{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T04:57:30Z","timestamp":1773982650288,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T00:00:00Z","timestamp":1720915200000},"content-version":"vor","delay-in-days":195,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004434","name":"Universit\u00e0 degli Studi di Firenze","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004434","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> In February 2021, a few cases of unusual, severe thrombotic events associated with thrombocytopenia reported after vaccination with ChAdOx1 nCoV\u201019 (Vaxzevria) or with Johnson &amp; Johnson\u2019s Janssen vaccine raise concern about safety. The vaccine\u2010induced thrombotic thrombocytopenia (VITT) has been related to the presence of platelet\u2010activating antibodies directed against platelet Factor 4.<\/jats:p><jats:p><jats:bold>Objectives:<\/jats:bold> We investigated VITT subject genetic background by a high\u2010throughput whole exome sequencing (WES) approach in order to investigate VITT genetic predisposition.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Six consecutive patients (females of Caucasian origin with a mean age of 64 years) were referred to the Atherothrombotic Diseases Center (Department of Experimental and Clinical Medicine, Azienda Ospedaliero\u2010Universitaria Careggi, Florence) with a diagnosis of definite VITT underwent WES analysis. WES analysis was performed on the Illumina NextSeq500 platform.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold>WES analysis revealed a total of 140,563 genetic variants. Due to VITT\u2019s rare occurrence, we focused attention on rare variants. The global analysis of all high\u2010quality rare variants did not reveal a significant enrichment of mutated genes in biological\/functional pathways common to patients analyzed. Afterwards, we focused on rare variants in genes associated with blood coagulation and fibrinolysis, platelet activation and aggregation, integrin\u2010mediated signaling pathway, and inflammation with particular attention to those involved in vascular damage, as well as autoimmune thrombocytopenia. According to ACMG criteria, 47\/194 (24.2%) rare variants were classified as uncertain significance variants (VUS), whereas the remaining were likely benign\/benign.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> WES analysis identifies rare variants possibly favoring the prothrombotic state triggered by the exposure to the vaccine. Functional studies and\/or extensions to a larger number of patients might allow a more comprehensive definition of these molecular pathways.<\/jats:p>","DOI":"10.1155\/2024\/2860547","type":"journal-article","created":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T16:18:47Z","timestamp":1720973927000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Whole Exome Sequencing in Vaccine\u2010Induced Thrombotic Thrombocytopenia (VITT)"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8708-9444","authenticated-orcid":false,"given":"Betti","family":"Giusti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0990-4618","authenticated-orcid":false,"given":"Elena","family":"Sticchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0158-207X","authenticated-orcid":false,"given":"Tommaso","family":"Capezzuoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2251-4435","authenticated-orcid":false,"given":"Rebecca","family":"Orsi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9419-0812","authenticated-orcid":false,"given":"Lapo","family":"Squillantini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0045-9191","authenticated-orcid":false,"given":"Marco","family":"Giannini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuele","family":"Suraci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela Antonietta","family":"Rogolino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3616-6219","authenticated-orcid":false,"given":"Francesca","family":"Cesari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Berteotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6857-5861","authenticated-orcid":false,"given":"Anna Maria","family":"Gori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Lotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9549-7176","authenticated-orcid":false,"given":"Rossella","family":"Marcucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,14]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-021-02793-x"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab592"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03385.x"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13813"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109908"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.7517"},{"key":"e_1_2_11_7_2","unstructured":"EMA news http:\/\/www.ema.europa.eu\/en\/documents\/referral\/use-vaxzevria-prevent-covid-19-article-53-procedure-assessment-report_en.pdf."},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.728513"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-01-478966"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.13629"},{"key":"e_1_2_11_11_2","article-title":"Thrombotic thrombocytopenia after ChAdOx1 nCoV-19 vaccination","volume":"385","author":"Choi P. 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