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Although CD226 deficiency did not cause MK polyploidization or platelet granule abnormalities, increased MK counts were detected in the femora bone marrow (BM) and spleen of CD226 KO mice. Particularly, CD226 KO mice have a more extensive membrane system in MKs and platelets than wild\u2010type (WT) mice. We also demonstrated that CD226 KO mice displayed increased platelet counts, shortened bleeding time, and enhanced platelet aggregation. CD226 KO platelets had an increased mature platelet ratio compared to the control platelets. In addition, the observed reduction in bleeding time may be due to decreased nitric oxide (NO) production in the platelets. Platelet\u2010specific CD226\u2010deficient mice showed similar increased MK counts, shortened bleeding time, enhanced platelet aggregation, and decreased NO production in platelets. Furthermore, we performed middle cerebral artery occlusion\u2010reperfusion surgery on WT and CD226 KO mice to explore the potential effect of CD226 on acute ischemia\u2010reperfusion injury; the results revealed that CD226 deficiency led to significantly increased infarct area. Thus, CD226 is a promising candidate for the treatment of thrombotic disorders.<\/jats:p>","DOI":"10.1096\/fj.201902142r","type":"journal-article","created":{"date-parts":[[2020,4,5]],"date-time":"2020-04-05T05:45:41Z","timestamp":1586065541000},"page":"6871-6887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Deficiency of platelet adhesion molecule CD226 causes megakaryocyte development and platelet hyperactivity"],"prefix":"10.1096","volume":"34","author":[{"given":"Jinxue","family":"Zhang","sequence":"first","affiliation":[{"name":"Orthopedic Department of Tangdu Hospital Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Ding","sequence":"additional","affiliation":[{"name":"Orthopedic Department of Tangdu Hospital Fourth Military Medical University Xi'an 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