{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:26:54Z","timestamp":1783618014349,"version":"3.55.0"},"reference-count":28,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T00:00:00Z","timestamp":1572480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"publisher","award":["OTKA K16 120725"],"award-info":[{"award-number":["OTKA K16 120725"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010024","name":"Hungarian Science Foundation","doi-asserted-by":"publisher","award":["GINOP-2.3.2-15-2016-00043"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00043"]}],"id":[{"id":"10.13039\/501100010024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tyrosine kinase inhibitors (TKI) such as the BCR-ABL inhibitor dasatinib and nilotinib are highly effective therapies for chronic myeloid leukemia (CML). However, several lines of evidence suggest that dasatinib can induce bleeding which may be due to impaired collagen-induced platelet adhesion, aggregation, and secretion. Sarcoma family kinases (SFK) play central role in the GPVI-induced signaling pathway. We aimed to investigate whether and how dasatinib can modulate SFK-mediated platelet procoagulant activity in a purified system and in dasatinib\/nilotinib treated CML patients. In platelet rich plasmas of healthy volunteers, dasatinib dose-dependently reduced convulxin-induced phosphatidylserine exposure and attenuated thrombin formation. Similarly to these changes, integrin activation and clot retraction were also significantly inhibited by 100 nM dasatinib. Platelets isolated from dasatinib treated patients showed a significantly lower phosphatidylserine expression upon convulxin activation compared to premedication levels. In these samples, thrombin generation was significantly slower, and the quantity of formed thrombin was less compared to the trough sample. Western blot analyses showed decreased phosphorylation levels of the C-terminal tail and the activation loop of SFKs upon dasatinib administration. Taken together, these results suggest that dasatinib inhibits the formation of procoagulant platelets via the GPVI receptor by inhibiting phosphorylation of SFKs.<\/jats:p>","DOI":"10.3390\/ijms20215430","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T06:33:29Z","timestamp":1572503609000},"page":"5430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Dasatinib Inhibits Procoagulant and Clot Retracting Activities of Human Platelets"],"prefix":"10.3390","volume":"20","author":[{"given":"Ildik\u00f3","family":"Beke Debreceni","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, K\u00e1lm\u00e1n Laki Doctoral School, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Mezei","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Bat\u00e1r","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1rp\u00e1d","family":"Ill\u00e9s","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Kappelmayer","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, K\u00e1lm\u00e1n Laki Doctoral School, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1182\/blood-2016-01-694265","article-title":"Moving treatment-free remission into mainstream clinical practice in CML","volume":"128","author":"Hughes","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Garcia-Gutierrez, V., and Hernandez-Boluda, J.C. 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