Approach to the Child with Anemia

Although the incidence of iron deficiency in the United States has decreased significantly with improvements in infant nutrition, it remains an important cause of microcytic anemia, especially at ages 6–24 months. A trial of therapeutic iron is appropriate in such children, provided the dietary history is compatible with iron deficiency and the physical examination or CBC count does not suggest an alternative cause for the anemia. If this is not the case or if a trial of therapeutic iron fails to correct the anemia and microcytosis, further laboratory evaluation is warranted.
Another key element of Figure 27–1 is the use of both the reticulocyte count and the peripheral blood smear to determine whether a normocytic or macrocytic anemia is due to hemolysis. Typically hemolytic disease is associated with an elevated reticulocyte count, but some children with chronic hemolysis initially present during a period of virus-induced aplasia when the reticulocyte count is not elevated. Thus, review of the peripheral blood smear for evidence of hemolysis (eg, spherocytes, red cell fragmentation, sickle forms) is important in the evaluation of children with normocytic anemias and low reticulocyte counts. When hemolysis is suggested, the correct diagnosis may be suspected by specific abnormalities of red cell morphology or by clues from the history or physical examination. Autoimmune hemolysis is usually excluded by direct antiglobulin testing. Review of blood counts and the peripheral blood smears of the mother and father may suggest genetic disorders such as hereditary spherocytosis. Children with normocytic or macrocytic anemias, with relatively low reticulocyte counts and no evidence of hemolysis on the blood smear, usually have anemias caused by inadequate erythropoiesis in the bone marrow. The presence of neutropenia or thrombocytopenia in such children suggests the possibility of aplastic anemia, malignancy, or severe folate/vitamin B12 deficiency, and usually dictates examination of the bone marrow.
Pure red cell aplasia may be congenital (Diamond–Blackfan anemia), acquired and transient (transient erythroblastopenia of childhood), a manifestation of a systemic disease such as renal disease or hypothyroidism, or due to malnutrition or mild deficiencies of folate or vitamin B12.

Pure Red Cell Aplasia
Infants and children with normocytic or macrocytic anemia, a low reticulocyte count, and normal or elevated numbers of neutrophils and platelets should be suspected of having pure red cell aplasia. Examination of the peripheral blood smear in such cases is important because signs of hemolytic disease suggest chronic hemolysis complicated by an aplastic crisis due to parvovirus infection. Appreciation of this phenomenon is important because chronic hemolytic disease may not be diagnosed until the anemia is exacerbated by an episode of red cell aplasia and subsequent rapidly falling hemoglobin level. In such cases, cardiovascular compromise and congestive heart failure may develop quickly.
Congenital Hypoplastic Anemia (Diamond–Blackfan Anemia)
Essentials of Diagnosis & Typical Features

General Considerations
Diamond–Blackfan anemia is a relatively rare cause of anemia that usually presents in infancy or early childhood. Early diagnosis is important because treatment with corticosteroids results in increased erythropoiesis in about two-thirds of patients, thus avoiding the difficulties and complications of long-term chronic transfusion therapy. The cause is unclear; both autosomal dominant and autosomal recessive modes of inheritance occur.
Clinical Findings
Symptoms and Signs
Signs and symptoms are generally those of chronic anemia, such as pallor; congestive heart failure sometimes follows. Jaundice, splenomegaly, or other evidence of hemolysis is usually absent. Short stature or other congenital anomalies are present in one-third of patients. A wide variety of anomalies have been described; those affecting the head, face, and thumbs are the most common.
Laboratory Findings
Diamond–Blackfan anemia is characterized by severe macrocytic anemia and marked reticulocytopenia. The neutrophil count is usually normal or slightly decreased, and the platelet count is normal or elevated. The bone marrow usually shows a marked decrease in erythroid precursors but is otherwise normal. In older children, fetal hemoglobin levels are usually increased and there is evidence of persistent fetal erythropoiesis, such as the presence of the i antigen on erythrocytes. In addition, the level of adenosine deaminase in erythrocytes is elevated.
Differential Diagnosis
The principal differential diagnosis is transient erythroblastopenia of childhood. Children with Diamond–Blackfan anemia generally present at an earlier age, often have macrocytosis, and have evidence of fetal erythropoiesis and an elevated level of red cell adenosine deaminase. In addition, short stature and congenital anomalies, are not associated with transient erythroblastopenia. Lastly, transient erythroblastopenia of childhood usually resolves within 6–8 weeks of diagnosis, whereas Diamond–Blackfan anemia is a lifelong affliction. Other disorders associated with decreased red cell production such as renal failure, hypothyroidism, and the anemia of chronic disease need to be considered.
Treatment
Oral corticosteroids should be initiated as soon as the diagnosis of Diamond–Blackfan anemia is made. Two-thirds of patients will respond to prednisone, 2 mg/kg/d, and many of those who respond subsequently tolerate significant tapering of the dose. Patients who are unresponsive to prednisone require chronic transfusion therapy, which inevitably causes transfusion-induced hemosiderosis and the need for chelation with parenteral deferoxamine. Bone marrow transplantation is an alternative therapy that should be considered for transfusion-dependent patients who have HLA-matched siblings. Hematopoietic growth factors have been used in some cases with limited success. Unpredictable, spontaneous remissions occur in up to 20% of patients.
Prognosis
The prognosis for patients responsive to corticosteroids is generally good, particularly if remission is maintained with low doses of alternate-day prednisone. Patients dependent on transfusion are at risk for the complications of hemosiderosis, including death from congestive heart failure, cardiac arrhythmias, or hepatic failure. This remains a significant threat, particularly during adolescence, when compliance with nightly subcutaneous infusions of deferoxamine is often difficult to ensure.