Nine comparable patients with vitamin B12 deficiency were studied during therapy by iron kinetic technic with special attention to the earliest phase of reticulocyte response, in order to define the fate of a megaloblast population and to explain the very high reticulocytosis typical of the pernicious anemia response.

After B12 therapy, there is a 2-2.5 day lag before reticulocytosis, during which ineffective erythropoiesis of the megaloblasts continues and repopulation by an entirely new normoblast series from the stem cell level occurs. Once reticulocytosis begins, it is characterized by delivery of very young reticulocytes from the bone marrow. These cells demonstrate a prolonged maturation phase, resulting in cumulative counting over several days and an apparent greater than expected reticulocyte level. If the reticulocyte peak is corrected for this maturation delay, a reticulocyte production index is obtained which correlates well with the measured plasma iron turnover production indices.

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