Figure 150-3 Genetic origins of the classic α-thalassemia syndromes due to gene deletions in the α-globin gene cluster. Hb Constant Spring (Hb CS) is an α-globin chain variant synthesized in such small amounts (1%–2% of normal) that it has the phenotypic impact of a severe non-deletion α-thalassemia allele; however, the αCS allele is always linked to a functioning α-globin gene, so it has never been associated with hydrops fetalis. (From Hoffman R, Benz EJ, Shattil SS, et al, editors: Hematology: Basic Principles and Practice, ed 5, Philadelphia, 2008, Churchill Livingstone.) ˜+-Thal trait (”Mild” trait, silent carrier) rarely causes hemolytic anemia. Detection by routine screening, removal from exposure, chelation therapy, and correction of iron deficiency are crucial to the potential development of affected children.
Etiology and Treatment. Anemia is a common component of chronic inflammatory disease. Hepcidin, a protein made in the liver, plays a key role in iron homeostasis. Inflammation causes an increase in the production of hepcidin, interrupting the process of iron release by macrophages and the absorption
Normal ˜-Thalassemia with Hb constant spring of iron from the intestines leading to anemia. The anemia of inflammation may be normocytic or, less often, microcytic. This may pose a clinical challenge, when children with inflammatory disorders associated with blood loss (inflammatory bowel disease) exhibit a microcytic anemia. In these circumstances, only a bone marrow aspiration with staining of the sample for iron can differentiate the two entities clearly (see Table 150-4). Low ferritin levels indicate concurrent iron deficiency. A trial of iron therapy is not indicated without a specific diagnosis in children who appear to be systemically ill.
Bone marrow infiltration by malignant cells commonly leads to a normochromic, normocytic anemia. The mechanism
Table 150-6 Differentiation of Red Blood Cell Aplasias and Aplastic Anemias DISORDER AGE AT ONSET CHARACTERISTICS TREATMENT CONGENITAL Diamond-Blackfan syndrome (congenital Newborn–1 mo; 90% of patients are <1 yr Pure red blood cell aplasia, autosomal recessive trait, elevated fetal hemoglobin, fetal i antigen Prednisone, transfusion, hematopoietic stem cell hypoplastic anemia) of age present, macrocytic, short stature, webbed neck, transplant cleft lip, triphalangeal thumb; late-onset leukemia, mutation analysis
Parvovirus Any age Any chronic hemolytic anemia, typically sickle cell; Transfusion new-onset reticulocytopenia
Epstein-Barr virus (EBV) Any age; usually <5 yr X-linked immunodeficiency syndrome, Transfusion, bone marrow of age pancytopenia transplantation
CMV, Cytomegalovirus; CSF, cerebrospinal fluid; HHV-6, human herpesvirus 6; IVIG, intravenous immune globulin; MCV, mean corpuscular volume; VP-16, etoposide.
by which neoplastic cells interfere with RBC and other marrow cell synthesis is multifactorial. The reticulocyte count is often low. Immature myeloid elements may be released into the peripheral blood because of the presence of the offending tumor cells. An examination of the peripheral blood may reveal lymphoblasts; when solid tumors metastasize to the marrow, these cells are seldom seen in the peripheral blood. Teardrop cells may be seen in the peripheral blood. A bone marrow examination is frequently necessary in the face of normochromic, normocytic anemia.