for reversing warfarin-associated active bleeding due to their limitations in providing rapid and effective reversal. For active bleeding on warfarin, prothrombin complex concentrate (PCC) is the preferred agent because it rapidly restores clotting factors within minutes, whereas FFP takes hours to work and requires large volumes (10-15 mL/kg), potentially causing fluid overload in patients with cardiac or renal issues. FFP also requires thawing and blood type matching, delaying critical treatment. While vitamin K is important for sustaining reversal by promoting new clotting factor synthesis, it works too slowly (taking 4-24 hours) to address immediate bleeding. Additionally, FFP carries risks of transfusion reactions, transfusion-associated circulatory overload, and infectious disease transmission. Some key points to consider when using PCC for warfarin reversal include:
- PCC is available in 3-factor and 4-factor formulations, with 4-factor PCC being preferred due to its more rapid and complete factor replacement 1.
- The dose of PCC is based on the patient's weight and INR level, with a recommended dose of 25-50 units/kg 1.
- Vitamin K should be administered concomitantly with PCC to stimulate production of vitamin K-dependent coagulation factors 1.
- The use of PCC is associated with a lower risk of thromboembolic events compared to FFP 1.
- PCC has a faster onset of action and minimal risk of fluid overload and transmitting infection compared to FFP 1. For active bleeding on warfarin, the recommended approach is PCC administration (25-50 units/kg based on INR) combined with vitamin K (5-10 mg IV) for sustained reversal, followed by addressing the underlying cause of bleeding and reassessing anticoagulation needs once bleeding is controlled 1.
From the FDA Drug Label
OVERDOSAGE ... 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 A risk of hepatitis and other viral diseases is associated with the use of these blood products; Factor IX complex is also associated with an increased risk of thrombosis. Therefore, these preparations should be used only in exceptional or life-threatening bleeding episodes secondary to warfarin sodium overdosage
The use of FFP (Fresh Frozen Plasma) and vitamin K is not recommended for reversal of warfarin active bleeding except in exceptional or life-threatening bleeding episodes due to the associated risks, including:
- Hepatitis and other viral diseases with FFP
- Thrombosis with Factor IX complex These preparations should be used with caution and only when necessary, as they can also precipitate pulmonary edema in elderly patients or patients with heart disease 2.
From the Research
Reasons for Not Recommending FFP and Vitamin K
- FFP and vitamin K are not recommended for the reversal of warfarin in active bleeding due to several reasons:
- Slower reversal of international normalized ratio (INR) compared to prothrombin complex concentrates (PCC) 3, 4, 5
- Higher risk of volume overload with FFP compared to PCC 3, 5
- Less effective in achieving haemostasis compared to PCC 3, 4
- Longer time to INR correction with FFP and vitamin K compared to PCC 3, 4, 5
Comparison with Prothrombin Complex Concentrates
- PCC has been shown to be more effective in reversing warfarin anticoagulation compared to FFP and vitamin K 3, 4, 6, 5
- PCC is associated with a lower risk of thromboembolic events compared to FFP and vitamin K 3, 4
- PCC allows for a more rapid reversal of coagulopathy, which is vital in limiting the extent of intracranial hemorrhage (ICH) 5
Specific Patient Populations
- In geriatric trauma patients, PCC has been shown to accelerate INR reversal and diminish the extension of ICH compared to FFP and vitamin K 5
- In patients with traumatic intracranial hemorrhage, PCC has been shown to be more effective in reversing warfarin anticoagulation compared to FFP and vitamin K 4