{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T23:57:18Z","timestamp":1776211038291,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21\u201075\u201000109"],"award-info":[{"award-number":["21\u201075\u201000109"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23\u201074\u201000057"],"award-info":[{"award-number":["23\u201074\u201000057"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Wiskott\u2013Aldrich syndrome (WAS) is an X\u2010linked recessive disorder caused by <jats:italic>WAS<\/jats:italic> gene mutations resulting in haematopoietic\/immune cell defects. Recent studies report accelerated death of WAS platelets and lymphocytes. Data on megakaryocyte (MK) maturation, viability and their possible role in thrombocytopenia development in WAS are limited. In this study we evaluate the MK viability and morphology in untreated, romiplostim\u2010treated WAS patients compared with normal controls. The study included 32 WAS patients and 17 healthy donors. MKs were captured from bone marrow aspirates by surface\u2010immobilized anti\u2010GPIIb\u2010IIIa antibody. Viability (by phosphatidylserine [PS] externalization), distribution by maturation stages and size of MK were determined by light microscopy. MK distribution by maturation stages in patients differed from controls. 40\u2009\u00b1\u200922% of WAS MKs versus 23\u2009\u00b1\u200911% of normal MKs were at maturation stage 3 (<jats:italic>p<\/jats:italic>\u2009=\u20090.02), whereas 24\u2009\u00b1\u200920% in WAS and 39\u2009\u00b1\u200914% in controls had megakaryoblast morphology (<jats:italic>p<\/jats:italic>\u2009=\u20090.05). Romiplostim treatment changed the MK maturation stages distribution close to normal. PS\u2010positive (PS+) MK in WAS was significantly higher (21\u2009\u00b1\u200921%) than in healthy controls (2\u2009\u00b1\u20094%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). WAS patients with more damaging truncating mutations and higher disease score had higher PS+ MK fraction (Spearman <jats:italic>r<\/jats:italic>\u2009=\u20090.6, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.003). We conclude that WAS MKs have increased cell death tendency and changes in maturation pattern. Both could contribute to thrombocytopenia in WAS patients.<\/jats:p>","DOI":"10.1111\/bjh.18875","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T04:25:07Z","timestamp":1684902307000},"page":"645-656","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Accelerated death of megakaryocytes from <scp>Wiskott\u2013Aldrich<\/scp> syndrome patients"],"prefix":"10.1111","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2930-8768","authenticated-orcid":false,"given":"Sergei I.","family":"Obydennyi","sequence":"first","affiliation":[{"name":"Center for Theoretical Problems of Physicochemical Pharmacology  Moscow Russia"},{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology  Moscow 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