{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:13:30Z","timestamp":1790133210895,"version":"4.0.1"},"reference-count":49,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,7,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Vitamin K antagonists (VKAs) have been used in 1% of the world\u2019s population for prophylaxis or treatment of thromboembolic events for 64 years. Impairment of osteoblast function and osteoporosis has been described in patients receiving VKAs. Given the involvement of cells of the bone marrow microenvironment (BMM), such as mesenchymal stem cells (MSCs) and macrophages, as well as other factors such as the extracellular matrix for the maintenance of normal hematopoietic stem cells (HSCs), we investigated a possible effect of VKAs on hematopoiesis via the BMM. Using various transplantation and in vitro assays, we show here that VKAs alter parameters of bone physiology and reduce functional HSCs 8-fold. We implicate impairment of the functional, secreted, vitamin K-dependent, \u03b3-carboxylated form of periostin by macrophages and, to a lesser extent, MSCs of the BMM and integrin \u03b23-AKT signaling in HSCs as at least partly causative of this effect, with VKAs not being directly toxic to HSCs. In patients, VKA use associates with modestly reduced leukocyte and monocyte counts, albeit within the normal reference range. VKAs decrease human HSC engraftment in immunosuppressed mice. Following published examples that alteration of the BMM can lead to hematological malignancies in mice, we describe, without providing a causal link, that the odds of VKA use are higher in patients with vs without a diagnosis of myelodysplastic syndrome (MDS). These results demonstrate that VKA treatment impairs HSC function via impairment of the BMM and the periostin\/integrin \u03b23 axis, possibly associating with increased MDS risk.<\/jats:p>","DOI":"10.1182\/blood.2018874214","type":"journal-article","created":{"date-parts":[[2019,4,19]],"date-time":"2019-04-19T19:06:06Z","timestamp":1555700766000},"page":"227-238","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":26,"title":["Vitamin K antagonism impairs the bone marrow microenvironment and hematopoiesis"],"prefix":"10.1182","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2214-9450","authenticated-orcid":false,"given":"Divij","family":"Verma","sequence":"first","affiliation":[{"name":"Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, 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