{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:54:12Z","timestamp":1791986052009,"version":"4.4.0"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35HL144993"],"award-info":[{"award-number":["R35HL144993"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08HD111687\u201001A1"],"award-info":[{"award-number":["K08HD111687\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pregnancy"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Platelet hyperreactivity is linked to inflammation and cardiovascular risk in nonpregnant populations, but its relationship to placentally mediated pregnancy outcomes is undefined. We prospectively evaluated platelet hyperreactivity in pregnancy and subsequent ischemic placental disease (IPD), and examined aspirin's (ASA) effect on platelet activity by baseline platelet phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Pregnancy Outcomes and Platelet PhenotYpes (POPPY) was a prospective cohort study with blood collection in the first and second trimesters. Platelet function was assessed via light transmission aggregometry (LTA) and platelet hyperreactivity was defined a priori as\u00a0&gt;60% aggregation in response to 0.4\u00a0\u00b5M epinephrine. The primary outcome was a composite IPD endpoint (hypertensive disorders of pregnancy [HDP], placental abruption, small\u2010for\u2010gestational\u2010age [SGA] birth, and stillbirth). We used multivariable logistic regression to estimate the association between baseline platelet hyperreactivity and IPD. In addition, first\u2010trimester platelet transcriptome (pre\u2010ASA) was compared between participants with and without platelet hyperreactivity. In a high\u2010risk subset defined per US Preventative Task Force criteria and recommended ASA 81\u00a0mg daily, we evaluated ASA's effects on serum thromboxane (TxB2) and platelet aggregation by hyperreactivity status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 66 pregnant participants recruited, 61 had first\u2010trimester LTA; 20 (32.8%) had platelet hyperreactivity. Participants with hyperreactivity were more likely to develop IPD than those without (55% vs. 24%; adjusted odds ratio [aOR], 3.77; 95% confidence interval [CI], 1.05\u201313.53), with consistent directionality across individual components despite low event frequencies. Participants with platelet hyperreactivity showed greater platelet aggregation to adenosine diphosphate (ADP), collagen, and low\u2010dose arachidonic acid (AA). Platelet transcriptomic profiling distinguished participants with versus without platelet hyperreactivity and revealed differential expression of pathways related to platelet activity, energy metabolism, and immune regulation. Among 45 high\u2010risk participants recommended ASA, those with hyperreactivity exhibited higher AA\u2010induced aggregation (24%\u00a0vs. 12.5% platelet aggregation,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.01) despite similar serum TxB2 levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>First\u2010trimester platelet hyperreactivity was present in approximately one third of the participants and was independently associated with increased risk of IPD. Participants with platelet hyperreactivity demonstrated distinct transcriptomic signatures and greater platelet aggregation despite ASA use. Together, these findings support a contributory role for platelets in placental ischemic pathology and highlight the need to elucidate mechanisms and develop platelet\u2010targeted preventive strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov identifier: NCT06194643.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pmf2.70255","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:02:36Z","timestamp":1770969756000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Platelet hyperreactivity and risk of ischemic placental disease: A prospective cohort study"],"prefix":"10.1002","volume":"2","author":[{"given":"Christina A.","family":"Penfield","sequence":"first","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine, Department of Obstetrics and Gynecology NYU Grossman School of Medicine  New York New York USA"},{"name":"Department of Obstetrics and Gynecology NYU Langone Health  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre A.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine, Department of Obstetrics and Gynecology NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Schaap","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Luttrell\u2010Williams","sequence":"additional","affiliation":[{"name":"Leon H. Charney Division of Cardiology, Department of Medicine NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anais","family":"Hausvater","sequence":"additional","affiliation":[{"name":"Leon H. Charney Division of Cardiology, Department of Medicine NYU Grossman School of Medicine  New York New York USA"},{"name":"Sarah Ross Soter Center for Women's Cardiovascular Research NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhe","family":"Xia","sequence":"additional","affiliation":[{"name":"Division of Biostatistics NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Muller","sequence":"additional","affiliation":[{"name":"Leon H. Charney Division of Cardiology, Department of Medicine NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison S.","family":"House","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeryia","family":"Avtushka","sequence":"additional","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine, Department of Obstetrics and Gynecology NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lila","family":"Murphy","sequence":"additional","affiliation":[{"name":"Leon H. Charney Division of Cardiology, Department of Medicine NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarice G.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine, Department of Obstetrics and Gynecology NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin S.","family":"Brandt","sequence":"additional","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine, Department of Obstetrics and Gynecology NYU Grossman School of Medicine  New York New York USA"},{"name":"Department of Obstetrics and Gynecology NYU Langone Health  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendolyn P.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley S.","family":"Roman","sequence":"additional","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine, Department of Obstetrics and Gynecology NYU Grossman School of Medicine  New York New York USA"},{"name":"Department of Obstetrics and Gynecology NYU Langone Health  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana R.","family":"Gossett","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology NYU Langone Health  New York New York USA"},{"name":"Department of Obstetrics and Gynecology NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Berger","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine NYU Grossman School of Medicine  New York New York USA"},{"name":"Leon H. 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