Algorithm for the evaluation of macrocytic anemia. (RBC = red blood cell; MMA = methylmalonic acid.)
Physicians should begin by ordering a peripheral smear, a reticulocyte count, and a vitamin B12 serum level for all patients with macrocytosis. It may be necessary to specifically order a reticulocyte index in some laboratories, which assesses if there is an adequate bone marrow response. Hemorrhage or hemolysis is the most likely cause if the reticulocyte count is elevated, but anemia recovery also causes an elevation in the reticulocyte count. Measures of vitamin B12 are a useful part of the initial work-up, because if vitamin B12 deficiency is present but undiagnosed, folate repletion will correct the megaloblastic anemia, but not the possible neuropathic changes that occur with B12 deficiency.
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