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Anemia is defined as lower than normal values of hemoglobin, or hematocrit. The lower limit of the normal range is set arbitrarily at 2 standard deviations below the mean for any given age and gender.1 The observed age and gender-related differences in the “normal” hemoglobin level during the first decade of life and after puberty (see Fig. 429-4) must be considered in making a diagnosis of anemia.2 Some laboratories use only adult normal range values and will erroneously report normal pediatric levels of hemoglobin as low. Defining anemia as a hemoglobin measurement 2 standard deviations below the mean results in 2.5% of normal children being classified as being anemic. Such individuals may track at their own low level over extended periods of time but are identified by ruling out other treatable causes. Conversely, some individuals have hemoglobin values in the lower part of the normal range that may increase after treatment with iron or after the resolution of an infectious or inflammatory process. Age-related normal means and lower limits of normal hemoglobin, hematocrit, and mean corpuscular volume (MCV) are shown in Table 429-1. Figure 429-4 depicts the pattern of normal mean hemoglobin levels from birth to adult life.

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Normal erythrocytes survive in the circulation for 100 to 120 days, therefore approximately 1% are removed from the circulation each day, and in the steady state, about 1% new erythrocytes are released into the circulation from the bone marrow each day. Anemia is the result of a congenital or acquired imbalance in erythrocyte loss relative to the marrow’s capacity for erythrocyte production. Disorders resulting in decreased erythroid production are discussed in Chapter 432, and disorders that shorten the circulating erythrocyte lifespan are discussed in Chapter 433.

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An erythrokinetic or pathophysiologic classification of anemia relies on the fact that the steady-state level of hemoglobin reflects a balance between production of red blood cells (RBCs) by the bone marrow and the rate of their peripheral destruction.1 Thus, most anemias can be classified as a disorder of marrow production or disorders of loss from the circulation (eg, hemolysis, sequestration, bleeding). The primary laboratory indicator that distinguishes these disorders is the reticulocyte count. If there is an appropriate increase in reticulocyte count from steady state in response to anemia, it suggests a disorder of loss. Conversely, if the reticulocyte count is inappropriately “normal” or low in response to anemia, it suggests and disorder of marrow production.

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A morphologic classification of anemia is based on erythrocyte size (mean corpuscular volume [MCV]) and morphology. A number of childhood anemias are associated with characteristic ERYTHROCYTE appearance, and examination of ERYTHROCYTE morphology on peripheral blood smears is an essential component of diagnosis (Fig. 430-1). A diagnostic algorithm that combines the pathophysiologic and morphologic criteria is shown in Figure 430-2.

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