University of Virginia Health System

Macrocyte

Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

Description:

A red cell that is larger than a normal red cell. On any given blood smear, the size of a normal red cell is approximately that of the nucleus of a very small lymphocyte. Depending on the percentage of macrocytes present, the MCV may be elevated. If the RDW is increased (due to anisocytosis), the MCV may not reflect the degree of macrocytosis.

Pathobiology:

Results from several different mechanisms:
    -Megaloblastic erythropoiesis, e.g. Vitamin B-12 and folate deficiency
    -Dyserythropoiesis, e.g. myelodysplastic syndromes
    -Altered lipid content of the red cell membrane, e.g. liver disease
    -In some cases the exact mechanism is unclear, e.g. aplastic anemia

Differential Diagnosis:

• Vitamin B-12 deficiency
  • Macro-ovalocytes are more characteristic, and if associated with hypersegmented granulocytes and a variable degree of anisopoikilocytosis in the absence of other causes (e.g. drugs), is essentially diagnostic of either Vitamin B-12 or folate deficiency.
    • Pernicious anemia (autoimmune disorder)
    • Gastrectomy
    • Terminal ileal resection or disease (Crohn's disease, tropical sprue) 
    • Fish tapeworm infestation (Diphyllobothrium latum)
    • Nutritional (rare)- only seen in strict vegans
    • Hereditary defects, e.g. transcoboliamin II deficiency, intrinsic factor deficiency
• Folate deficiency
  • Nutritional (decreased intake), e.g. malnourished individuals, alcoholics
  • Decreased absorption, e.g. sprue and other malabsorptive disorders of the small intestines. 
  • Increased requirement, e.g. pregnancy, chronic hemolytic anemias
  • Hereditary defects, e.g. congenital folate malabsorption, dihydrofolate reductase deficiency
• Drugs
  • Anti-folate drugs, e.g. methotrexate, trimethoprin, metformin (interferes with absorption of folate and vitamin B-12)
  • Other drugs, e.g. phenytoin (Dilantin), imatinib (Gleevec)
• Liver disease- macrotarget cells are more characteristic. Another macrocyte seen in liver disease is the thin macrocyte (leptocyte, wafer cell), characterized by an increased area of central palor. Acanthocytes are also characteristic findings. 
• Alcohol (amount of consumption required varies with the individual)
  • Increased stomatocytes are more characteristic and patients usually are not anemic.
• Myelodysplastic syndromes- probably the most common cause of macrocytosis in older people. A variable degree of anisopoikilocytosis is frequently seen together with evidence of dysplasia of other hematopoietic lineages, e.g. hypogranulated and hypolobated neutrophils.
• Aplastic and hypoplastic anemia
• Congenital dyserythropoietic anemias
• Diamond-Blackfan anemia 
• Other hereditary disorders, e.g. orotic aciduria, thiamine-responsive megaloblastic anemia
• Hypothroidism
• Pregnancy
• Neonates
• Chronic lung disease and heavy cigarette smoking
• Reticulocytes- the macrocyte is polychromatophilic (reticulocyte)
• Pseudomacrocytosis- Elevated MCV on automated counters without macrocytosis, e.g. hemagglutination, rouleaux formation

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