{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:27:58Z","timestamp":1774744078609,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Low\u2010dose aspirin is currently recommended for patients with polycythemia vera (PV), a myeloproliferative neoplasm with increased risk of arterial and venous thromboses. Based on aspirin pharmacodynamics in essential thrombocythemia, a twice\u2010daily regimen is recommended for patients with PV deemed at particularly high thrombotic risk. We investigated the effects of low\u2010dose aspirin on platelet cyclooxygenase activity and in vivo platelet activation in 49 patients with PV, as assessed by serum thromboxane (TX) B<jats:sub>2<\/jats:sub> and urinary TXA<jats:sub>2<\/jats:sub>\/TXB<jats:sub>2<\/jats:sub> metabolite (TXM) measurements, respectively. A previously described pharmacokinetic\u2010pharmacodynamic in silico model was used to simulate the degree of platelet TXA<jats:sub>2<\/jats:sub> inhibition by once\u2010daily (q.d.) and twice\u2010daily (b.i.d.) aspirin, and to predict the effect of missing an aspirin dose during q.d. and b.i.d. regimens. Serum TXB<jats:sub>2<\/jats:sub> averaged 8.2 (1.6\u201354.7) ng\/ml and significantly correlated with the platelet count (<jats:italic>\u03b3<\/jats:italic>\u00a0=\u00a00.39) and urinary TXM (<jats:italic>\u03b3<\/jats:italic>\u00a0=\u00a00.52) in multivariable analysis. One\u2010third of aspirin\u2010treated patients with PV displayed less\u2010than\u2010maximal platelet TXB<jats:sub>2<\/jats:sub> inhibition, and were characterized by significantly higher platelet counts and platelet\u2010count corrected serum TXB<jats:sub>2<\/jats:sub> than those with adequate inhibition. Eight patients with PV were sampled again after 12\u2009\u00b1\u20094\u00a0months, and had reproducible serum TXB<jats:sub>2<\/jats:sub> and urinary TXM values. The in silico model predicted complete inhibition of platelet\u2010derived TXB<jats:sub>2<\/jats:sub> by b.i.d. aspirin, a prediction verified in a patient with PV with the highest TXB<jats:sub>2<\/jats:sub> value while on aspirin q.d. and treated short\u2010term with a b.i.d. regimen. In conclusion, one in three patients with PV on low\u2010dose aspirin display less\u2010than\u2010maximal inhibition of platelet TXA<jats:sub>2<\/jats:sub> production. Serum TXB<jats:sub>2<\/jats:sub> measurement can be a valuable option to guide precision dosing of antiplatelet therapy in patients with PV.<\/jats:p>","DOI":"10.1111\/cts.13415","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T06:43:25Z","timestamp":1665038605000},"page":"2958-2970","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Platelet thromboxane inhibition by low\u2010dose aspirin in polycythemia vera: Ex vivo and in vivo measurements and in silico simulation"],"prefix":"10.1111","volume":"15","author":[{"given":"Giovanna","family":"Petrucci","sequence":"first","affiliation":[{"name":"Department of Safety and Bioethics, Section of Pharmacology Catholic University School of Medicine  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Giaretta","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Ranalli","sequence":"additional","affiliation":[{"name":"Department of Hematology S. Spirito Hospital  Pescara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviana","family":"Cavalca","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Dragani","sequence":"additional","affiliation":[{"name":"Department of Hematology S. Spirito Hospital  Pescara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedetta","family":"Porro","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duaa","family":"Hatem","sequence":"additional","affiliation":[{"name":"Department of Safety and Bioethics, Section of Pharmacology Catholic University School of Medicine  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6027-0043","authenticated-orcid":false,"given":"Aida","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, QU Health Qatar University  Doha Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Tremoli","sequence":"additional","affiliation":[{"name":"Maria Cecilia Hospital  Cotignola Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Patrono","sequence":"additional","affiliation":[{"name":"Department of Safety and Bioethics, Section of Pharmacology Catholic University School of Medicine  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-10-429134"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.57.6652"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5387-9"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.7326\/M17-0284"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26008"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035572"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1208500"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-359224"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.694"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2011.09.017"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004596"},{"key":"e_1_2_9_13_1","unstructured":"http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2009\/09\/WC500003340.pdf."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(80)90066-3"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH16-05-0349"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(87)90233-5"},{"key":"e_1_2_9_17_1","first-page":"94","article-title":"Immunological characterization of urinary 8\u2010epi\u2010prostaglandin F2 alpha excretion in man","volume":"275","author":"Wang Z","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH13-10-0844"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.10.047"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1649916"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2016-203625"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abd3139"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14445"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.362682.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V80.8.1965.1965"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2012.04723.x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01244"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab003"},{"key":"e_1_2_9_29_1","doi-asserted-by":"crossref","unstructured":"Zaccardi F.et al.In vivo platelet activation and aspirin responsiveness in type 1 diabetes.Diabetes65 503\u20139(2016).","DOI":"10.2337\/db15-0936"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2013.05.003"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2016.04.006"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2018.05.009"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2010.06.014"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0b013e328364713a"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.72.6.1177"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110576"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000013777.21160.07"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12753"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1013"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1933"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14619"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13050709"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25303"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1981.tb01244.x"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-008-0499-1"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-4310(98)01372-0"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3233\/CH-170304"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01170-z"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/102476"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-394775"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.101895"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15476"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13415","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.13415","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13415","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T19:29:49Z","timestamp":1694892589000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13415"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,5]]},"references-count":51,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1111\/cts.13415"],"URL":"https:\/\/doi.org\/10.1111\/cts.13415","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,5]]},"assertion":[{"value":"2021-10-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}