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); HbSS 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: 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 vasoocclusion 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, HbSS; heterozygous condition, HbAS
• The heterozygote 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.