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For further information, see CMDT Part 13-13: Sickle Cell Anemia & Related Syndromes

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 resulting from vaso-occlusion by sickled RBCs occur spontaneously or 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

  • Sickle cell trait refers to patients with a heterozygous genotype (hemoglobin AS)

Demographics

  • βS gene is carried in 8% of American Blacks

  • Sickle cell anemia occurs in 1 birth in 400 in American Blacks

  • Prenatal diagnosis is available when sickle cell anemia is suspected

  • Onset during first year of life, when hemoglobin F levels fall

Clinical Findings

Symptoms and Signs

SICKLE CELL ANEMIA

  • Chronic hemolytic anemia

    • 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 (thromboembolism, acute chest syndrome, pulmonary fibrosis, radiographic interstitial abnormalities, pulmonary hypertension)

    • Liver (calcium bilirubinate gallstones, iron overload from multiple transfusions, noncirrhotic portal hypertension)

    • Bone (ischemic necrosis, staphylococcal or salmonella osteomyelitis)

    • Spleen (infarction, asplenia)

    • Kidney (infarction of renal medullary papillae, renal tubular concentrating defects, and gross hematuria, more often encountered in sickle cell trait than in sickle cell anemia)

    • Retinopathy can lead to visual impairment

  • 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 ...

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