Description

• Hereditary chronic hemoglobinopathy marked by chronic hemolytic anemia, periodic acute episodes of painful “crises,” and increased susceptibility to intercurrent infections; generally manifesting in first 6–12 months of life
• The heterozygous condition (Hb A/S), sickle cell trait, is usually asymptomatic without anemia.
• Among the compound heterozygotes, sickle-hemoglobin C disease (HbSC) and Sβ+ thalassemia are clinically similar to the heterozygous condition, whereas Sβ° thalassemia is clinically similar to the homozygous condition.
• Synonym(s): Sickle cell disease (SCD); Hb SS disease

• Sequestration crises and hand–foot syndrome seen typically in infants/young children
• Adolescence/Young adulthood:
  • Frequency of complications and organ/tissue damage increases with age (except for strokes, which occur mostly in childhood).
  • Psychological complications: Body image, interrupted schooling, restriction of activities; stigma of disease; low self-esteem

• Usually complicated and hazardous, especially 3rd trimester and delivery:
  • Fetal survival is >90% if the fetus reaches the 3rd trimester.
• Increased risk of pain, toxemia, infection, pulmonary infarction, phlebitis
• Fetal mortality 35–40%
• Partial exchange transfusion in 3rd trimester may reduce maternal morbidity and fetal mortality, but this 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

• ~90,000 Americans have SCA and 10% of African Americans carry trait. ~1/500 African Americans and 1/1,000 Hispanics have homozygous SCA. Each year in the US, about 1/400 African American infants are born with SCD.
• Lesser risk: Middle East, Mediterranean area, and populations in India may be affected.

Risk Factors

• For vaso-occlusive crisis (“painful crisis”): Pain results from tissue ischemia and necrosis: Hypoxia, dehydration, fever, infection, acidosis, cold, anesthesia, strenuous physical exercise, smoking
• For aplastic crisis (suppression of RBC production): Severe infections, human parvovirus B19 infection, folic acid deficiency
• Hyperhemolytic crisis (accelerated hemolysis with reticulocytosis) (existence is controversial): Acute bacterial infections, exposure to oxidant drugs

Genetics
Autosomal recessive. Homozygous presence of Hb S, or sickle hemoglobin (genotype SS). Heterozygous condition Hb AS. The heterozygote condition can also be combined with other hemoglobinopathies, the most common of which are HbC and β thalassemia.

General Prevention

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

Pathophysiology

• Sickle cells are abnormally shaped, fragile RBCs. Increased red cell destruction causes an inability to maintain adequate hemoglobin levels and results in anemia and fatigue.
• Sickle cells exhibit increased adhesion and decreased ability to maneuver small vessels, leading to vaso-occlusion.

Etiology

• Substitution of valine for glutamic acid in 6th amino acid of hemoglobin β-chain. Mutation → RBCs change from biconcave to sickle shape when deoxygenated due to poor solubility of mutated hemoglobin chain.
• Sickle RBCs are inflexible, causing increased blood viscosity, stasis, obstruction of small arterioles and capillaries, and ischemia. Sickle RBCs are fragile, leading to hemolysis.
• Chronic anemia; crises:
  • Vaso-occlusive crisis (“painful 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., parvoviral 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