Clinical Manifestations. Signs and symptoms of βthalassemia major result from the combination of chronic hemolytic disease, decreased or absent production of normal hemoglobin A, and ineffective erythropoiesis. The anemia is severe and leads to growth failure and high-output heart failure. Ineffective erythropoiesis causes increased expenditure of energy and expansion of the bone marrow cavities of all bones, leading to osteopenia, pathologic fractures, extramedullary erythropoiesis with resultant hepatosplenomegaly, and an increase in the rate of iron absorption.
Treatment. Treatment of β-thalassemia major is based on a hypertransfusion program that corrects the anemia and suppresses the patient’s own ineffective erythropoiesis, limiting the stimulus for increased iron absorption. This suppression permits the bones to heal, decreases metabolic expenditures, increases growth, and limits dietary iron absorption. Splenectomy may reduce the transfusion volume, but it adds to the risk of serious infection. Chelation therapy with deferoxamine or deferasirox should start when laboratory evidence of iron overload (hemochromatosis) is present and before there are clinical signs of iron overload (nonimmune diabetes mellitus, cirrhosis, heart failure, bronzing of the skin, and multiple endocrine abnormalities). Hematopoietic stem cell transplantation in childhood, before organ dysfunction induced by iron overload, has had a high success rate in β-thalassemia major and is the treatment of choice.
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Etiology and Epidemiology. The common sickle cell syndromes are hemoglobin SS disease, hemoglobin S-C disease, hemoglobin S-β thalassemia, and rare variants (Table 150-7). The specific hemoglobin phenotype must be identified because the clinical complications differ in frequency, type, and severity. As a result of a single amino acid substitution smear: hypochromic, microcytic anemia
S-HPFH Sickle-0 70–80 1–2 20–30 – Often asymptomatic; Hb F is uniformly distributed hereditary persistence of Hb F
From Andreoli T, Carpenter C, Griggs R, et al: Cecil Essentials of Medicine, ed 7, Philadelphia, 2007, Saunders.
(valine for glutamic acid at the β6 position), sickle hemoglobin crystallizes and forms a gel in the deoxygenated state. When reoxygenated, the sickle hemoglobin is normally soluble. The so-called reversible sickle cell is capable of entering the microcirculation. As the oxygen is extracted and saturation declines, sickling may occur, occluding the microvasculature. The surrounding tissue undergoes infarction, inducing pain and dysfunction. This sickling phenomenon is exacerbated by hypoxia, acidosis, fever, hypothermia, and dehydration.