How to manage coagulopathy in a patient on Eliquis (apixaban) with an elevated International Normalized Ratio (INR)?

From the Guidelines

Managing coagulopathy in a patient on Eliquis (apixaban) with an elevated INR requires immediate discontinuation of apixaban and consideration of reversal agents, with Andexanet alfa being the preferred choice for life-threatening bleeding. The dosing of Andexanet alfa depends on the apixaban dose and timing of last dose: for patients on ≤5 mg or if taken >8 hours ago, give 400 mg IV bolus followed by 4 mg/min infusion for 120 minutes; for higher doses or recent administration, give 800 mg IV bolus followed by 8 mg/min infusion for 120 minutes 1. If Andexanet alfa is unavailable, prothrombin complex concentrate (PCC) at 25-50 units/kg can be used. For non-life-threatening bleeding, supportive care with fluid resuscitation, local hemostatic measures, and transfusion of blood products as needed may be sufficient. It's essential to investigate and treat the underlying cause of the elevated INR, which may be due to liver dysfunction or vitamin K deficiency, as apixaban typically does not significantly alter INR 1.

Some key points to consider:

• Andexanet alfa is the specific reversal agent for factor Xa inhibitors like apixaban, and its use is recommended for life-threatening bleeding 1.
• PCC can be used as an alternative to Andexanet alfa, but its effectiveness may vary depending on the specific product and patient factors 1.
• The management of coagulopathy in patients on apixaban requires a multidisciplinary approach, including discontinuation of the anticoagulant, administration of reversal agents, and supportive care.
• The underlying cause of the elevated INR should be investigated and treated concurrently, as it may be due to an underlying condition such as liver dysfunction or vitamin K deficiency 1.

In terms of specific dosing and administration, the guidelines recommend the following:

• Andexanet alfa: 400 mg IV bolus followed by 4 mg/min infusion for 120 minutes for patients on ≤5 mg or if taken >8 hours ago; 800 mg IV bolus followed by 8 mg/min infusion for 120 minutes for higher doses or recent administration 1.
• PCC: 25-50 units/kg, depending on the specific product and patient factors 1.

Overall, the management of coagulopathy in patients on apixaban with an elevated INR requires a careful and individualized approach, taking into account the patient's specific clinical circumstances and the availability of reversal agents.

From the FDA Drug Label

Apixaban affects INR, so that initial INR measurements during the transition to warfarin may not be useful for determining the appropriate dose of warfarin Switching from warfarin to apixaban: Warfarin should be discontinued and apixaban started when the international normalized ratio (INR) is below 2. 0.

The management of coagulopathy in a patient on Eliquis (apixaban) with an elevated International Normalized Ratio (INR) is not directly addressed in the provided drug label. However, it is mentioned that apixaban affects INR measurements, making them potentially unreliable during transitions between anticoagulants.

• When switching from warfarin to apixaban, the recommendation is to start apixaban when the INR is below 2.0.
• There is no specific guidance on managing elevated INR in patients already on apixaban. Given the lack of direct information on managing coagulopathy with elevated INR in patients on apixaban, a conservative approach would be to consult the prescribing information for warfarin or other anticoagulants, or seek guidance from a clinical expert, as the provided label does not offer a clear strategy for this scenario 2.

From the Research

Managing Coagulopathy in Patients on Eliquis (Apixaban) with Elevated INR

To manage coagulopathy in a patient on Eliquis (apixaban) with an elevated International Normalized Ratio (INR), several strategies can be considered:

• Assessing the risk of bleeding: The risk of hemorrhage approximately doubles for each one point increase in the INR above 3.0 3.
• Withholding anticoagulant therapy: Reducing a prolonged INR to within the desired therapeutic range requires that oral anticoagulants be withheld 3.
• Vitamin K administration: Vitamin K may be administered to reduce the INR, with oral administration being the preferred route due to the risk of anaphylactoid reactions with intravenous administration 4.
• Prothrombin complex concentrates (PCC) or fresh frozen plasma (FFP) transfusion: For urgent reversal of anticoagulation, PCC or FFP may be used, with PCC being associated with a significant reduction in all-cause mortality and more rapid INR reduction compared to FFP 5.

Considerations for Reversal of Anticoagulation

When considering reversal of anticoagulation, the following points should be taken into account:

• Efficacy of FFP: FFP may not be effective in achieving haemostatically effective levels of factor IX, and clotting factor concentrates may be a more effective option for complete and immediate correction of the coagulation defect 6.
• Risk of thromboembolism: The risk of thromboembolism associated with overcorrection of the INR appears to be in the same range as the risk of bleeding due to over-anticoagulation 4.
• Patient characteristics: Patient characteristics, such as advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding 4.

Monitoring and Adjustment

Regular monitoring of the INR and adjustment of the anticoagulant therapy as needed is crucial to prevent over-anticoagulation and minimize the risk of bleeding:

• INR monitoring: Regular INR monitoring is essential to assess the effectiveness of anticoagulant therapy and adjust the dose as needed 3.
• Dose adjustment: The dose of anticoagulant therapy should be adjusted based on the INR results to maintain a therapeutic INR range and minimize the risk of bleeding 3.