Macrocytosis Resulting from Early Denucleation of Erythroid Precursors

In an attempt to elucidate the mechanism of production of macrocytosis in acute anemia, we studied changes in red cell volume and hemoglobin content, the RNA level of normoblasts and reticulocytes and RNA synthesis in reticulocytes of rabbits made anemic by blood loss or phenylhydrazine administration. The results were as follows:

(1) In severe phenylhydrazine anemia, red cell volume and hemoglobin content per cell increased to twice the normal values.

(2) The RNA level of normoblasts decreases with the maturation of the cells and reaches a minimum at the orthochromatic stage. The decrease is similar in the normal and anemic rabbits.

(3) The RNA level of reticulocytes in the bone marrow is higher in anemic than in normal rabbits. In general, the RNA level of reticulocytes of anemic rabbits is comparable to that of the polychromatic normoblasts, while in normal rabbits this value is comparable to that of orthochromatic normoblasts.

(4) Autoradiographs of reticulocytes incubated with H³-uridine indicate that the increased level of reticulocyte RNA of anemic rabbits is not due to newly synthesized RNA.

From these results, we conclude that in an "emergency" situation of erythropoietic stimulation denucleation of normoblasts occurs at the polychromatic stage of red cell maturation, with skipping of the terminal cell division to orthochromatic cells and formation of macrocytic reticulocytes and red cells.