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Source: Chan CYJ and Moore R. Sickle Cell Disease. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th edition. Accessed on June 13, 2012.

  • Group of hereditary disorders characterized by presence of sickle cell hemoglobin (HbS) in red blood cells (RBCs).
    • Homozygous HbS (HbSS) is sickle cell anemia (SCA).
    • Heterozygous inheritance of HbS compounded with another mutation results in:
      • Sickle cell hemoglobin C (HbSC)
      • Sickle cell β-thalassemia
      • Other rare phenotypes
  • Sickle cell trait (SCT)
    • Heterozygous inheritance of 1 normal cell and 1 sickle cell hemoglobin gene (HbAS)

  • Normal Hg (hemoglobin A [HbA]) composed of 2 α chains and 2 β chains.
  • Biochemical defect in SCD involves amino acid substitution in the β-polypeptide chain
    • Leads to sickling and related sequelae.

  • Clinical manifestations of SCD attributable to:
    • Impaired circulation
    • RBC destruction
      • Typical sickled cell survives for 10–20 days.
      • Normal RBC lifespan 100–120 days
    • Stasis of blood flow
  • Above problems directly related to RBC polymerization.
    • Allows deoxygenated hemoglobin to exist as semisolid gel.
      • Protrudes into cell membrane, distorting RBCs into sickle shapes.
        • Increases blood viscosity
        • Encourages sludging in the capillaries and small vessels, which leads to local tissue hypoxia that accentuates pathologic process.
      • Repeated cycles of sickling, upon deoxygenation, and unsickling, upon oxygenation, damage RBC membrane and cause irreversible sickling.
      • Rigid, sickled RBCs easily trapped, shortening their circulatory survival and resulting in chronic hemolysis.
    • Membrane damage
      • Promotes cell recognition by macrophages.
  • Other factors responsible for clinical manifestations of SCD
    • Obstruction of blood flow to spleen, resulting in functional asplenia.
      • Increased susceptibility to infection by encapsulation organisms
    • Deficient opsonization
    • Coagulation abnormalities

  • Most common in people with African heritage.
  • Incidence of sickle cell gene in population correlates with historical incidence of malaria.
    • SCD gene mutation offers partial protection against malaria.

  • SCD usually identified by routine neonatal screening programs.
    • Infants with positive screening should be tested 2 months later to confirm diagnosis.

  • Inherited disorder

  • SCD involves multiple organ systems. Clinical manifestations depend on genotype (Table 1).

Table 1. Clinical Features of Sickle Cell Trait and Common Types of Sickle Cell Disease

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