|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 March 2002, Vol. 99, No. 5, pp. 1602-1609
HEMATOPOIESIS
Effects of anagrelide on in vivo megakaryocyte
proliferation and maturation in essential thrombocythemia
Aaron Tomer
From the Blood Bank and Transfusion Medicine, Soroka
University Medical Center, Faculty of Health Sciences, Ben-Gurion
University of the Negev, Beer-Sheva, Israel.
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 ± 419 × 109
platelets/L (mean ± 1 SD) with markedly increased
production (237 ± 74 × 109 platelets/L per day versus
43.1 ± 8.4 × 109 platelets/L per day in healthy
individuals). The platelet survival was 8.2 ± 1.1 days versus
9.0 ± 0.5 days in healthy controls (P > .05).
Megakaryocyte diameter was increased to 46 µm (versus 37 µm in
controls; range, 21 µm for 2N to 56 µm for 64N cells). The
volume increased to 48 × 103 µm3 versus
26 × 103 µm3 in controls, and the number
increased to 14 × 106/kg (versus
7 × 106/kg in controls), resulting in 3.7-fold increase
in megakaryocyte mass (66 × 1010 µm3/kg
versus 18 × 1010 µm3/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 < .05). Anagrelide therapy reduced the platelet
counts to 361 ± 53 × 109 platelets/L and the turnover
rate to 81 × 109 platelets/L per day. The platelet
survival was unchanged. Following therapy, megakaryocyte number
decreased to 8 × 106/kg, diameter to 40 µm, and volume
to 34 × 103 µm3 with a normalized modal
ploidy of 16N, resulting in a megakaryocyte mass reduced by 60%
(28 × 1010 µm3/kg;
P < .05). This reduction in cell mass closely correlated with the reduction in platelet count and production rate by 66% (r = 0.96). The present data indicate that in essential
thrombocythemia anagrelide therapy decreases circulating platelets by
reducing both megakaryocyte hyperproliferation and differentiation.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K. Freson, K. Peeters, R. De Vos, C. Wittevrongel, C. Thys, M. F. Hoylaerts, J. Vermylen, and C. Van Geet
PACAP and its receptor VPAC1 regulate megakaryocyte maturation: therapeutic implications
Blood,
February 15, 2008;
111(4):
1885 - 1893.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Schafer
Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia
Blood,
June 1, 2006;
107(11):
4214 - 4222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. N. Harrison, P. J. Campbell, G. Buck, K. Wheatley, C. L. East, D. Bareford, B. S. Wilkins, J. D. van der Walt, J. T. Reilly, A. P. Grigg, et al.
Hydroxyurea Compared with Anagrelide in High-Risk Essential Thrombocythemia
N. Engl. J. Med.,
July 7, 2005;
353(1):
33 - 45.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. E. J. Rodwell, M. L. Troxell, and R. A. Lafayette
Renal tubular injury associated with anagrelide use
Nephrol. Dial. Transplant.,
May 1, 2005;
20(5):
988 - 990.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tomer
Human marrow megakaryocyte differentiation: multiparameter correlative analysis identifies von Willebrand factor as a sensitive and distinctive marker for early (2N and 4N) megakaryocytes
Blood,
November 1, 2004;
104(9):
2722 - 2727.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Schafer
Thrombocytosis
N. Engl. J. Med.,
March 18, 2004;
350(12):
1211 - 1219.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. McMillan, L. Wang, A. Tomer, J. Nichol, and J. Pistillo
Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP
Blood,
February 15, 2004;
103(4):
1364 - 1369.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Spivak, G. Barosi, G. Tognoni, T. Barbui, G. Finazzi, R. Marchioli, and M. Marchetti
Chronic Myeloproliferative Disorders
Hematology,
January 1, 2003;
2003(1):
200 - 224.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
