{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:35:54Z","timestamp":1787758554343,"version":"build-2784847793"},"reference-count":67,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006823","name":"Boston Children's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["5U01HL098147"],"award-info":[{"award-number":["5U01HL098147"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["5K08HL157653"],"award-info":[{"award-number":["5K08HL157653"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Children with heart disease face competing risks of thrombosis and bleeding. Antiplatelet agents are widely used, but clinical effectiveness and safety may vary with pharmacogenomic variants. We evaluated bleeding and thromboembolic outcomes and explored pharmacogenomic associations in a pediatric cardiac cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Single\u2010center, retrospective study of patients prescribed aspirin or clopidogrel during admissions (2011\u20132020). We abstracted clinical characteristics, pharmacodynamic testing, and adverse events while prescribed the antiplatelet agent through July 2021. Pharmacogenomic variants relevant to aspirin and clopidogrel metabolism\/function (including\n                      <jats:italic>CYP2C19<\/jats:italic>\n                      haplotypes and selected aspirin response loci) were called from existing genomic data. Outcomes included major bleeding and thromboembolism (TE) as well as pharmacodynamic aspirin \u201cresistance.\u201d Analyses were exploratory.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 105 patients treated with aspirin with VerifyNow pharmacodynamic and pharmacogenomic variant data and 49 clopidogrel\u2010treated patients with genetic data. Major bleeding occurred in 5% (aspirin) and 16% (clopidogrel); TE occurred in 12% and 8% of patients, respectively. On aspirin, bleeding was more frequent with renal (40% vs. 2%,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.011) or hepatic dysfunction (20% vs. 0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.048); TE was associated with younger age, lower weight, and single\u2010ventricle physiology. On clopidogrel, bleeding was associated with older age\/greater weight and renal dysfunction. No association was observed across CYP2C19 phenotypes and clopidogrel outcomes. No poor metabolizers were identified in this small cohort. Pharmacodynamic aspirin \u201cresistance\u201d was seen in 23% and was more common in females, with no association identified with TE. A\n                      <jats:italic>P2RY1<\/jats:italic>\n                      variant (rs1065776\u2010CT) was associated with the composite aspirin outcome of pharmacodynamic resistance and\/or TE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Clinically important bleeding and TE events were common in pediatric cardiac patients on antiplatelets, with organ dysfunction, age, and physiology emerging as key associations. Pharmacogenomic variants were frequent; a candidate\n                      <jats:italic>P2RY1<\/jats:italic>\n                      signal warrants validation. Pediatric antiplatelet management and relationships with outcomes are complex, supporting the need for prospective studies integrating pharmacogenomic variant analyses with standardized pharmacodynamic testing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70507","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T07:25:53Z","timestamp":1784964353000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bleeding and Thromboembolic Events With Antiplatelet Agents in Pediatric Heart Disease\u2014An Exploratory Study of the Role of Pharmacogenomics"],"prefix":"10.1002","volume":"73","author":[{"given":"Paul","family":"Esteso","sequence":"first","affiliation":[{"name":"Department of Pediatrics Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Cardiology Boston Children's Hospital  Boston Massachusetts 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