Sickle Cell Anemia

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 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

Demographics

• Beta^S 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 skin ulcers over the lower tibia

• Anemia may be life-threatening during

  • Hemolytic or aplastic crises

  • Aplastic crises are generally associated with viral or other infection caused by

    • Immunoincompetence from hyposplenism or

    • Folic acid deficiency causing reduced erythropoiesis

• 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 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