{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:10:27Z","timestamp":1777479027067,"version":"3.51.4"},"reference-count":22,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clin Appl Thromb Hemost"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Andexanet alfa (AA) - zhzo, recombinant coagulation factor Xa, is an approved antidote for oral Xa inhibitors (apixaban and rivaroxaban). Unfractionated heparin (UFH) is commonly used for therapeutic, interventional, and surgical indications. Protamine sulfate (PrSO\n                      <jats:sub>4<\/jats:sub>\n                      ) is frequently used to neutralize UFH. This study aimed to investigate the comparative neutralization profiles of AA and PrSO\n                      <jats:sub>4<\/jats:sub>\n                      for heparins of bovine, ovine, and porcine origin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      The neutralization effect of PrSO\n                      <jats:sub>4<\/jats:sub>\n                      at 25 \u00b5g\/ml and AA at 100 \u00b5g\/ml was studied on an approximate surgical\/interventional concentration of heparin by supplementing whole blood with each of the heparins at 25 \u00b5g\/ml. For the clotting profile (activated partial thromboplastin time: aPTT), amidolytic (anti-Xa and anti-IIa), and thrombin generation assay each of the heparin were supplemented from \u201310\u20130.62 \u00b5g\/ml.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the whole blood ACT studies, all three heparins produced strong anti-coagulant effects (400\u2013450\u2005seconds) compared to saline (130\u2013150\u2005seconds). Both AA and PrSO\n                      <jats:sub>4<\/jats:sub>\n                      almost fully neutralized the anti-coagulant effects of heparins (140\u2013160\u2005seconds). Both antidotes completely reversed the anticoagulant effects of all three heparins in the aPTT and thrombin generation assay. However, PrSO\n                      <jats:sub>4<\/jats:sub>\n                      was more effective in neutralizing the anti-Xa, and anti-IIa effects than AA, which only partially neutralized these effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Andexanet alfa at 100 \u00b5g\/ml effectively neutralizes the therapeutic and surgical\/interventional concentrations of heparins in in-vitro settings. While differences in the anti-Xa, and anti-IIa effects between heparins were noted, anti-coagulant effect of these agents in the aPTT assay were comparable. A similar neutralization profile was observed in the ACT and thrombin generation assays by both agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10760296241247558","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T09:06:56Z","timestamp":1713949616000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Andexanet Alfa Neutralizes the Anticoagulant Effects of Unfractionated Heparin of Bovine, Ovine and Porcine Origin Almost as Protamine Sulfate"],"prefix":"10.1177","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2219-7049","authenticated-orcid":false,"given":"Fakiha","family":"Siddiqui","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute, Loyola University Chicago, Health Sciences Division, Maywood, IL, USA"},{"name":"Program in Health Sciences, UCAM - Universidad Cat\u00f3lica San Antonio de Murcia, Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9342-4213","authenticated-orcid":false,"given":"Debra","family":"Hoppensteadt","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Loyola University Chicago, Health Sciences Division, Maywood, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Jeske","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Loyola University Chicago, Health Sciences Division, Maywood, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5735-1333","authenticated-orcid":false,"given":"Eduardo","family":"Ramacciotti","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Loyola University Chicago, Health Sciences Division, Maywood, IL, USA"},{"name":"Science Valley Research Institute, S\u00e3o Paulo, SP, Brazil"},{"name":"Hospital e Maternidade Christ\u00f3v\u00e3o da Gama, Grupo DASA, Santo Andre, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Tafur","sequence":"additional","affiliation":[{"name":"Northshore Cardiovascular Institute, NorthShore University Health Systems, Evanston, IL, USA"},{"name":"Pritzker School of Medicine, University of Chicago, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-2499","authenticated-orcid":false,"given":"Jawed","family":"Fareed","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Loyola University Chicago, Health Sciences Division, Maywood, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"issue":"3","key":"bibr1-10760296241247558","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3390\/ph9030038","volume":"9","author":"Oduah EI","year":"2016","journal-title":"Pharmaceuticals (Basel)"},{"issue":"1","key":"bibr2-10760296241247558","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/ccd.30679","volume":"102","author":"Danek BA","year":"2023","journal-title":"Catheter Cardiovasc Interv"},{"issue":"4","key":"bibr3-10760296241247558","first-page":"659","volume":"40","author":"Carr JA","year":"1999","journal-title":"J Cardiovasc Surg (Torino)"},{"issue":"4","key":"bibr4-10760296241247558","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nm.3102","volume":"19","author":"Lu G","year":"2013","journal-title":"Nat Med"},{"key":"bibr5-10760296241247558","unstructured":"Pharmaceuticals. P. U.S. FDA approves Portola Pharmaceuticals Andexxa\u00ae, the first and only antidote for the reversal of factor Xa inhibitors. 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