Macrocytic anemia classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Macrocytosis is the enlargement of red blood cells with near-constant haemoglobin concentration, and is defined by a mean corpuscular volume (MCV) of greater than 100 femtolitres (the precise criterion varies between laboratories).

Classification

Megaloblastic anemias (DNA replication disorders)

• Commonest cause of macrocytic anemia.
• In megaloblastic anemias cells are larger because they cannot produce DNA quickly enough to divide at the right time as they grow, and thus grow too large before division.
• Causes for the DNA synthetic problem range from lack of certain vitamins needed to produce DNA (notably folate and B12), to poisons or inhibitors of DNA replication, such as some kinds of antiviral drugs and chemotherapeutic agents.
• The pathognomonic findings of megaloblastic anemia are: megaloblasts in bone marrow, ovalocytes in the (peripheral) blood smear, and hypersegmented neutrophils.

Non megaloblastic macrocytic anemias

• Non megaloblastic macrocytic anemias, are disorders associated with increased red cell membrane surface area
• It is commonly associated with pathologies of the liver and spleen which produce codocytes or "target cells" which have a central collection of hemoglobin surrounded by a pallor (a thin area) then followed by a thicker collection of hemoglobin at the rim of the cell.

Alcohol

• Round macrocytes which are not codocytes are produced in chronic alcoholism (which produces a mild macrocytosis even in the absence of vitamin deficiency), apparently as a direct toxic effect of alcohol specifically on the bone marrow.

Association with rapid red cell turnover and reticulocytosis

Mild macrocytocis is a common finding associated with rapid blood restoration or production, since in general, "fresh" or newly-produced red cells (reticulocytes) are larger than the mean (average) size, due to slow shrinkage of normal cells over a normal red cell circulating lifetime. Thus, chronic obstructive pulmonary disease (COPD), in which which red cells are rapidly produced in response to low oxygen levels in the blood, often produces mild macrocytosis. Also, rapid blood replacement from the marrow after a traumatic blood loss, or rapid red blood cell turnover from rapid hemolysis, also often produces mild macrocytosis in the associated anemia.

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