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C H A P T E R 34

APPROACH TO ANEMIA IN THE ADULT AND CHILD

Judith C. Lin

Anemia is the clinical state of low red cell mass and one of the most bloodstream and stimulates RBC production in the BM. Provided
commonly encountered laboratory findings and clinical disorders in that there are adequate nutrients, including folate, vitamin B 12 , and
hematology. Anemias encompass a broad range of clinical disorders iron, the precursors in the BM proliferate and mature and are released
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and diseases with a spectrum of subtle to severe clinical impact on into the circulation, ultimately expanding the pool of erythrocytes.
health. The approach to anemias can be direct if the cause is a The increase in oxygen delivery to the kidney then reduces the stimu-
common, singular or monogenic, easily tested and identified one; but lus for erythropoietin production.
in challenging cases, the approach may require a careful, systematic
investigation and deduction due to the diverse span of possible pathol-
ogy and pathogenesis to the red blood cell components, erythropoiesis, DEFINITION OF ANEMIA
and apoptosis. The examination of the patient’s blood cell morphology
by peripheral smear supports the analysis of anemia and is an integral Anemia is defined as a reduction in the RBC mass. Because of a
skill for anemia diagnosis. Epidemiologic studies on the global burden variety of factors, the RBC mass normally changes during the lifespan
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of anemias show that in recent decades iron deficiency accounts for of an individual and may be different in males and females. Under-
the majority of anemias, with predominance in females and the very standing the changes that occur is critical to appropriately identifying
young (under 5 years of age) having risen and the anemias of hemo- what constitutes anemia (Table 34.1). The relatively elevated level of
globinopathies, nutritional deficiency, parasitic infections, and chronic hemoglobin present at birth declines over the first 1 to 2 months of
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kidney disease significantly impacting quality of life. When analyzing life to levels that are lower than those seen in adulthood. In later
anemia in individuals the approach should be systematic and is often childhood, the hemoglobin values are similar and increase modestly
initially categorical, e.g., by relative rates of red cell production, over time. Around puberty, girls have reached adult levels of hemo-
turnover or by characteristic indices and morphologies of red blood globin, and androgenic steroids lead to a continued increase in
cells (RBCs). Additionally, the evaluation of anemia in the adult and hemoglobin in boys through about age 18 years. This approximately
child differ primarily in the changing normal ranges for red cells and 1.5 g/dL difference between males and females persists through much
hemoglobin during childhood as well as the prevalence and onset of of adult life until about age 70 years, when the hemoglobin value in
congenital hematopoietic diseases and the risks and causes of acquired men begins to decline. Over the next two decades, the hemoglobin
anemias at different ages in the adult. As population demographics value declines by about 1 g/dL in men while decreasing by only
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continuously change over time, the evaluation of anemia may also approximately 0.2 g/dL in women. Thus at age 90 years, there is
require consideration of the frequent causes of endemic origins. 2 only a modest difference between the mean hemoglobin values
The evaluation of anemia includes the initial systematic review of observed in men and women (14.1 vs. 13.8 g/dL).
laboratory data obtained from the complete blood count (CBC),
reticulocyte count, and peripheral blood smear and consideration of
the process of RBC production, erythropoiesis. MECHANISMS OF ANEMIA
Although a complete review of all of the mechanisms leading to
OVERVIEW OF ERTHROPOIESIS anemia is beyond the scope of this chapter, an appreciation of some
of the mechanisms is useful before approaching the diagnosis of
Erythropoiesis is the regulated process leading to the production of anemia in adults and children. Three broad categories of anemia are
mature RBCs or erythrocytes. Bone marrow (BM) stem cells stimu- blood loss anemia, hypoproliferative anemia, and hemolytic anemia.
lated by the hormone erythropoietin and other factors, proliferate Blood loss may occur acutely or chronically. When blood is lost
and differentiate along a pathway of recognizable erythroid precursors acutely through hemorrhage, it may take several hours before a
that ultimately leads to extrusion of the nucleus to facilitate efficient decline in hemoglobin concentration is observed because of the time
RBC rheology after the production and accumulation of a high required for restoration of the plasma volume and equilibration.
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concentration of hemoglobin and RBC enzymes (Fig. 34.1). The Several days may elapse before an appropriate reticulocytosis is noted.
early maturing RBCs lose their residual RNA under normal condi- Chronic blood loss ultimately leads to hypoproliferative anemia
tions by degradation within a day. Special staining for RNA identifies because of iron deficiency.
these cells, termed reticulocytes that are useful for both qualitative and
quantitative measure of the relative rate of peripheral blood erythro-
poiesis. Mature RBCs survive in blood circulation 100 to 120 days Hypoproliferative Anemia
before being removed from the circulation by macrophages in the
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spleen and other cells of the reticuloendothelial system. At steady When used broadly, the term hypoproliferative anemia refers to entities
state under physiologic conditions, the production and destruction that manifest as an inability to produce an adequate number of
of erythrocytes is equivalent. This process is driven in large part by erythrocytes in response to appropriate signals. Although there are
the hormone erythropoietin, which is produced in a regulated fashion many different causes, the hallmark of hypoproliferative anemia is a
by periglomerular cells in the kidney (~90%) and constitutively by low reticulocyte count (Table 34.2). The etiology underlying this class
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the liver (~10%). Because preservation of oxygen delivery to tissues of disorders may relate to the hypoproliferation of precursors within
is so important, the oxygen-sensing regulatory proteins located in the the BM, such as may be seen when there is BM replacement (myelo-
kidney respond to decreased oxygen tension from any cause such as phthisis), or to abnormal maturation of precursors in the BM, such
blood loss, high altitude, or cardiac shunts with the production of as that which occurs in megaloblastic anemia (folate deficiency,
erythropoietin (Fig. 34.2). This hormone then travels through the vitamin B 12 deficiency, myelodysplastic syndromes [MDS], and

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