Reticulocyte Size in Nutritional

Alterations in reticulocyte size occur 2-3 days after the onset of iron deficient or megaloblastic erythropoiesis and precede, by several weeks, changes in mean corpuscular volume (MCV). Iron-deficiency anemia induced in a normal subject by repeated phlebotomies was characterized by the initial development of larger than normal reticulocytes followed by an abrupt decrease in reticulocyte size. Microreticulocytes appeared 3 days after the fall in per cent iron saturation and antedated the decrease in MCV to below normal by 6 wk. Mean reticulocyte size was disproportionately smaller than normal in patients presenting with iron deficiency. In contrast, reticulocyte size increased abruptly in a patient (and rats) 2-3 days after administration of methotrexate. Mean reticulocyte size was disproportionately larger than normal in patients presenting with folate or vitamin B,2 deficiency. Specific replacement therapy with iron, folate, or vitamin B,2 was quickly followed by normalization of reticulocyte size. T HE MEASUREMENT of mean corpuscular volume (MCV) is often unsatisfactory for the evaluation of patients with anemia secondary to early iron, folate, or vitamin B12 deficiency. The MCV may not be useful because the long survival of red cells allows the indices to remain in the normal range for 6-12 wk following the development of iron deficiency, as shown by the classic phlebotomy study of Conrad and Crosby.’ Likewise, the folate deprivation study of Herbert2 demonstrates that macrocytosis does not develop until 14 wk following the attainment of low serum folate levels. The purpose of our study was to test the hypothesis that changes in reticulocyte size would precede changes in MCV in patients developing iron, folate, or B,2 deficiency. Accordingly, mean reticulocyte size was determined in normals, in a normal subject undergoing repetitive phlebotomies, and in patients with iron, folate, and B,2 deficiencies. Selected patients were restudied after specific replacement therapy. Serial changes in the reticulocyte size of a patient with metastatic adenocarcinoma receiving high dose methotrexate with leucovorin factor rescue therapy were observed. Similar observations were also made in rats given methotrexate.