FAQs
Should Fresh Frozen Plasma Be Used to Reverse the Effects of Warfarin?
The Answer: "Yes, Sometimes"
The patient who is over-anticoagulated with warfarin (whether bleeding or not) can present a significant challenge. As you probably know, warfarin acts by inhibiting the gamma carboxylation of factors II, VII, IX, and X (the vitamin K dependent factors) in the liver. In order to reverse the anticoagulation, either the blockage to production must be removed or sufficient quantities of the actual factors must be supplied. In some cases, a prompt response may include the use of FFP (or a similar plasma product known as "FP24"), but in many cases, it likely will not. The best strategy depends on whether or not the patient is bleeding. The following is summarized from the excellent recommendations made in 2008 in the journal Chest (see Chest 133:160S-198S).
The first step (in patients who are not actively bleeding), in the correction of warfarin over-anticoagulation is simple: Hold the next dose of warfarin! In patients who are mildly anticoagulated (INR <5.0), this intervention alone is often enough to get the patient back to a more acceptable range.
If the INR is more significantly elevated (>5.0), however, the mainstay of therapy (in addition to holding the next warfarin dose) is vitamin K, which overcomes the drug-induced blockage and allows the factors listed above to be produced in normal forms. Vitamin K is typically administered orally in this situation, and it works great! Please note that in these recommendations, FFP is NOT indicated, no matter how high the INR, if the patient is not bleeding!
This leads me to one of my all-time favorite quotes about warfarin, that I heard so long ago that I can't remember who actually said it! At any rate, here it is: "Warfarin alone does not cause bleeding. The exception is if it is shot out of a cannon at the patient!" Beautiful!
In a bleeding patient that is over-anticoagulated, the intervention, by design, becomes more aggressive. In addition to holding the next warfarin dose (obviously), the vitamin K should be administered intravenously. There are some clinicians that don't like that idea due to cases of anaphylaxis that have been reported, but IV vitamin K is used successfully all the time. Obviously, absorption is not an issue when an intravenous dose is given, but it still takes awhile for the liver to replenish the depleted vitamin K-dependent factors sufficiently to make a difference. Most of the time, IV vitamin K takes about 6 hours to work.
However, the recommendations also allow for the use of blood products to immediately correct the factor levels, if necessary. FFP is a good choice in this situation, at standard doses of 10-20 ml/Kg (note that in most patients, this will be FAR more than the typical two units that are requested by most clinicians). You should also note, however, that infusion of prothrombin complex concentrate (PCC) may be an even better option than FFP in this situation, as PCC contains the specific factors needed to correct the anticoagulation, and nothing else.
Unfortunately, however, most patients in the U.S. still don't get away without receiving FFP in this situation. Neither of the forms of PCC approved by the FDA has substantial quantities of factor VII, so in general, these patients will need a small amount of transfused plasma (usually no more than a couple of units).
People still get nervous about PCC because many remember the reports of increased thrombosis that occurred with the activated form of PCC, but most consider the current preparations of PCC safe (the modern methods of preparing the product minimize activation of the coagulation factors). Recombinant activated factor VII concentrate (better known by most as "NovoSeven") is also recommended for consideration in this circumstance.
So, the bottom line is this: It is reasonable to consider FFP transfusion for reversal of warfarin effect in bleeding patients, potentially as part of a combination of therapeutic interventions that may include factor concentrates, vitamin K, and holding the patient's warfarin dose. For purely prophylactic situations, however, FFP is generally not indicated.