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 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

• β^S 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 ...