Warfarin Associated Coagulopathy: Reversal Options and Practical Considerations for the Pharmacist

Edith A. Nutescu, PharmD, MS, FCCP
Clinical Professor, Department of Pharmacy Practice
University of Illinois, College of Pharmacy
Co-Director, Center for Pharmacoepidemiology & Pharmacoeconomic Research
Co-Director, Personalized Medicine Service
University of Illinois Hospital & Health Sciences System
Chicago, Illinois

Clinical Considerations for Reversing Warfarin-Induced Coagulopathy

The management of patients receiving oral anticoagulants, who are bleeding or need an urgent invasive procedure, requires weighing the risks for thrombosis and bleeding with the consideration of short- and long-term treatment goals. Individualization of therapy is necessary, taking into consideration these goals, along with the patient's age, renal function, clinical status, and laboratory test results. Guidelines developed by the American College of Chest Physicians (ACCP) recommend withholding warfarin and, because of the lag time needed for depletion of vitamin K-dependent clotting factors, the administration of vitamin K and clotting factor concentrates when urgent warfarin reversal is needed.

In warfarin-treated patients with bleeding, vitamin K 5 to 10 mg by slow intravascular injection in addition to PCC-4 is recommended for urgent warfarin reversal.When the INR is > 10, pharmacologic intervention to reverse anticoagulation from warfarin is indicated.
Reversal is not warranted when the INR is ≤ 10 unless the patient is bleeding or requires urgent surgery. Reversal is indicated for patients treated with warfarin who are bleeding or require urgent surgery regardless of the INR. For patients treated with warfarin, who require surgery within 24 hours, a 2-drug combination of vitamin K 5 to 10 mg slow intravascular injection plus (1) PCC-4, (2) rFVIIa, or (3) aPCC will likely be effective for lowering the INR based on the published literature.

If surgery is needed, but can be delayed for more than 24 hours, intravascular vitamin K alone may suffice for warfarin reversal based on the pharmacodynamics of vitamin K. When urgent reversal is necessary, the ACCP guidelines recommend PCC-4 before FFP. These recommendations were based on several key differences between PCC-4 and FFP, including a more rapid INR reversaln (i.e., using FFP may delay treatment up to 1 hour because it requires the patient's blood to be typed and screened), it must be thawed before use, and it is infused at a slower rate. In addition, there is a higher potential for adverse sequelae related to fluid overload with FFP. The maximum volume of PCC-4 administered is approximately 250 mL, while more than a liter of FFP may be necessary for the same INR reversal. FFP also has an increased risk for transfusion-related adverse events, including acute lung injury, disease transmission, and hypersensitivity reactions. 

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