The Target Cell: An Overview

Joseph Boutureira, DVM; Kenneth S. Latimer, DVM, PHD; Perry J. Bain, DVM, PhD; Paula M. Krimer, DVM, DVSc

Class of 2003, Ross University, School of Veterinary Medicine, St. Kitts, West Indies (Boutureira) and Department of Pathology (Latimer, Bain, Krimer), College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7388

General Characteristics of Erythrocytes

Erythrocytes, or red blood cells, are the most numerous circulating blood cell in any species. In humans and most mammals, erythrocytes are anucleate and generally have the shape of a biconcave lens. An exception is the presence of oval to ellipsoidal erthyrocytes in members of the Camellidae family (e.g., llama, alpaca). Nonmammalian vertebrates, such as fish, amphibians, reptiles and birds, also may have oval to ellipsoidal erythrocytes and the nucleus is retained.¹

Red blood cells are rich in hemoglobin, a protein that binds and transports oxygen. Hemoglobin is a tetramer composed of four heme groups, each of which is attached to a globin chain. The heme moiety consists of a tetrapyrrole ring containing an iron atom in the ferrous (Fe²⁺) state. The globin chains are present in identical pairs that are designated as alpha chains and beta chains. Erythrocytes also partially recover carbon dioxide produced as waste product of cellular respiration. The biconcave shape of these cells increases the surface area to cytoplasmic volume ratio. These characteristics increase the efficiency of oxygen diffusion. The biconcave disk also allows erythrocyte flexibility and deformability so erythrocytes can traverse the microvasculature.

Various Alterations in the Shape of Erythrocytes

A variety of morphologic changes have been observed in erythrocytes by examination of Romanowsky-stained blood smears and by examination of cells prepared for scanning electron microscopy. An abbreviated list of common changes in the shape of erythrocytes are listed in Table 1.

Table 1. Changes in erythrocyte morphology associated with various medical disorders.

Target Cell (Codocyte)

Target cells, also known as codocytes, have the appearance of a target with a bullseye (Figs. 1 & 2). Such cells are thin and have a disproportional increase in the surface membrane area to volume ratio. This increased ratio may result from an increase in membrane surface area or a decrease in hemoglobin content. Morphologically, target cells have a central, hemoglobinized area surrounded by an area of pallor. The periphery of the cell contains a band of hemoglobin.

Figure 1. Target cells or codocytes (black arrows) appear as a target with a bullseye. Dog, blood smear, Wright stain.	Figure 2. Scanning electron micrograph of blood smear with two target cells or codocytes (white arrows). Modified from Bessis M: Blood Smears Reinterpreted, Springer-Verlag, Berlin, 1977, p. 71

In mammals, target cells may be an artifact of drying larger, discoid-shaped erythrocytes. However, the presence of excessive target cells within mammalian blood smears may indicate chronic disease including liver disease and obstructive jaundice, certain endocrinopathies, iron deficiency, post-splenectomy, thalassemia (hemoglobinopathy; not reported in domestic animals), and rare congenital deficiency of lecithin-cholesterol acyl transferase.

Liver Disease

Lecithin cholesterol acyltransferase (LCAT) activity may be decreased in obstructive liver disease. Decreased enzymatic activity increases the cholesterol to phospholipase ratio, producing an absolute increase in surface area of the red blood cell membranes. In contrast, only relative membrane excess is present in patients with iron-deficiency anemia and thalassemia because the quantity of intracellular hemoglobin is reduced.²

Research studies have shown that rats fed sunflower oil have a higher percentage of codocytes in the blood smear and these cells have a greater than normal surface area to volume ratio. The surface area to volume ratio also is elevated in iron deficiency anemia, thalassemia, and lecithin-cholesterol acyltransferase deficiency in which non-esterified cholesterols are elevated.³

Post-Splenectomy

A major function of the spleen is the clearance of opsonized, deformed, and damaged erythrocytes by splenic macrophages. If splenic macrophage function is abnormal or absent because of splenectomy, altered erythrocytes will not be removed from the circulation efficiently. Therefore, increased numbers of target cells may be observed.

Thalassemia

Thalassemia (hemoglobinopathy) is reported in human beings, but has not yet been described in domestic animals. These genetic disorders result in defects of the globin chains that are attached to the heme moiety. Thalassemia is reported mainly in descendants of the Mediterranean area, Asia, and Africa. Thalassemia is classified as an alpha or beta type. Alpha thalassemia is characterized by defects in alpha globin chains, while beta thalassemia (also known as Cooley’s anemia), is caused by defects in the beta globin chains.

Conclusion

The presence of target cells or codocytes is associated with an altered surface membrane area to volume ratio. Absolute increases in surface membrane are usually attributed to disorders of lipid metabolism (decreased lecithin cholesterol acyltransferase activity, liver disease). Decreased cytoplasmic volume is associated with decreased production of hemoglobin (iron deficiency) or manufacture of defective hemoglobin (thalassemia). Finally, the appearance of target cells may occur when splenic function is absent (post-splenectomy) or impaired.

References

1. Canfield PJ: Comparative cell morphology in the peripheral blood film from exotic and native animals. Aust Vet J 76:793-800, 1998.

2. Beutler E, Lichtman MA, Coller BS, Kipps TJ, (eds): Williams Hematology, 5^th ed. McGraw-Hill, Inc., New York, 1995, p. 10-14, 356-362.

3. Escudero A, Montilla JC, Garcia JM, Sanchez-Quevedo MC, Periago JL, Hortelano P, Suarez MD: Effect of dietary (n-9), (n-6) and (n-3) fatty acid on membrane lipid composition and morphology of rat erythrocytes. Biochimica et Biophysica Acta 1394:65-73,1998.

4. Bessis M: Blood Smears Reinterpreted (translated by George Brecher). Springer-Verlag, Berlin, 1977, pp. 68-70.

5. Lee GR, Bithell TC, Foester J, Athens JW, Lukens JN (eds): Wintrobe’s Clinical Hematology, 9^th ed. Lea & Febiger, Philadelphia, 1993, pp. 957-961.

6. Bunyaratvj A., Sahaphong S., Bhamarapravati N., Wasi P: Quantitative changes of red blood call shapes in relation to clinical features in thalassemia / HbE disease. Am J Clin Pathol 83:555-559, 1985.

7. Jain NC: Essentials of Veterinary Hematology. Lea & Febiger, Philadelphia, 1993, pp. 23-25 & 149-154.

Acknowledgement

Photograph of the Robin Hood Statue is from the Nottingham Photo Gallery of the Broxtowe College, High Road, Chilwell, Nottingham, UK website.

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