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Large, chronic doses of erythropoietin cause thrombocytopenia in mice [see
comments]
TP McDonald, RE Clift and MB Cottrell
Department of Animal Science, College of Veterinary Medicine, University of
Tennessee, Knoxville 37901-1071.
Both large, acute doses of erythropoietin (EPO) and short-term hypoxia
increase platelet counts in mice, but long-term hypoxia causes
thrombocytopenia. Therefore, we tested the hypothesis that EPO injected in
large, chronic doses (a total of 80 U of EPO over a 7-day period) might
cause thrombocytopenia. EPO caused increased red blood cell (RBC)
production, ie, increased hematocrits, RBC counts, mean cell volume (MCV),
and reticulocyte counts (from P less than .05 to P less than .0005), and
decreased thrombocytopoiesis, ie, decreased platelet counts, percent 35S
incorporation into platelets, and total circulating platelet counts (TCPC)
(P less than .0005). Femoral marrow megakaryocyte size was unchanged, but
megakaryocyte number was significantly (P less than .005) reduced in mice
treated with EPO. EPO- injected mice had increased spleen volumes (P less
than .0005), but blood volumes (BV) were unchanged. In EPO-treated,
splenectomized mice, RBC production was also increased (P less than .05 to
P less than .0005) and platelet counts, TCPC, and percent 35S incorporation
into platelets were decreased (P less than .05), but BV was not altered.
Therefore, the decrease in platelet counts observed in EPO-treated mice was
not due to increased BV or to an enlarged spleen. In other experiments,
mice were rendered acutely thrombocytopenic to increase thrombocytopoiesis,
and platelet and RBC production rates were determined. In mice with
elevated thrombocytopoiesis, RBC counts, hematocrits, percent 59Fe RBC
incorporation values, and MCV were decreased (P less than .05 to P less
than .0005). Because 59Fe RBC incorporation and MCV were not elevated, the
decrease in RBC counts and hematocrits does not appear to be due to
bleeding. Therefore, we show that large, chronic doses of EPO increase
erythropoiesis and decrease thrombocytopoiesis. Conversely, acute
thrombocytopenia causes increased thrombocytopoiesis and decreased
erythropoiesis. These findings support the hypothesis of competition
between precursor cells of the erythrocytic and megakaryocytic cell lines
(stem-cell competition) as the cause of thrombocytopenia in EPO-treated
mice and the cause of anemia in mice whose platelet production rates were
increased.
Volume 80,
Issue 2,
pp. 352-358,
07/15/1992
Copyright © 1992 by The American Society of Hematology
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