Pharmacology Rounds: Andexanet Alfa and 4-Factor PCC
Sean Nordt and Megan Rech
- Factor Xa inhibitor (direct-acting oral anticoagulant) with critical bleeding and needs to be reversed
- 2 options: 4 factor prothrombin complex concentrate (PCC) or andexanet alfa
- DOACs inhibit factor Xa, which is toward the end of the cascade. It activates thrombin.
- The 2 most commonly used are apixaban and rivaroxaban.
- If it has an “XA” in the name, it is a Xa inhibitor
- If it has a “TR” in the name (eg, dabigatran), it is a direct thrombin inhibitor.
- A new factor 11a inhibitor is coming out, which will have “XIAN” in the name
- Are factor Xa inhibitors safe?
- Generally, yes, especially when compared to warfarin.
- Andexanet alfa acts as a decoy protein; it binds up the drug and removes it from circulation. It also has a pro-coagulant effect by increasing thrombin generation. This means it can be associated with thrombosis.
- It is important to know when the last dose was taken.
- If the patient has taken a dose within the last 24 hours, consider reversal in the setting of a life-threatening bleed.
- Patients with renal dysfunction may need reversal for up to 3 days.
- Can we test to see how anticoagulated they are? No. We can order the heparin-specific anti-Xa level, and some labs have this calibrated for these 2 drugs but most labs don’t. You could order it and get some information, but can’t get something like an international normalized ratio (INR).
- Efficacy: Andexanet alfa has an efficacy of about 80%; 4-factor PCC has about the same efficacy. The literature is weak.
- Both carry a thromboembolic risk. Andexanet alfa may be more pro-coagulant.
- Dosing regimens: Andexanet is given either as a high dose or low dose; PCC is given either as a weight-based dose or a fixed dose.
- Cost: Andexanet is about $12-15K a dose; 4-factor PCC is about $4-8K.
- Several professional organizations formally recommend giving andexanet alfa.
- The level of evidence is weak for both. Andexanet alfa has a slight edge on level of evidence.
CorePendium: Anticoagulant Reversal
EMA 2017 January: Andexanet Alfa For Acute Major Bleeding Associated With Factor Xa Inhibitors
EMA 2022 September: Andexanet Alfa vs 4F-PCC in Intracranial Bleed While on an "Xaban"
EMA 2019 January: Andexxa – An Antidote For Apixaban And Rivaroxaban
EMA 2020 August: Factor Xa inhibitor-related intracranial hemorrhage and PCC
EMA 2022 May: Anti-Factor Xa Levels to Guide Reversal of Factor Xa Inhibitors
EMA 2022 November: A Qualitative Point-of-Care Strip Test to Detect DOAC Exposure
EMA 2022 August: Oral factor XIa inhibitor Asundexian in A-Fib (PACIFIC-AF)