The effect of high doses of recombinant human erythropoietin on megakaryocytopoiesis and platelet production in splenectomized mice

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Abstract
The effects of recombinant human erythropoietin (rHuEpo) on megakaryocytopoiesis and platelet production were investigated in splenectomized, sham-operated and intact mice. When splenectomized mice were injected with 50 U of rHuEpo daily for 4 d, peripheral platelet counts, megakaryocyte (MK) size and the percentage of mature MK (stage IV MK) increased from 1 to 4 d after the initial rHuEpo injection. The total number of marrow MK colony forming units (CFU-MK) increased from 2 to 4 d after the initial injection. Furthermore, from days 6 to 8, the total number of marrow MK also increased. In addition, when the dose of rHuEpo was increased to 20 .apprx. 200 U per mouse, clear dose responses were detected in platelet counts and MK numbers. When sham-operated and intact mice were injected with rHuEpo, no significant change in platelet numbers was detected. The number of MK, MK size and the number of CFU-MK increased only in spleen, not in bone marrow. Our data indicate that Epo has stimulatory effects on platelet production in vivo, if used in sufficient quantities.