From the Guidelines
For a patient with PT/INR of 21.4/1.81, immediate action is needed to address this severely elevated INR, and the first step is to hold any anticoagulant medications like warfarin and administer 10 mg of oral vitamin K or 10 mg IV vitamin K along with prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP) if the patient is at high risk of bleeding or has active bleeding. The patient's INR is significantly elevated, which increases the risk of bleeding, as seen in the study by the American Heart Association/American College of Cardiology Foundation 1. Key considerations for managing this patient include:
- Stopping warfarin immediately to prevent further elevation of the INR
- Administering vitamin K to promote clotting factor synthesis in the liver and reduce the INR
- Monitoring the patient closely for signs of bleeding and adjusting the treatment plan as needed
- Investigating the cause of the elevated INR, which could include medication interactions, liver disease, dietary changes, or dosing errors, as suggested by the American College of Chest Physicians recommendations 1. The American Heart Association/American College of Cardiology Foundation guide to warfarin therapy 1 recommends that for INR values above 9, vitamin K1, 3 to 5 mg, should be given orally, anticipating that the INR will fall within 24 to 48 hours, and the INR should be monitored closely and vitamin K repeated as necessary. In cases of life-threatening bleeding or serious warfarin overdose, prothrombin complex concentrate replacement therapy is indicated, supplemented with 10 mg of vitamin K1 by slow intravenous infusion; this can be repeated, according to the INR 1. Rechecking the INR in 6-12 hours after intervention and adjusting the treatment plan accordingly is crucial to ensure the patient's safety and prevent further complications.
From the FDA Drug Label
OVERDOSAGE Signs and Symptoms Suspected or overt abnormal bleeding (e.g., appearance of blood in stools or urine, hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from superficial injuries) are early manifestations of anticoagulation beyond a safe and satisfactory level Treatment 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.
The patient's PT/INR is 21.4/1.81, indicating excessive anticoagulation.
- Discontinue warfarin sodium tablets therapy.
- Administer oral or parenteral vitamin K1 if necessary.
- Monitor the patient for signs of bleeding and be prepared to administer clotting factors or blood products if severe hemorrhage occurs. 2
From the Research
Patient with Elevated PT/INR
The patient's PT/INR is 21.4/1.81, indicating an elevated international normalized ratio (INR) which suggests over-anticoagulation.
- The goal of treatment is to urgently reverse warfarin anticoagulation and restore normal hemostasis.
Treatment Options
There are two main treatment options for warfarin reversal:
- Fresh frozen plasma (FFP)
- Prothrombin complex concentrates (PCCs)
Prothrombin Complex Concentrates (PCCs)
PCCs offer a rapid and specific method for replacing vitamin K-dependent clotting factors and restoring normal hemostasis 3, 4, 5.
- PCCs have been shown to be more effective than FFP in shortening the time to INR correction and achieving normalization of INR 4, 5, 6.
- PCCs are also associated with a lower risk of thrombotic adverse events and post-transfusion volume overload compared to FFP 4, 5, 6.
Fresh Frozen Plasma (FFP)
FFP is considered the standard of care for warfarin reversal in some settings, but it has several limitations, including delays in correction, volume overload, and often inadequate correction 3, 5, 7.
- FFP is less effective than PCCs in restoring thrombin generation and factor II levels, and it may not be as effective in achieving rapid INR correction 7.
Recommendation
Based on the available evidence, the use of PCCs is recommended for warfarin reversal in patients with elevated INR, such as the patient in question 4, 5, 6.