April 2021 Quick Question: Andexanet Alfa

April 2021 Quick Question: Andexanet Alfa
Mar 30, 2021 4:17pm

Our April Quick Question arises from discussions with Chad Siniard, MD., University of Alabama at Birmingham Division of Laboratory Medicine and hemostasis author and expert Dave McGlasson. Andexanet Alfa® is the FDA-approved reversal agent for rivaroxaban and apixaban that has become a standard ER treatment for potential anticoagulant overdose. A key consideration is the US cost, approximately $30,000 per dose. Laboratory directors around the US have specified a laboratory assay confirming the presence of anticoagulant therapy prior to Andexanet administration. Our question asks what assay facilities are using and what assay is the most appropriate.

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Our April Quick Question arises from discussions with Chad Siniard, MD., University of Alabama at Birmingham Division of Laboratory Medicine and hemostasis author and expert Dave McGlasson. Andexanet Alfa® is the FDA-approved reversal agent for rivaroxaban and apixaban that has become a standard ER treatment for potential anticoagulant overdose. A key consideration is the US cost, approximately $30,000 per dose. Laboratory directors around the US have specified a laboratory assay confirming the presence of anticoagulant therapy prior to Andexanet administration. Our question asks what assay facilities are using and what assay is the most appropriate.

By Bob
Apr 6, 2021 6:26pm
From Bob Gosselin. What they are using and consider most appropriate seem contrary to the US prescribing information for Andexanet, which is based on whether the last dose exposure is known or unknown.
Theoretically, a rapid test using modified or dedicated anti-Xa tests, which are cheap and fast and can be performed on most automated coagulation analyzers would be the best candidate to rapidly measure anti-factor Xa DOACs such as apixaban, edoxaban or rivaroxaban [betrixaban was pulled from the market in May 2020]. This could be accomplished using drug calibrated [for accuracy] or "guesstimations" or binary results using heparin-type calibrated assays. Note that drug calibration for any specific heparin or DOAC does not increase specificity as all drugs in this class will have an additive effect to the results when using anti-Xa methods.
I believe there are some articles or organizations suggesting that presence or greater than 50 ng/mL in a bleeding patient warrant reversal agents. The other platforms to assess DOACs, include modified thromboelastography such as the TEG 6S, and point-of-care technologies have been described, but not sure where they are in the regulatory approval process.

Post treatment measurements of anti-Xa have not been advocated due to lack of correlation of these post-Rx anti-Xa measurements with clinical outcomes. Additionally, it was initially reported that there is a dissociation with Andexanet Alfa after several hours, but that was a bias created by a method with a high sample pre-dilution [~1:30] so methods using lower sample pre-dilutions [~1:8] would be more representative of post-treatment levels, should those be a clinician desired test request.

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