The effects of anagrelide on human megakaryocytopoiesis

• Published in: British journal of haematology Vol. 99; no. 1; pp. 174 - 180
• Main Authors: Solberg Jr, Lawrence A., Tefferi, Ayalew, Oles, Karl J., Tarach, Jerzy S., Petitt, Robert M., Forstrom, Lee A., Silverstein, Murray N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-10-1997; Blackwell
• Subjects: Adult; Biological and medical sciences; Blood Platelets - cytology; Blood Platelets - drug effects; Blood. Blood coagulation. Reticuloendothelial system; Cell Division; Cell Survival; Cells, Cultured; Cellular Senescence - drug effects; digital imaging analysis; Female; glycoprotein IIb/IIIa; haemopoiesis; Humans; Male; Medical sciences; megakaryocyte; Megakaryocytes - cytology; Megakaryocytes - drug effects; Middle Aged; Pharmacology. Drug treatments; Platelet Aggregation Inhibitors - pharmacology; Quinazolines - pharmacology; Stem Cells; Human; Megakaryocytopoiesis; Hematopoiesis; Stem cell; Hematopoietic cell; Megakaryocyte; Digital image; Cell differentiation; Mechanism of action; Antiplatelet agent; Anagrelide
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.1997.3503164.x

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.