From the Guidelines
Eliquis (apixaban) can affect a patient's INR if bleeding occurs, but INR is not the appropriate test to monitor Eliquis therapy, and instead, anti-Factor Xa assays should be used to assess the drug's effect. Eliquis is a direct oral anticoagulant (DOAC) that works by directly inhibiting Factor Xa in the coagulation cascade, unlike warfarin which is monitored using INR 1. If a patient on Eliquis experiences bleeding, healthcare providers should immediately assess the severity of bleeding and consider discontinuing the medication temporarily. For severe bleeding, reversal agents like andexanet alfa (Andexxa) may be administered, with dosing guidance provided in the 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants 1.
Key Considerations
- Laboratory tests that better reflect Eliquis activity include anti-Factor Xa assays, not INR.
- Patients should be advised to seek immediate medical attention for any signs of bleeding such as unusual bruising, nosebleeds, blood in urine or stool, or severe headaches.
- Regular monitoring of complete blood count and renal function is recommended for patients on Eliquis to assess bleeding risk, especially in elderly patients or those with renal impairment.
- The 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM guideline for perioperative cardiovascular management for noncardiac surgery provides guidance on the management of perioperative bleeding risk and DOAC or VKA schedule, incorporating team-based decision-making, especially in high thrombotic risk patients or when undergoing procedures with higher risks of adverse outcome, should bleeding occur 1.
Management of Bleeding
- For severe bleeding, consider administering reversal agents like andexanet alfa (Andexxa) according to the dosing guidance provided in the 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants 1.
- Procedures with higher bleeding risks (eg, neuraxial anesthesia) should be performed with complete interruption of OAC.
- When minimal drug effect is desired, anticoagulants should be held, and the measurement of coagulation parameters, drug levels, or both may identify ongoing drug effects.
From the FDA Drug Label
As a result of FXa inhibition, apixaban prolongs clotting tests such as prothrombin time (PT), INR, and activated partial thromboplastin time (aPTT). Changes observed in these clotting tests at the expected therapeutic dose, however, are small, subject to a high degree of variability, and not useful in monitoring the anticoagulation effect of apixaban.
The effect of apixaban on PT/INR in patients with bleeding is not directly addressed in the provided drug labels. However, it is mentioned that apixaban prolongs clotting tests such as PT, INR, and aPTT, but these changes are small and not useful in monitoring the anticoagulation effect of apixaban.
- Key points:
- Apixaban inhibits FXa, which decreases thrombin generation and thrombus development.
- Apixaban prolongs clotting tests, but changes are small and variable.
- No direct information on the effect of apixaban on PT/INR in patients with bleeding. 2
From the Research
Management of Bleeding with Direct Oral Anticoagulants
- The management of bleeding in patients taking direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, and apixaban is a significant concern 3.
- Several studies have investigated the use of prothrombin complex concentrates (PCCs) to reverse the anticoagulant effect of DOACs in patients with major bleeding 4, 5, 6.
- The efficacy of PCCs in achieving clinical hemostasis in patients with major bleeding associated with apixaban or rivaroxaban has been reported to be around 65-78% 4, 5, 6.
- The use of specific reversal agents, such as andexanet alfa, has also been approved for the reversal of the anticoagulant effects of FXa inhibitors (rivaroxaban and apixaban) in patients with life-threatening or uncontrolled bleeding 7.
Risk Factors for Bleeding
- Certain situations are associated with a particularly high bleeding risk, including mild renal failure, advanced age, extremes in body weight, and drug-drug interactions, particularly with antiplatelet agents and nonsteroidal anti-inflammatory drugs 3.
- Concomitant use of medications that interact with DOACs can also increase the risk of bleeding 4.
Treatment Options
- Haemodialysis can reduce the plasma concentration of dabigatran, but rivaroxaban and apixaban cannot be eliminated by dialysis 3.
- Prothrombin complex concentrates and recombinant activated factor VII may have little or no efficacy in reversing the anticoagulant effect of DOACs, and they carry a poorly documented risk of thrombosis 3.
- Specific reversal agents, such as andexanet alfa, may provide improved strategies for the management of bleeding in patients taking DOACs 7.