Macrocytic Anemia

Overview
  • Macrocytic Anemias, also known as Megaloblastic Anemias, refer to a categorization of anemias defined as those which yield larger-than-normal erythrocytes, typically with a Mean Corpuscular Volume (MCV) greater than 100. The common theme of etiologies that give rise to macrocytic anemias are their capacity to interfere with DNA Synthesis. This results in ineffective erythropoiesis within the bone marrow and over time, anemia. Consistent with this, the two basic categories of etiological causes include: 1) Deficiencies of vitamins critical for DNA synthesis, and 2) Drugs that interfere with nucleotide synthesis
Etiologies
  • Vitamin Deficiencies: Vitamin B12 and folate are critical for synthesis of nucleotides and consequently their deficiency is a common cause of megaloblastic anemia. Please refer to the Vitamin B12 deficiency and folate deficiency pages for an in-depth discussion of the causes, diagnosis, and clinical consequences, beyond that of macrocytic anemia, for these conditions.
  • Drugs: A variety of drugs can interfere with nucleotide synthesis and thus yield megaloblastic anemia. They do so either by interfering with folate biosynthesis (methotrexate, bacterial metabolism inhibitors) or directly interfering with the mammalian DNA synthetic enzymes (zidovudine).
Important Caveat
  • It is critical to point out at this juncture that the automated machinery used for obtaining complete blood counts (CBCs) can often mistake newly generated reticulocytes as larger-than-normal erythrocytes. Consequently, in patients with very high reticulocyte indices, such as those suffering from acute hemorrhage or hemolysis, the CBC may mistakenly suggest that the patient's erythrocytes are macrocytic when in fact there are a large percentage of reticulocytes in the peripheral blood. Therefore, a high clinical suspicion should be employed in the right context when a macrocytosis is identified