Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa
Introduction Andexanet alfa (andexanet) is an approved antidote used to reverse the bleeding effects of Direct Oral Anticoagulant (Direct-Xa agents) agents because it reverses anti-Xa activity. Unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) exhibit anti-Xa activity. The purpo...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-05-01
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| Series: | Clinical and Applied Thrombosis/Hemostasis |
| Online Access: | https://doi.org/10.1177/10760296221099934 |
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| author | Joseph Lewis BA Omer Iqbal MD Walter Jeske PhD Debra Hoppensteadt PhD Fakiha Siddiqui BDS Jawed Fareed PhD |
| author_facet | Joseph Lewis BA Omer Iqbal MD Walter Jeske PhD Debra Hoppensteadt PhD Fakiha Siddiqui BDS Jawed Fareed PhD |
| author_sort | Joseph Lewis BA |
| collection | DOAJ |
| description | Introduction Andexanet alfa (andexanet) is an approved antidote used to reverse the bleeding effects of Direct Oral Anticoagulant (Direct-Xa agents) agents because it reverses anti-Xa activity. Unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) exhibit anti-Xa activity. The purpose is to investigate the neutralization of UFH and LMWH by andexanet in activated clotting time (ACT), thrombelastography (TEG), and anti-Xa due to the protamine sulfate shortage. Methods UFH and LMWH were studied with andexanet, PS, or saline as potential reversal agents/controls at varying concentrations in ACT, TEG, and anti-Xa and compared to each other. Results Andexanet partially neutralized both drugs several TEG parameters at high andexanet concentrations, but it was not as effective as protamine sulfate in any of the assays used. Most TEG parameters were correlated with andexanet concentration. In ACT, significant neutralization was demonstrated at many andexanet concentrations for UFH, but not LMWH. UFH was completely neutralized by PS in ACT, while LMWH was partially neutralized by PS in ACT. Andexanet alfa was a less effective neutralization agent than the protamine sulfate as it only partially neutralized UFH in ACT and was ineffective at neutralizing LMWH when tested at the same concentration as PS (10 ug/mL). Conclusion Andexanet partially neutralized UFH and LMWH with variability between assays, necessitating investigation into assay-dependent differences. |
| first_indexed | 2024-04-14T00:01:24Z |
| format | Article |
| id | doaj.art-898573021cb94fc8992380467d649964 |
| institution | Directory Open Access Journal |
| issn | 1938-2723 |
| language | English |
| last_indexed | 2024-04-14T00:01:24Z |
| publishDate | 2022-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical and Applied Thrombosis/Hemostasis |
| spelling | doaj.art-898573021cb94fc8992380467d6499642022-12-22T02:23:41ZengSAGE PublishingClinical and Applied Thrombosis/Hemostasis1938-27232022-05-012810.1177/10760296221099934Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet AlfaJoseph Lewis BA0Omer Iqbal MD1Walter Jeske PhD2Debra Hoppensteadt PhD3Fakiha Siddiqui BDS4Jawed Fareed PhD5 Cardiovascular Research Institute, , Health Sciences Divisions, Maywood, IL, USA Cardiovascular Research Institute, , Health Sciences Divisions, Maywood, IL, USA Cardiovascular Research Institute, , Health Sciences Divisions, Maywood, IL, USA Cardiovascular Research Institute, , Health Sciences Divisions, Maywood, IL, USA Program in Health Science, Universidad Católica de Murcia, Spain Cardiovascular Research Institute, , Health Sciences Divisions, Maywood, IL, USAIntroduction Andexanet alfa (andexanet) is an approved antidote used to reverse the bleeding effects of Direct Oral Anticoagulant (Direct-Xa agents) agents because it reverses anti-Xa activity. Unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) exhibit anti-Xa activity. The purpose is to investigate the neutralization of UFH and LMWH by andexanet in activated clotting time (ACT), thrombelastography (TEG), and anti-Xa due to the protamine sulfate shortage. Methods UFH and LMWH were studied with andexanet, PS, or saline as potential reversal agents/controls at varying concentrations in ACT, TEG, and anti-Xa and compared to each other. Results Andexanet partially neutralized both drugs several TEG parameters at high andexanet concentrations, but it was not as effective as protamine sulfate in any of the assays used. Most TEG parameters were correlated with andexanet concentration. In ACT, significant neutralization was demonstrated at many andexanet concentrations for UFH, but not LMWH. UFH was completely neutralized by PS in ACT, while LMWH was partially neutralized by PS in ACT. Andexanet alfa was a less effective neutralization agent than the protamine sulfate as it only partially neutralized UFH in ACT and was ineffective at neutralizing LMWH when tested at the same concentration as PS (10 ug/mL). Conclusion Andexanet partially neutralized UFH and LMWH with variability between assays, necessitating investigation into assay-dependent differences.https://doi.org/10.1177/10760296221099934 |
| spellingShingle | Joseph Lewis BA Omer Iqbal MD Walter Jeske PhD Debra Hoppensteadt PhD Fakiha Siddiqui BDS Jawed Fareed PhD Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa Clinical and Applied Thrombosis/Hemostasis |
| title | Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa |
| title_full | Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa |
| title_fullStr | Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa |
| title_full_unstemmed | Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa |
| title_short | Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa |
| title_sort | differential neutralization of unfractionated heparin and enoxaparin by andexanet alfa |
| url | https://doi.org/10.1177/10760296221099934 |
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