{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T23:22:35Z","timestamp":1756682555093,"version":"3.41.2"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013120","name":"European Medicines Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013120","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Thrombosis with thrombocytopenia syndrome (TTS) has been identified as a rare adverse event following some COVID-19 vaccines. Various guidelines have been issued on the treatment of TTS. We aimed to characterize the treatment of TTS and other thromboembolic events (venous thromboembolism (VTE), and arterial thromboembolism (ATE) after COVID-19 vaccination and compared to historical (pre-vaccination) data in Europe and the US.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We conducted an international network cohort study using 8 primary care, outpatient, and inpatient databases from France, Germany, Netherlands, Spain, The United Kingdom, and The United States. We investigated treatment pathways after the diagnosis of TTS, VTE, or ATE for a pre-vaccination (background) cohort (01\/2017\u201411\/2020), and a vaccinated cohort of people followed for 28\u00a0days after a dose of any COVID-19 vaccine recorded from 12\/2020 onwards).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Great variability was observed in the proportion of people treated (with any recommended therapy) across databases, both before and after vaccination. Most patients with TTS received heparins, platelet aggregation inhibitors, or direct Xa inhibitors. The majority of VTE patients (before and after vaccination) were first treated with heparins in inpatient settings and direct Xa inhibitors in outpatient settings. In ATE patients, treatments were also similar before and after vaccinations, with platelet aggregation inhibitors prescribed most frequently. Inpatient and claims data also showed substantial heparin use.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> TTS, VTE, and ATE after COVID-19 vaccination were treated similarly to background events. Heparin use post-vaccine TTS suggests most events were not identified as vaccine-induced thrombosis with thrombocytopenia by the treating clinicians.<\/jats:p>","DOI":"10.3389\/fphar.2023.1118203","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T04:44:48Z","timestamp":1679633088000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterising the treatment of thromboembolic events after COVID-19 vaccination in 4 European countries and the US: An international network cohort study"],"prefix":"10.3389","volume":"14","author":[{"given":"Aniek F.","family":"Markus","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria Y.","family":"Strauss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Burn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xintong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Delmestri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Reich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Can","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A.","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan-Manuel","family":"Ram\u00edrez-Anguita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edelmira","family":"Marti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia M. C.","family":"Verhamme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter R.","family":"Rijnbeek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Prieto-Alhambra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika M.","family":"J\u00f6dicke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/nejmoa2035389","article-title":"Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"7169","DOI":"10.1038\/s41467-022-34669-9","article-title":"Thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in Catalonia, Spain","volume":"13","author":"Burn","year":"2022","journal-title":"Nat. Commun."},{"key":"B3","doi-asserted-by":"publisher","first-page":"7167","DOI":"10.1038\/s41467-022-34668-w","article-title":"Thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in the United Kingdom","volume":"13","author":"Burn","year":"2022","journal-title":"Nat. Commun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1056\/NEJMe2106315","article-title":"SARS-CoV-2 vaccine\u2013induced immune thrombotic thrombocytopenia","volume":"384","author":"Cines","year":"2021","journal-title":"NEJM"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1056\/NEJMoa2104840","article-title":"Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination","volume":"384","author":"Greinacher","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"281","DOI":"10.2450\/2021.0117-21","article-title":"Management of cerebral and splanchnic vein thrombosis associated with thrombocytopenia in subjects previously vaccinated with vaxzevria (AstraZeneca): A position statement from the Italian society for the study of haemostasis and thrombosis (SISET)","volume":"19","author":"Gresele","year":"2021","journal-title":"Blood Transfus."},{"key":"B7","doi-asserted-by":"publisher","first-page":"n1931","DOI":"10.1136\/bmj.n1931","article-title":"Risk of thrombocytopenia and thromboembolism after Covid-19 vaccination and SARS-CoV-2 positive testing: Self-controlled case series study","volume":"374","author":"Hippisley-Cox","year":"2021","journal-title":"BMJ"},{"key":"B8","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1093\/eurheartj\/ehx393","article-title":"2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)","volume":"39","author":"Ibanez","year":"2017","journal-title":"Eur. Heart J."},{"key":"B9","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1080\/00325481.2021.1891788","article-title":"Prophylaxis and treatment of COVID-19 related venous thromboembolism","volume":"133","author":"Kaptein","year":"2021","journal-title":"Postgrad. Med."},{"key":"B10","doi-asserted-by":"crossref","DOI":"10.1101\/2022.01.24.22269588","article-title":"TreatmentPatterns: An R package to analyze treatment patterns of a study population of interest","author":"Markus","year":"2022"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1111\/jth.15341","article-title":"Recommendations for the clinical and laboratory diagnosis of VITT against COVID-19: Communication from the ISTH SSC subcommittee on platelet immunology","volume":"19","author":"Nazy","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"B12","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1055\/a-1469-7481","article-title":"Diagnosis and management of vaccine-related thrombosis following AstraZeneca COVID-19 vaccination: Guidance statement from the GTH","volume":"41","author":"Oldenburg","year":"2021","journal-title":"Hamostaseologie"},{"key":"B13","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1136\/amiajnl-2011-000376","article-title":"Validation of a common data model for active safety surveillance research","volume":"19","author":"Overhage","year":"2012","journal-title":"J. Am. Med. Inf. Assoc."},{"key":"B14","doi-asserted-by":"publisher","first-page":"n2195","DOI":"10.1136\/bmj.n2195","article-title":"Vaccine induced immune thrombocytopenia and thrombosis: Summary of NICE guidance","volume":"375","author":"Pavord","year":"2021","journal-title":"BMJ"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"n1114","DOI":"10.1136\/bmj.n1114","article-title":"Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: Population based cohort study","volume":"373","author":"Pottegard","year":"2021","journal-title":"BMJ"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1001\/jamacardio.2021.3444","article-title":"Clinical characteristics and pharmacological management of COVID-19 vaccine-induced immune thrombotic thrombocytopenia with cerebral venous sinus thrombosis: A review","volume":"6","author":"Rizk","year":"2021","journal-title":"JAMA Cardiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.1056\/NEJMoa2104882","article-title":"Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination","volume":"384","author":"Schultz","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2202","DOI":"10.1056\/NEJMoa2105385","article-title":"Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination","volume":"384","author":"Scully","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1007\/s40264-022-01187-y","article-title":"Phenotype algorithms for the identification and characterization of vaccine-induced thrombotic thrombocytopenia in real World data: A multinational network cohort study","volume":"45","author":"Shoaibi","year":"2022","journal-title":"Drug Saf."},{"key":"B21","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S0140-6736(20)32661-1","article-title":"Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, south Africa, and the UK","volume":"397","author":"Voysey","year":"2021","journal-title":"Lancet"},{"volume-title":"Guidance for clinical case management of thrombosis with thrombocytopenia syndrome (TTS) following vaccination to prevent coronavirus disease (COVID-19)","year":"2021","key":"B22"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1118203\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T04:44:53Z","timestamp":1679633093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1118203\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,24]]},"references-count":22,"alternative-id":["10.3389\/fphar.2023.1118203"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1118203","relation":{},"ISSN":["1663-9812"],"issn-type":[{"type":"electronic","value":"1663-9812"}],"subject":[],"published":{"date-parts":[[2023,3,24]]},"article-number":"1118203"}}