**2. Overview of anemia**

Anemia refers to a hemoglobin (Hgb) or hematocrit (Hct) level lower than adult range or the age-adjusted range for healthy children. Normal values also vary depending on the gender and race of the patient. Since the main physiological role of red blood cells (RBCs) is to deliver oxygen to tissues, anemia is a condition where the body's metabolic demands for oxygen may not be adequately achieved. The condition is usually secondary to various pathologic processes and is not considered a disease in itself.

The causes for anemia can be broadly categorized into three pathological processes: decreased or ineffective erythropoiesis, increased hemolysis, and blood loss. However, cases where anemia is multifatorial in origin can exist. Anemia can also be further classified as microcytic, normocytic or macrocytic, referring to the mean corpuscular volume (MCV) which measures RBCs size, ranging from small, normal and large, respectively. This chapter will focus on microcytic anemia in children. The cases and information given are applicable to the general practitioner, but are aimed specifically at the pediatric gastroenterologist, focusing specifically on *severe* anemias that are *severely* microcytic, because these are the cases that impact the gastroenterologist most. An effort will be made to clarify much of the commonly thought but vague and misleading information about this condition.

A Case Based Approach to Severe Microcytic Anemia in Children 249

that iron deficiency that has not progressed to anemia is also associated with poor neurocognitive function (Akman et al., 2004; Cook & Lynch 1986; Grantham-McGregor & Ani, 2001; Oski, 1983, 1985; Pollitt et al., 1986). Many possible mechanisms for the association have been suggested and investigated, but the true etiology is unknown (Beard, 2001; Erikson et al., 2001; Ortiz et al., 2004). Whether and to what extent this poor neurocognitive function can be reversed by correcting the deficiency is debated (Akman et

Many types of anemia such as hemoglobinopathies, hemolytic anemias and iron deficiency lead to increased absorption of both iron and lead from the GI tract. Coupled with the increased incidence of pica in these anemias, one effect of anemia, including that due to iron

Students are traditional taught that the differential diagnosis of microcytic anemia includes

Figure 1 shows a general schema for distinguishing these disorder based on RBC size (MCV) and hemoglobin level. The figure is not meant to show the exact values for these disorders, but to emphasize the relative values and emphasizes their overlap. After considering some of the disorders that overlap with iron deficiency, this chapter will focus on the severe anemias that are severely microcytic, i.e. those that are most likely due to iron deficiency. Note that lead poisoning is not included in the figure because as explained below it is now considered more of a consequence than a cause of iron deficiency; sideroblastic anemia is also not seen because it is not a distinct condition and thus shows considerable heterogeneity in hemoglobin and MCV. Likewise, bone marrow failure syndromes such as Diamond-Blackfan anemia, the erythropoietin deficiency of end stage renal failure, transient erythroblastopenia of childhood, and leukemia encompass a wide variety of separate disorders with different combinations of MCV and hemoglobin, but none of these are

It is important to keep in mind that the presence of one disorder does not exclude others. For example, iron deficiency may occur in patients with thalassemia, and patients may have concomitant acute and chronic bleeding. Also, the relationship is altered by therapy; hence patients who have been partially or inadequately treated may have values that do not fit the

From a practical sense, when considering the above five disorders, the severely microcytic anemias limit this differential for the most part to the top two, and further considering only those that are severely anemic to a large extent eliminates all but the first. As we shall see, a large part of microcytic anemia in children, as in adults, and certainly the severe clinically important cases, is due to iron deficiency anemia. As will be discussed, once iron deficiency

al, 2004; Lozoff et al., 1982, 1996, 2000; Oski, 1983; Walter et al., 1989)

**3. Differential diagnosis of microcytic anemia** 

five possible conditions:

microcytic.

expected relationships.

1. Iron deficiency anemia 2. Thalassemia trait 3. Lead poisoning 4. Chronic disease 5. Sideroblastic anemia

deficiency, is the increased incidence of lead poisoning and its health effects.

There have been numerous reviews on the evaluation of anemia and microcytic anemia in children (Jain & Kamat 2009, Janus & Moerschel 2010). Although these reviews attempt to be comprehensive, they tend to be overly simplistic and misleading. Specifically with regard to microcytic anemia, the impression given is that nutritional deficiency is the most frequent cause of iron deficiency and hence microcytic anemia. Although this may be true for mild anemia, it is certainly not true for severe anemia, where blood loss is far more common. While a child with a hemoglobin of 11 g/dL and mild microcytosis may have a lack of sufficient iron in his or her diet, a hemoglobin of 5 g/dL and MCV of 55 fL cannot be due to nutrition alone. Anyone at any age with such values requires investigation for a serious condition and should not be treated with iron supplementation alone. To assume that most cases of microcytosis should be treated with supplemental iron alone is to miss the opportunity and the necessity of the proper workup for significant pathology.
