{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T14:53:18Z","timestamp":1775055198407,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T00:00:00Z","timestamp":1426032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Valproic acid (<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>) is an antiepileptic drug that has been associated with impaired hemostasis and increased risk for postsurgical bleeding. However, the published reports provide controversial results. We measured parameters of primary hemostasis in <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010treated patients with epilepsy, focusing on adenosine nucleotide\u2013dependent platelet responses, which play a central role in primary hemostasis. We enrolled 20 cases (epileptic patients receiving treatment with <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>) and 20 controls (12 epileptic patients receiving treatment with drugs different from <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> and 8 healthy subjects). Measurements included prothrombin time (<jats:styled-content style=\"fixed-case\">PT<\/jats:styled-content>), activated partial thromboplastin time (<jats:styled-content style=\"fixed-case\">APTT<\/jats:styled-content>), platelet count, platelet function analyzer (<jats:styled-content style=\"fixed-case\">PFA<\/jats:styled-content>)\u2010100 closure times, plasma von Willebrand factor levels, platelet content of <jats:styled-content style=\"fixed-case\">ADP<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> ATP<\/jats:styled-content>, and serotonin (all stored in platelet dense granules), and platelet shape change and aggregation induced by <jats:styled-content style=\"fixed-case\">ADP<\/jats:styled-content> and other platelet agonists, including the <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> analog \u03b1,\u03b2\u2010methylene\u2010<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>. The plasma concentration of <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> was in the therapeutic range in 17 patients and slightly above the upper limit in 3 patients. There were no statistically significant differences in any of the studied parameters in cases versus controls. Our thorough controlled study failed to show that chronic treatment with <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> induces significant abnormalities of coagulation and primary hemostasis. Therefore, <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>, when present in the circulation in the therapeutic range, does not impair hemostasis.<\/jats:p>","DOI":"10.1111\/epi.12952","type":"journal-article","created":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T09:25:45Z","timestamp":1426065945000},"source":"Crossref","is-referenced-by-count":21,"title":["Effects of chronic administration of valproic acid to epileptic patients on coagulation tests and primary hemostasis"],"prefix":"10.1111","volume":"56","author":[{"given":"Maddalena L.","family":"Zighetti","sequence":"first","affiliation":[{"name":"Medicine Unit 3 San Paolo Hospital Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gessica","family":"Fontana","sequence":"additional","affiliation":[{"name":"Medicine Unit 3 San Paolo Hospital Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Lussana","sequence":"additional","affiliation":[{"name":"Medicine Unit 3 San Paolo Hospital Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Chiesa","sequence":"additional","affiliation":[{"name":"Neurology Unit 2 Epilepsy Center San Paolo Hospital Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aglaia","family":"Vignoli","sequence":"additional","affiliation":[{"name":"Neurology Unit 2 Epilepsy Center San Paolo Hospital Milan Italy"},{"name":"Department of Health Sciences University of Milan Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Paola","family":"Canevini","sequence":"additional","affiliation":[{"name":"Neurology Unit 2 Epilepsy Center San Paolo Hospital Milan Italy"},{"name":"Department of Health Sciences University of Milan Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Medicine Unit 3 San Paolo Hospital Milan Italy"},{"name":"Department of Health Sciences University of Milan Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,3,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/157488609789006976"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03008150"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2006.07.058"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2003.11.001"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1997.87.2.0252"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1996.tb00519.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1992.tb02303.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389400900318"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1981.tb04094.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)91308-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-387837-3.00014-6"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-263111"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02752.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12231"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1220324"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.12952","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.12952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T14:08:35Z","timestamp":1695478115000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.12952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,11]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1111\/epi.12952"],"URL":"https:\/\/doi.org\/10.1111\/epi.12952","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,11]]}}}