Neutrophils, hypersegmented

Figure 28-1. Characteristic features of vitamin B12 or folate deficiency in the peripheral blood include larger-than-normal mature red blood cells (oval macrocytes with an elevated mean corpuscular volume) and large hypersegmented neutrophils (1 neutrophil with six nuclear lobes or more than 5% neutrophils with five nuclear lobes).These characteristics are associated with megaloblastic changes in the bone marrow and are the result of fewer cell divisions due to impaired DNA synthesis.

Deficiency of either folic acid or vitamin B12 restdts in megaloblastic anemia -the release into circulation of immature erythrocytes because of failure of the normal process of maturation in the bone marrow (Wickramasinghe, 1995, 1999). There may also be low white cell and platelet counts, as well as increased numbers of hypersegmented neutrophils. Iron deficiency may mask the megaloblastic anemia. 

The hematological signs of folate deficiency manifest first in the neutrophils and then in red blood cells. Normally, close to half of the neutrophils contain three lobes 20 to 40% have two lobes and 15 to 25% have four lobes. In folate deficiency, segmentation of the neutrophils increases cells with 6 to 10 lobes may be detected. The detection of three five-lobed neutrophils in a count of 100 neutrophils indicates the possibility of folate deficiency. Diagrams of normal and hypersegmented neutrophils are shown in Figure 9.20. 

In 1962, a physician (H14) placed himself on a diet which, when assayed, was found to provide only 5 pg of folate daily. Up to that time no diet had been devised that contained so little folate, and it was made possible only by boiling each 100 g portion of all those constituents that contained more than a trace of the vitamin for 10 minutes in two liters of water. Tlie water was then discarded and the procedure repeated twice (H15). On this diet early megaloblastic change was noted after 137 days. The serum level of the vitamin fell after 14 days followed by the appearance of hypersegmented neutrophils. Formiminoglutamic acid then appeared in the urine and shortly before the megaloblastic change occurred the red cell folate fell. This experiment provided important information on body stores and the sequence of events in folate deficiency. While the diet was not completely free of folate, its content had been carefully measured and was very small. It was calcu-... 

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