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Essentials of Diagnosis
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Irreversibly sickled cells on peripheral blood smear
Positive family history and lifelong personal history of hemolytic anemia
Recurrent pain episodes
Hemoglobin S is the major hemoglobin seen on electrophoresis
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General Considerations
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Autosomal recessive disorder in which abnormal hemoglobin leads to chronic hemolytic anemia with numerous clinical consequences
Single DNA base change leads to amino acid substitution of valine for glutamate in the sixth position on beta-globin chain
Sickling is caused by increased red blood cell (RBC) hemoglobin S concentration, RBC dehydration, acidosis, and hypoxemia
Acute painful episodes as a result of vaso-occlusion by sickled RBCs occur spontaneously or they are provoked by infection, dehydration, or hypoxia
Sickling is retarded markedly by hemoglobin F; high hemoglobin F levels are associated with more benign course
Patients with S-beta+-thalassemia and SS alpha-thalassemia also have a benign clinical course
Patients with heterozygous genotype (hemoglobin AS) have sickle cell trait
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BetaS gene is carried in 8% of American blacks
Sickle cell anemia occurs in 1 birth in 400 in American blacks
Onset during first year of life, when hemoglobin F levels fall
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Chronic hemolytic anemia produces
Jaundice
Pigment (calcium bilirubinate) gallstones
Splenomegaly (early in life)
Poorly healing skin ulcers over the lower tibia
Anemia may be life-threatening during
Hemolytic crises result from splenic sequestration of sickled cells (primarily in childhood, before spleen has infarcted) or with coexistent disorders such as glucose-6-phosphate dehydrogenase deficiency
Aplastic crises occur when bone marrow compensation is reduced by infection or folate deficiency
Acute painful episodes
Acute vaso-occlusion may cause priapism and strokes
Repeated vaso-occlusion affects
Heart (cardiomegaly, hyperdynamic precordium, systolic murmurs)
Lungs
Liver
Bone (ischemic necrosis, staphylococcal or salmonella osteomyelitis)
Spleen (infarction, asplenia)
Kidney (infarction of renal medullary papillae, renal tubular concentrating defects, and gross hematuria)
Acute chest syndrome
Characterized by acute chest pain, hypoxemia and pulmonary infiltrates on a chest radiograph
Must be distinguished from an infectious pneumonia
Pulmonary hypertension is associated with decreased survival
Increased susceptibility to infection occurs as a result of hyposplenism and complement defects
Sickle cell trait
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Differential Diagnosis
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