Description

• Hereditary, hemoglobinopathy marked by chronic hemolytic anemia, acute episodes of painful crises, and increased susceptibility to infections
• The heterozygous condition (Hb AS), sickle cell trait, is usually asymptomatic without anemia.
• Synonym(s): sickle cell disease (SCD); Hb SS disease

Pediatric Considerations

• Sequestration crises and hand–foot syndrome are seen typically in infants/young children.
• Strokes occur mainly in childhood.
• Adolescence/young adulthood:
  • Frequency of complications and organ/tissue damage increases with age.
  • Psychological complications: body image, interrupted schooling, restriction of activities; stigma of disease; low self-esteem

Pregnancy Considerations

• Complicated, especially during 3rd trimester and delivery
  • Fetal mortality rate is 35–40%. Fetal survival is >90% if the fetus reaches the 3rd trimester.
  • High prevalence of small for gestational age (SGA) babies
  • 6 times higher maternal mortality compared to control
• Increased risk of thrombosis, preterm delivery, pain, toxemia, infection, pulmonary infarction, and phlebitis
• Partial exchange transfusion in 3rd trimester may reduce maternal morbidity and fetal mortality but is controversial.
• Chronic transfusions have been effective in diminishing pain episodes in pregnant women. However, this method should be used with caution due to risk of alloimmunization.

Epidemiology

Prevalence

• ~100,000 Americans have sickle cell anemia (SCA), and ~3 million people in the United States have sickle cell trait.
• The condition affects mainly people of African descent. Hispanic, Middle Eastern, Asian Indian, and Mediterranean ancestry may also be affected.

Etiology and Pathophysiology

• Hemoglobin S (HbS) results from the substitution of the amino acid valine for glutamic acid at the sixth position of the β-globin chain. Hydrophobic valine residues interact with other hydrophobic residues, contributing to HbS polymerization.
• HbS polymerization occurs in the RBC with increased concentrations of HbS and in deoxygenated states, resulting in RBC sickling.
• Sickle RBCs exhibit increased adhesion, are inflexible, and have decreased ability to maneuver through small vessels leading to increased blood viscosity, stasis, and vaso-occlusion of small arterioles and capillaries, resulting in ischemia.
• Chronic anemia; crises:
  • Vaso-occlusive crisis: tissue ischemia and necrosis; progressive organ failure/tissue damage from repeated episodes
  • Hand–foot syndrome: Vessel occlusion/ischemia affects small blood vessels in hands or feet.
  • Aplastic crisis: suppression of RBC production by severe infection (e.g., parvovirus and other viral infections)
  • Suppression of RBC production
  • Hyperhemolytic crisis: accelerated hemolysis with reticulocytosis; increased RBC fragility/shortened lifespan
  • Sequestration crisis: splenic sequestration of blood (only in young children as spleen is later lost to autoinfarction)
• Susceptibility to infection: impaired/absent splenic function leading to decreased ability to clear infection; defect in alternate pathway of complement activation
• Increased red cell destruction causes decreased hemoglobin levels and results in anemia and fatigue.

Genetics

• Autosomal recessive; homozygous condition, Hb SS; heterozygous condition, Hb AS
• The heterozygous condition can also be combined with other hemoglobinopathies: Sickle cell hemoglobin C (HbSC) disease and Sβ + thalassemia are clinically similar to the heterozygous condition, whereas Sβ thalassemia is clinically similar to the homozygous condition.

Risk Factors

• Vaso-occlusive crisis (“painful crisis”): hypoxia, dehydration, high altitudes, stress, fever, infection, acidosis, cold, anesthesia, strenuous physical exercise, alcohol, smoking
• Aplastic crisis (suppression of RBC production): severe infections, human parvovirus B19 infection, folic acid deficiency
• Hyperhemolytic crisis (accelerated hemolysis with reticulocytosis): acute bacterial infections, exposure to oxidant

General Prevention

• Prevention of crises
  • Avoid hypoxia, dehydration, cold, infection, fever, acidosis, and anesthesia.
  • Prompt management of fever, infections, pain
  • Avoid alcohol and smoking. Avoid high-altitude areas.
• Minimizing trauma: Aseptic technique is imperative.