{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T23:56:46Z","timestamp":1776211006108,"version":"3.50.1"},"reference-count":30,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,3,1]]},"abstract":"<jats:p>To define the mechanism by which anagrelide normalizes the platelet count in essential thrombocythemia, we studied in vivo megakaryocytopoiesis in 10 newly diagnosed patients prior to and while on anagrelide therapy. Using flow cytometric analysis of aspirated marrow, megakaryocytopoiesis was quantified and correlated with the autologous platelet production rate. Megakaryocytes were identified by CD41a expression and enumerated in relation to the nucleated marrow erythroid precursors. Megakaryocyte diameters were directly measured by time-of-flight technique, and cell ploidy was measured by DNA staining. Two to 3 thousand megakaryocytes were analyzed in each sample. In the 10 patients, the platelet count was 1063\u2009\u00b1\u2009419\u2009\u00d7\u2009109platelets\/L (mean \u00b1 1 SD) with markedly increased production (237\u2009\u00b1\u200974\u2009\u00d7\u2009109 platelets\/L per day versus 43.1\u2009\u00b1\u20098.4\u2009\u00d7\u2009109 platelets\/L per day in healthy individuals). The platelet survival was 8.2\u2009\u00b1\u20091.1 days versus 9.0\u2009\u00b1\u20090.5 days in healthy controls (P\u2009&amp;gt;\u2009.05). Megakaryocyte diameter was increased to 46 \u03bcm (versus 37 \u03bcm in controls; range, 21 \u03bcm for 2N to 56 \u03bcm for 64N cells). The volume increased to 48\u2009\u00d7\u2009103 \u03bcm3 versus 26\u2009\u00d7\u2009103 \u03bcm3 in controls, and the number increased to 14\u2009\u00d7\u2009106\/kg (versus 7\u2009\u00d7\u2009106\/kg in controls), resulting in 3.7-fold increase in megakaryocyte mass (66\u2009\u00d7\u20091010 \u03bcm3\/kg versus 18\u2009\u00d7\u20091010 \u03bcm3\/kg). Cell ploidy was enhanced showing a modal ploidy of 32N (versus 16N in healthy controls) with marked increase in 64N and 128N cells (P\u2009&amp;lt;\u2009.05). Anagrelide therapy reduced the platelet counts to 361\u2009\u00b1\u200953\u2009\u00d7\u2009109 platelets\/L and the turnover rate to 81\u2009\u00d7\u2009109 platelets\/L per day. The platelet survival was unchanged. Following therapy, megakaryocyte number decreased to 8\u2009\u00d7\u2009106\/kg, diameter to 40 \u03bcm, and volume to 34\u2009\u00d7\u2009103 \u03bcm3 with a normalized modal ploidy of 16N, resulting in a megakaryocyte mass reduced by 60% (28\u2009\u00d7\u20091010 \u03bcm3\/kg;P\u2009&amp;lt;\u2009.05). This reduction in cell mass closely correlated with the reduction in platelet count and production rate by 66% (r\u2009=\u20090.96). The present data indicate that in essential thrombocythemia anagrelide therapy decreases circulating platelets by reducing both megakaryocyte hyperproliferation and differentiation.<\/jats:p>","DOI":"10.1182\/blood.v99.5.1602","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:40Z","timestamp":1027774000000},"page":"1602-1609","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":67,"title":["Effects of anagrelide on in vivo megakaryocyte proliferation and maturation in essential thrombocythemia"],"prefix":"10.1182","volume":"99","author":[{"given":"Aaron","family":"Tomer","sequence":"first","affiliation":[{"name":"From the Blood Bank and Transfusion Medicine, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021217411498600_B1","first-page":"340","article-title":"Essential (primary) thrombocythemia.","volume-title":"Hematology.","author":"Schafer","year":"1995","edition":"5th ed."},{"key":"2020021217411498600_B2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s002770050536","article-title":"Treatment of essential thrombocythemia with special emphasis on leukomogenic risk.","volume":"78","author":"Finazzi","year":"1999","journal-title":"Ann Hematol."},{"key":"2020021217411498600_B3","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1056\/NEJM198805193182002","article-title":"Anagrelide: a new drug for treating thrombocytosis.","volume":"318","author":"Silverstein","year":"1988","journal-title":"N Engl J Med."},{"key":"2020021217411498600_B4","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0002-9343(92)90017-6","article-title":"Anagrelide, a therapy for thrombocythemic states: experience in 577 patients.","volume":"92","author":"Anagrelide Study Group","year":"1992","journal-title":"Am J Med."},{"key":"2020021217411498600_B5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0268-960X(97)90001-1","article-title":"New drugs in essential thrombocythemia and polycythemia vera.","volume":"11","author":"Tefferi","year":"1997","journal-title":"Blood Rev."},{"key":"2020021217411498600_B6","first-page":"51","article-title":"Anagrelide for control of thrombocythemia in polycythemia and other myeloproliferative disorders.","volume":"34","author":"Petitt","year":"1997","journal-title":"Semin Hematol."},{"key":"2020021217411498600_B7","doi-asserted-by":"crossref","first-page":"809","DOI":"10.2165\/00003495-199447050-00007","article-title":"Anagrelide. 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