|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 10 (May 15), 1999:
pp. 3286-3293
The Effect of Recombinant Human Erythropoietin on Platelet Counts Is
Strongly Modulated by the Adequacy of Iron Supply
Martine Loo and
Yves Beguin
From the Department of Medicine, Division of Hematology, University
of Liège, Liège, Belgium.
The effect of recombinant human erythropoietin (rHuEpo) on
megakaryopoiesis remains controversial. Treatment with rHuEpo in renal
failure patients has been associated with a slight elevation of
platelet counts. In animal studies, high doses of rHuEpo produced an
increase of platelet counts followed by a gradual return to normal
after 7 to 15 days or even a substantial degree of thrombocytopenia. However, because iron deficiency is also known to be associated with
thrombocytosis, (functional) iron deficiency during rHuEpo could be
contributing to these observations. We investigated the impact of iron
supply on changes in platelet counts induced by rHuEpo. Rats were
either fed normal food (normal rats) or received 1% carbonyl iron for
2 weeks or 3 months, as well as during the experiment, to achieve iron
supplementation or overload, respectively. Rats of all three categories
then received daily intravenous injections of rHuEpo (10, 50, or 150 U)
or normal saline (0 U) for 20 days. With 0 to 10 U rHuEpo, platelets
remained stable. In normal rats receiving 50 to 150 U rHuEpo, platelets
increased to 120% to 140% of baseline at 4 to 12 days to level off at
120% at 16 to 20 days. This response was less sustained in
splenectomized animals. Iron-supplemented rats receiving 50 to 150 U
rHuEpo also increased platelets initially, but the peak was at day 4, followed by a gradual return to baseline and even a moderate
thrombocytopenia later on. Iron-overloaded rats receiving 50 to 150 U
rHuEpo also had increased platelets at day 4, but the duration of
platelet increase was shorter, and they experienced a more pronounced
degree of thrombocytopenia in proportion to the dose of rHuEpo. Because
the early elevation of platelets was of larger magnitude than
hematocrit changes, it is unlikely that it could be
accounted for by shrinkage of plasma volume. Because it was observed in
all three iron conditions, there appears to be some direct positive
effect of rHuEpo on platelet production. However, after this transient
effect, expanded erythropoiesis appears to exert a negative impact upon
platelet production. Secondary thrombocytopenia was not related to
splenic pooling, and its very slow correction after cessation of rHuEpo
therapy is not compatible with changes in platelet survival. Rather, it
is consistent with stem cell competition between erythroid and
megakaryocytic development. However, this secondary thrombocytopenia is
masked by (functional) iron deficiency in rats not receiving an
adequate iron supply from food or stores.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Piron, M. Loo, A. Gothot, F. Tassin, G. Fillet, and Y. Beguin
Cessation of intensive treatment with recombinant human erythropoietin is followed by secondary anemia
Blood,
January 15, 2001;
97(2):
442 - 448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Go, L. F. Porrata, and T. G. Call
Thrombocytopenia after Iron Dextran Administration in a Patient with Severe Iron Deficiency Anemia
Ann Intern Med,
June 6, 2000;
132(11):
925 - 925.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Stohlawetz, L. Dzirlo, N. Hergovich, E. Lackner, C. Mensik, H. G. Eichler, E. Kabrna, K. Geissler, and B. Jilma
Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans
Blood,
May 1, 2000;
95(9):
2983 - 2989.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
