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Refractory thrombocytopenia without significant coagulation abnormalities has also been reported after envenomation by some viperid snakes; however, the mechanisms are not well understood and therapeutic strategies are lacking. Here, we found that patients injured by Daboia siamensis or Agkistrodon halys snakes, who were resistant to standard antivenom treatment, had developed coagulopathy-independent thrombocytopenia. Venoms from these viperid snakes, rather than from the elapid snake (Bungarus multicinctus), induced platelet surface expression of neuraminidase-1 (NEU-1), and significantly increased the desialylation of the glycoproteins on human platelets. The desialylated platelets caused by viperid snake venoms were further internalized by macrophages, which resulted in reduced platelet numbers in peripheral blood. Importantly, neuraminidase inhibitor significantly decreased viper venom-induced platelet desialylation, therefore inhibiting platelet phagocytosis by macrophages, and alleviating venom-induced thrombocytopenia. Collectively, these findings support an important role for desialylated platelet clearance in the progression of viper envenomation-induced, coagulopathy-independent thrombocytopenia. Our study demonstrates that the neuraminidase inhibitor may be a potential therapy or adjuvant therapy to treat snakebite-induced thrombocytopenia.<\/jats:p>","DOI":"10.3390\/molecules27227779","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T04:24:10Z","timestamp":1668399850000},"page":"7779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in Daboia siamensis and Agkistrodon halys Envenomation-Induced Thrombocytopenia"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4225-3618","authenticated-orcid":false,"given":"Cheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China"},{"name":"Department of Laboratory Medicine, LKSKI-Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, University of Toronto, Toronto, ON M5B 1W8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enyu","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3336-4201","authenticated-orcid":false,"given":"Yunlong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9361-7688","authenticated-orcid":false,"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8651-9329","authenticated-orcid":false,"given":"Fangfang","family":"Xu","sequence":"additional","affiliation":[{"name":"The Second Clinical School of Medicine Medicial College, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiye","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7144-2891","authenticated-orcid":false,"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4320-9181","authenticated-orcid":false,"given":"Xianzhang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17063","DOI":"10.1038\/nrdp.2017.63","article-title":"Snakebite envenoming","volume":"3","author":"Gutierrez","year":"2017","journal-title":"Nat. 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