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The phase II Aspirin Regimens in EsSential thrombocythemia (ARES) trial has recently compared the efficacy of once\u2010 vs. twice\u2010 or three\u2010times daily low\u2010dose aspirin in inhibiting platelet thromboxane (TX) A<jats:sub>2<\/jats:sub> production, as reflected by serum (s) TXB<jats:sub>2<\/jats:sub> measurements. The present substudy characterized the determinants of the highly variable response to the standard aspirin 100\u00a0mg once\u2010daily regimen in fully compliant patients with ET and the effects of the experimental dosing regimens on response variability. By multivariable analysis, the platelet count (directly) and cytoreductive treatment (inversely) were significantly associated with sTXB<jats:sub>2<\/jats:sub> values in 218 patients with ET. However, the platelet count positively correlated with sTXB<jats:sub>2<\/jats:sub> in patients not being treated with cytoreductive drugs (\u03c1\u00a0=\u00a00.51, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01, <jats:italic>n<\/jats:italic>\u00a0=\u00a084), but not in patients on cytoreduction. Patients in the lowest sTXB<jats:sub>2<\/jats:sub> quartile were older, more often on cytoreductive drugs, had lower platelet count and Janus\u2010Associated Kinase<jats:italic>2 (JAK2)\u2010V617F<\/jats:italic> allele frequency as compared with patients in the upper sTXB<jats:sub>2<\/jats:sub> quartiles. After 2 weeks of a twice\u2010 or 3\u2010times daily aspirin regimen, the association between the platelet count and sTXB<jats:sub>2<\/jats:sub> became similar in cytoreduced and non\u2010cytoreduced patients. In conclusion, the platelet count appears the strongest determinant of TXA<jats:sub>2<\/jats:sub> inhibition by once\u2010daily low\u2010dose aspirin in ET, with different patterns depending of cytoreductive treatment. More frequent aspirin dosing restores adequate platelet inhibition and reduces interindividual variability, independently of cytoreduction.<\/jats:p>","DOI":"10.1002\/cpt.2485","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T13:50:52Z","timestamp":1636293052000},"page":"939-949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Association of Platelet Thromboxane Inhibition by Low\u2010Dose Aspirin With Platelet Count and Cytoreductive Therapy in Essential Thrombocythemia"],"prefix":"10.1111","volume":"111","author":[{"given":"Alberto","family":"Tosetto","sequence":"first","affiliation":[{"name":"Hematology Department Ospedale San Bortolo Vicenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8304-6423","authenticated-orcid":false,"given":"Bianca","family":"Rocca","sequence":"additional","affiliation":[{"name":"Department of Safety and Bioethics Section of Pharmacology Catholic University School of Medicine Rome Italy"},{"name":"Fondazione Policlinico Universitario A. 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