The production of mature red blood cells (RBCs) from hematopoietic stem cells is a tightly regulated process that is dependent on growth factors, specific niches, and physiologic needs. Erythropoiesis normally proceeds at a basal rate, allowing for the replacement of senescent RBCs, which constitute 1% of red cell mass, with young reticulocytes produced within the bone marrow. However, red cell production can be enhanced by as much as 10- to 20-fold in a variety of clinical settings in which there is decreased arterial blood oxygenation and/or oxygen delivery to the tissues. In the absence of critical components required for erythropoiesis, the bone marrow is unable to produce an adequate number of red cells, ultimately leading to anemia. Anemia may be the first hematologic finding in a child with abnormal bone marrow function; it may be the sole problem (single cytopenia) or occur in conjunction with deficits in other cell lineages (pancytopenia). The cause may be a deficiency of a required nutrient (eg, iron, folic acid, vitamin B12), the inability of the marrow to use nutrients because of concomitant medical conditions (eg, inflammation, hypothyroidism), or intrinsic bone marrow failure. Bone marrow failure may be either inherited or acquired (aplastic anemia). This chapter will highlight the causes of anemia that are due to diminished RBC production.
INITIAL WORK-UP AND DIFFERENTIAL DIAGNOSIS
The critical feature that distinguishes the anemias discussed in this chapter is the presence of an inappropriately low reticulocyte count for the degree of anemia. This is consistent with nutritional deficiencies, decreased erythropoietin levels, aplastic anemia, or inherited bone marrow failure syndromes (IBMFSs). In addition, bone marrow replacement by a benign or malignant process, including those associated with ineffective erythropoiesis (eg, congenital dyserythropoietic anemias), comprise the differential diagnosis. The absolute reticulocyte count (ARC) can be calculated by multiplying the percent reticulocytes by the RBC count/L. In a patient with anemia, ARC values within the “normal range” (generally 50–100 × 109/L) indicate an inappropriate response and suggest that there is an underlying red cell production issue due to intrinsic or extrinsic factors, or a combination of the 2. The mean corpuscular volume (MCV) is another valuable red cell index that narrows the differential diagnosis of anemia due to diminished production. It is critical, however, to check age-specific normal values for MCV and to recognize that certain diseases can present with low, normal, and/or high MCVs. Finally, the red cell distribution width (RDW) assists in differentiating whether the anemia is likely due to a mixed process (wide RDW) or from a single cause (normal RDW).
MICROCYTIC ANEMIAS WITH INAPPROPRIATELY LOW RETICULOCYTE COUNTS
In pediatric patients, the most common nutritional anemia is due to iron deficiency, which is covered in depth in Chapter 427. Anemia may also develop from lead toxicity, which causes impaired synthesis of heme, hemolysis, and shortened red cell survival. Lead ...