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It is characterized by a strong systemic inflammatory response, where multiple components of the immune system are involved. Currently, there is no treatment for sepsis. Blood platelets are known for their role in haemostasis, but they also participate in inflammation through cell\u2013cell interaction and the secretion of inflammatory mediators. Interestingly, an increase in platelet activation, secretion, and aggregation with other immune cells (such as monocytes, T\u2010lymphocytes and neutrophils) has been detected in septic patients. Therefore, antiplatelet therapy in terms of P2Y<jats:sub>12<\/jats:sub> antagonists has been evaluated as a possible treatment for sepis. It was found that blocking P2Y<jats:sub>12<\/jats:sub> receptors decreased platelet marker expression and limited attachment to immune cells in some studies, but not in others. This review addresses the role of platelets in sepsis and discusses whether antagonizing P2Y<jats:sub>12<\/jats:sub> signalling pathways can alter the disease outcome. Challenges in studying P2Y<jats:sub>12<\/jats:sub> antagonists in sepsis also are discussed.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue on Platelet purinergic receptor and non\u2010thrombotic disease. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v181.4\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v181.4\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16207","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T07:54:43Z","timestamp":1690876483000},"page":"532-546","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Platelet P2Y<sub>12<\/sub> signalling pathway in the dysregulated immune response during sepsis"],"prefix":"10.1111","volume":"181","author":[{"given":"Emmanuel Boadi","family":"Amoafo","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions North Dakota State University  Fargo North Dakota 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