The effects of anagrelide on human megakaryocytopoiesis

Lawrence A. Solberg, Ayalew Tefferi, Karl J. Oles, Jerzy S. Tarach, Robert M. Petitt, Lee A. Forstrom, Murray N. Silverstein

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Anagrelide, an inhibitor of platelet aggregation, decreases the number of platelets in normal subjects and in patients with myeloproliferative disorders. We describe studies aimed at discovering the general mechanism(s) by which anagrelide acts. We examined three hypotheses: (1) anagrelide shortens platelet survival, (2) anagrelide inhibits the proliferation of megakaryocytic-committed progenitor cells (CFU-M), and (3) anagrelide inhibits maturation of megakaryocytes. We observed that anagrelide did not shorten platelet survival. Proliferation of CFU-M in vivo was not affected by anagrelide, although high concentrations of anagrelide inhibited CFU-M in vitro. In-vivo and in-vitro anagrelide altered the maturation of megakaryocytes, causing a decrease in their size and changing other morphometric features. We conclude that anagrelide decreases the number of platelets primarily by interfering with the maturation of megakaryocytes.

Original languageEnglish (US)
Pages (from-to)174-180
Number of pages7
JournalBritish journal of haematology
Volume99
Issue number1
DOIs
StatePublished - Jan 1 1997

Keywords

  • Digital imaging analysis
  • Glycoprotein IIb/IIIa
  • Haemopoiesis
  • Megakaryocyte
  • Stem cells

ASJC Scopus subject areas

  • Hematology

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    Solberg, L. A., Tefferi, A., Oles, K. J., Tarach, J. S., Petitt, R. M., Forstrom, L. A., & Silverstein, M. N. (1997). The effects of anagrelide on human megakaryocytopoiesis. British journal of haematology, 99(1), 174-180. https://doi.org/10.1046/j.1365-2141.1997.3503164.x