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Recombinant human erythropoietin (rHuEpo) was tested for its ability to stimulate rat megakaryopoiesis in vivo. Groups of Sprague-Dawley rats were injected with rHuEpo at a daily dose of 20, 80, or 200 U for 5 days. Significant thrombocytosis (a 30 to 40% increase over the control level) was found only in the rats that received 200 U/day, but some changes in the megakaryopoietic parameters were observed not only in the rats given 200 U/day, but also in those receiving 80 or 20 U/day. rHuEpo induced a dose-dependent elevation of megakaryocyte ploidy, with the maximum 45% increase in the mean ploidy over the control level seen in rats given 200 U/day. The size of the marrow megakaryocytes also increased dose-dependently. rHuEpo did not increase bone marrow megakaryocyte numbers, but it increased those in the spleen in a dose-dependent manner. A change of these parameters was seen as early as day 1 at 24 h after initiating the Epo injections at a time when significant thrombocytosis was already present. Moreover, a significant increase in the ratio of small acetylcholinesterase-positive bone marrow cells was also found, with the greatest response noted on day 1. Administration of a large dose of iron did not alter the thrombopoietic effect of rHuEpo. These results suggest that the in vivo administration of rHuEpo stimulates the maturation of mature as well as immature megakaryocytes already present in the bone marrow.

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