Sickle Cell Disease

Key Features

Essentials of Diagnosis

• Neonatal screening test usually with hemoglobins FS, FSC, or FSA (S > A)

• Predominantly African, Mediterranean, Middle Eastern, Indian, or Caribbean ancestry

• Anemia, elevated reticulocyte count, usually jaundice

• Recurrent episodes of musculoskeletal or abdominal pain

• Often hepatomegaly and splenomegaly that resolves

• Increased risk of bacterial sepsis

General Considerations

• Sickle cell disease encompasses a family of disorders with manifestations secondary to the propensity of deoxygenated sickle hemoglobin (S) to polymerize

• Polymerization of sickle hemoglobin

  • Distorts erythrocyte morphology

  • Decreases red cell deformability

  • Causes a marked reduction in red cell life span

  • Increases blood viscosity

  • Predisposes to inflammation, coagulation activation, and episodes of vaso-occlusion

• Sickle cell anemia

  • Most severe sickling disorder

  • Caused by homozygosity for the sickle gene

  • Most common form of sickle cell disease

• Other clinically important sickling disorders are compound heterozygous conditions in which the sickle gene interacts with genes for hemoglobins C, D_Punjab, O_Arab, C_Harlem, or β-thalassemia

Demographics

• Overall, occurs in about 1 of every 400 African-American infants

• Eight percent of African Americans are heterozygous carriers of the sickle gene and thus have sickle cell trait

Clinical Findings

• Physical findings are normal at birth

• Symptoms are unusual before age 3–4 months because high levels of fetal hemoglobin inhibit sickling

• Moderately severe hemolytic anemia

  • May be present by age 1 year

  • Causes pallor, fatigue, and jaundice

  • Predisposes to the development of gallstones during childhood and adolescence

• Intense congestion of the spleen with sickled cells may cause splenomegaly in early childhood

  • Results in functional asplenia as early as age 3 months in sickle cell anemia

  • Places children at great risk for overwhelming infection with encapsulated bacteria, particularly pneumococci

• Acute splenic sequestration characterized by

  • Sudden enlargement of the spleen with pooling of red cells

  • Acute exacerbation of anemia

  • Shock and death (in severe cases)

• Dactylitis occurs in up to 50% of children with sickle cell anemia before age 3 years

• Recurrent episodes of abdominal and musculoskeletal pain may occur throughout life

• Overt strokes occur in about 11% of children with sickle cell anemia and tend to be recurrent

• Acute chest syndrome

  • Characterized by fever, pleuritic chest pain, and acute pulmonary infiltrates with hypoxemia

  • Caused by pulmonary infection, infarction, or fat embolism from ischemic bone marrow

• All tissues are susceptible to damage from vaso-occlusion, and multiple organ dysfunction is common by adulthood in those with sickle cell anemia or sickle β⁰-thalassemia

• Manifestations generally develop less frequently in those with SC and S β⁺-thalassemia

Diagnosis

• Baseline hemoglobin level of 7–10 g/dL

  • Seen in children with sickle cell anemia

  • May fall to life-threatening levels at the time of a splenic sequestration or aplastic crisis

  • Often occurs in association with parvovirus B19 infection

• Baseline reticulocyte count is elevated ...