{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:03:30Z","timestamp":1789715010077,"version":"4.0.1"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The SAXOPHONE (Safety of Apixaban on Pediatric Heart Disease on the Prevention of Embolism) trial demonstrated the safety of apixaban for thromboprophylaxis in children with heart disease. Included a priori in the trial design was an exploratory biomarker substudy to evaluate the effects of apixaban on surrogate biomarkers of efficacy, thrombin generation capacity, and hemostatic proteins. The study assessed changes in\n                      <jats:sc>d<\/jats:sc>\n                      \u2010dimer, thrombin generation assay parameters, factor VIII, fibrinogen, protein C, and protein S in children receiving apixaban compared with standard\u2010of\u2010care vitamin K antagonists (VKAs) or low\u2010molecular\u2010weight heparin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">SAXOPHONE participants aged &gt;1\u2009year (n=182) had blood samples for biomarkers collected at baseline, week 2, or month 6. Participants were randomized to apixaban (n=123) or standard of care (VKA or low\u2010molecular\u2010weight heparin; n=59). Subgroup analyses accounted for prior VKA exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      <jats:sc>d<\/jats:sc>\n                      \u2010dimer levels decreased at month 6 in all treatment groups and remained stable during VKA\u2010to\u2010apixaban bridging. Apixaban significantly prolonged thrombin generation assay lag time and time to peak compared with VKAs and decreased peak thrombin similarly to VKAs in anticoagulant\u2010na\u00efve participants. Apixaban was associated with decreased fibrinogen and factor VIII at month 6, with no effect on protein C or S. Prior VKA exposure produced carryover effects, suppressing baseline\n                      <jats:sc>d<\/jats:sc>\n                      \u2010dimer, thrombin generation assay parameters, and proteins C and S.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Apixaban reduced hypercoagulability, as shown by decreased\n                      <jats:sc>d<\/jats:sc>\n                      \u2010dimer levels and prolonged lag time, and preserved endogenous thrombin potential in thrombin generation assay, changes consistent with adult data. These findings align with SAXOPHONE\u2019s primary outcomes, supporting apixaban\u2019s favorable risk\u2013benefit profile as a thromboprophylaxis option in children with heart disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.039075","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T09:47:26Z","timestamp":1774000046000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Ex Vivo Effect of Apixaban on Hemostatic Biomarkers in Children With Heart Disease: A SAXOPHONE Trial Substudy"],"prefix":"10.1161","volume":"15","author":[{"given":"Ghada A.","family":"Aborkhees","sequence":"first","affiliation":[{"name":"University of Alberta","place":["Edmonton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2514-2238","authenticated-orcid":false,"given":"Amy J.","family":"Barr","sequence":"additional","affiliation":[{"name":"University of Alberta","place":["Edmonton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Dietrich","sequence":"additional","affiliation":[{"name":"University of Alberta","place":["Edmonton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-6421","authenticated-orcid":false,"given":"Christoph","family":"Male","sequence":"additional","affiliation":[{"name":"Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1515-4945","authenticated-orcid":false,"given":"Zhaoqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb","place":["Lawrenceville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yao","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb","place":["Lawrenceville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-3628","authenticated-orcid":false,"given":"R. Mark","family":"Payne","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine","place":["Indianapolis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3791-8280","authenticated-orcid":false,"given":"Andrew C.","family":"Glatz","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["St. Louis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Monagle","sequence":"additional","affiliation":[{"name":"University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-1303","authenticated-orcid":false,"given":"Kristin M.","family":"Burns","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison 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