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A hypersegmented neutrophil is a clinical laboratory finding. It is visualized by drawing blood from a patient and viewing the blood smeared on a slide under a microscope. Normally, the number of segments in the nucleus of a neutrophil increases as it matures and ages after the neutrophil is released into the blood from the bone marrow. Although normal neutrophils only contain three or four nuclear lobes (the "segments"), hypersegmented neutrophils contain six or more lobes.
Hypersegmented neutrophils have classically been thought to be pathognomonic of the class of anemias called megaloblastic anemias (anemias caused by failure of bone marrow blood-forming cells to make DNA, often caused by vitamin B12 or folate deficiencies, or DNA-replication poisons). However, in seeming contradiction to this, several studies have strongly associated neutrophil hypersegmentation with iron deficiency anemia. In one study 81% of children with iron deficiency had hypersegmented neutrophils, vs. 9% of controls. The mechanism for hypersegmentation in iron deficiency is not yet clear, but has been suggested to be concurrent iron and vitamin deficiency.
One of the earliest, notable changes in the peripheral blood in megaloblastic processes is the appearance of hypersegmented neutrophils. Because of the short life-span of neutrophils, these abnormal hypersegmented neutrophils characteristically appear even before the onset of anemia in megaloblastic processes. Such neutrophils are less often seen in the other classes of anemia, which together are far more common than megaloblastic types of anemia. However, as noted, the use of hypersegmented neutrophils to diagnose type of anemia is limited by the fact that different types of nutrient deficiency anemia may coexist.
Note that pernicious anemia is a type of megaloblastic anemia, and as such, is expected to show hypersegmented neutrophils.