Analytical Review: The Pathogenesis of Spherocytes and Leptocytes (Target Cells)

1. The history of knowledge regarding the spherocyte and the target cell together with the theories of their pathogenic significance are reviewed.

2. Although these abnormal erythrocytes are generally considered to represent primary abnormalities of shape, it is pointed out that the abnormalities are secondary to disproportions between the cellular volume and the surface area.

3. The spherocyte is a thick red cell because—as compared with the normal erythrocyte—its surface area encloses a relatively larger volume. The disproportion may come about by increasing the volume, which occurs in hypotonic solutions and during periods of stagnation, either in the spleen or in the test tube. The disproportion may also result from shrinkage of the cellular surface, a change which occurs when a normal red cell is injured by various "sphering agents" including antibodies or when the natural "anti-sphering factor" is removed from its surface. In hereditary spherocytosis the cellular surface area is computed to be abnormally small. This apparently occurs as the result of a developmental defect.

4. The target cell, which is a thin erythrocyte, is the antithesis of the spherocyte. Compared with the normal red cell its volume is found to be small for the surface area. The disproportion occurs if the volume is reduced as when cells are exposed to a hypertonic environment. It occurs in hypochromia, as a consequence of too little hemoglobin. Target cells also result when a normal cellular volume is enclosed in an overlarge surface. This occurs in normal persons after splenectomy where it may be due to absence of some splenic effect on the maturation of the red cell surface. In hepatic disease the large surface area is an acquired change affecting even transfused red cells. It is reversible. In sickle cell anemia the large surface is apparently an hereditary characteristic.