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

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 20-200 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.