at times, orthochromic normoblasts (nucleated red blood cells [nRBCs]) prematurely. What is seen in the peripheral smear is increased polychromasia, red cells that are gray-blue and larger than normal. Polychro-matophilic macrocytes are actually reticulocytes; however, the reticulum can be visualized only when these cells are stained with supravital stain. The presence of polychromasia is an excellent indicator of bone marrow health. Polychromasia will be observed

• When the bone marrow is responding to anemia.

• When therapy is instituted for iron deficiency anemia or megaloblastic anemia.

• When the bone marrow is being stimulated as a result of a chronic hematological condition, such as thalassemia or sickle cell disorders.

Hypochromic red cells exhibit a larger than normal area of central pallor, greater than 3 pm, and are usually seen in conditions in which hemoglobin synthesis is impaired. Most hypochromic cells will have an MCHC of less than 32%. The development of hypochromia is usually a gradual process and can be seen on the peripheral smear as a delicately shaded area of hemoglobin within the red cell structure. Any starkly defined area of red cell pallor is usually artifactual and not true hypochromia. Not all hypochromic cells are microcytic, but all microcytic cells are hypochromic. Hypochromia of varying degrees can be seen in iron deficiency anemia, in the thalassemic conditions, and in the sideroblastic, iron-loading processes (Fig. 3.11).

Variations in Red Cell Shape

Shape variations in the red cell are always linked to a defined red cell pathophysiology. Abnormal red cell morphology presents the morphologist with visual

Figure 3.10 Polychromatophilic macrocyte.

Figure 3.11 Hypochromia.

42 Part I • Basic Hematology Principles clues as to what might be the source of the patient's hematological problems, whether they are hemolysis, anemia, or defective splenic function. Five distinct morphologies will be discussed. While these are not all inclusive, they represent the majority of abnormalities seen in a metropolitan population.


Spherocytes are compact red cells with a near normal MCV and an elevated MCHC, usually above 36%. They are easily recognized from the rest of the red cell background on the peripheral smear because they are dense, dark, and small (Fig. 3.12). Spherocytes arrive in the peripheral circulation via three distinct mechanisms. Individuals who have inherited abnormalities in spec-trin will have the condition hereditary spherocytosis (HS). Mature red cells in HS individuals arrive in the peripheral circulation with a normal appearance, but as they try to negotiate the splenic sinuses, the spleen, sensing the membrane imperfections, shears the exterior membrane, leaving a more compact structure, the spherocyte, which is osmotically fragile. The restructured red cell has a reduced life span, and the patient has a lifelong moderate anemia. As red cells age, pieces of membrane are lost in the senescent, or aging, process. Because red cells pass through the spleen hundreds of times in their 120-day life cycle, older and less perfect red cells are trapped by this organ and rendered as spherocytes, where they are eventually removed by the reticuloendothelial system. The final pathophysiology producing a spherocyte is antibody-coated red cells formed subsequent to an autoimmune or immune process. As antibody-coated cells percolate through the spleen, the antibody coating is removed and small amounts of red cell membrane are lost. The cell, the spherocyte, that is left to traverse the circulation is smaller, denser, and more fragile in its microenvironment.

Sickle Cells

Sickle cells are a highly recognizable red cell morphology, with their crescent shape and pointed projections at one of the terminal ends of the red cells (Fig. 3.13). Individuals who possess sickle cells have sickle hemoglobin as one component of their adult hemoglobin complement. Sickle hemoglobin, hemoglobin S, is an abnormal hemoglobin. Red cells containing this hemoglobin homozygously have a dramatically reduced life span owing to the fact that sickle hemoglobin is intractable and forms tactoids under conditions of hypoxic stress. When red cells containing hemoglobin S try to maneuver through the spleen and the kidney, the hemoglobin lines up in stiff bundles. This makes the red cell less elastic and unable to squeeze through the microcirculation of the spleen. The cell deforms, takes the sickle shape, and is permanently harmed. Many sickle cells may revert to normal disk shape upon oxygenation, but approximately 10% are unable to revert and these are labeled as irreversible sickle cells. Reversible sickle cells, on the other hand, appear in the peripheral smear as thicker, more rounded, half moon-shaped cells with no pointed projections. When properly oxygenated, they resume the normal disk-shaped structure of the red cells. Sickle cells may appear in combination with other hemoglobinopathies like hemoglobin SC and hemoglobin S-thalassemia.

Ovalocytes and Elliptocytes

Ovalocytes and elliptocytes are red cell morphologies that are often used interchangeably, yet these two dis-

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