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Key Features

Essentials of Diagnosis

  • 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

General Considerations

  • 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 glutamine in the sixth position on β-globin chain

  • Sickling is caused by increased red blood cell (RBC) hemoglobin S concentration, RBC dehydration, acidosis, and hypoxemia

  • Acute painful episodes occur 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-β+-thalassemia and SS α-thalassemia also have a benign clinical course

  • Patients with heterozygous genotype (hemoglobin AS) have sickle cell trait

Demographics

  • βS 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

Clinical Findings

Symptoms and Signs

  • Chronic hemolytic anemia produces

    • Jaundice

    • Pigment (calcium bilirubinate) gallstones

    • Splenomegaly (early in life)

    • Poorly healing ulcers over the lower tibia

  • Anemia may be life-threatening during

    • Hemolytic or aplastic crises

    • Infection caused by immunoincompetence from hyposplenism

  • 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

    • Include spine, long appendicular, and thoracic bones

    • Can last hours to days and produce low-grade fever

  • 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

    • Asymptomatic most often

    • Acute vaso-occlusion occurs only under extreme conditions

    • Gross hematuria or renal tubular defect causing inability to concentrate urine may occur

Differential Diagnosis

  • Other sickle cell syndromes

    • Sickle cell trait

    • Sickle thalassemia

    • Hemoglobin SC disease

  • Osteomyelitis

  • Hematuria from other cause

  • Acute rheumatic fever

Diagnosis

Laboratory Tests

  • Hematocrit usually 20–30%

  • Peripheral blood smear: irreversibly sickled cells comprise 5–50% of RBCs; reticulocytosis (10–25%); nucleated RBCs; Howell-Jolly bodies and target cells

  • White blood cell count ...

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