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SOURCE

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Source: Chan CYJ, Frie-Jones M. Sickle cell disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=135145372. Accessed on May 17, 2017.

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DEFINITION

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  • 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).

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ETIOLOGY

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  • 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.

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PATHOPHYSIOLOGY

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  • Clinical manifestations of SCD attributable to:

    • Impaired circulation.

    • RBC destruction.

      • Typical sickle 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.

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EPIDEMIOLOGY

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  • Most common in people with African heritage.

  • About 2 million Americans have SCT with a prevalence rate of 1 in 13 African Americans and 1 in 100 Hispanics.

  • Incidence of sickle cell gene in population correlates with historical incidence of malaria.

    • SCD gene mutation offers partial protection against malaria.

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PREVENTION AND SCREENING

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  • SCD usually identified by routine neonatal screening programs.

    • Infants with positive screening should be tested before 2 months of age to confirm diagnosis.

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RISK FACTORS

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  • Inherited disorder.

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CLINICAL PRESENTATION

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

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Table Graphic Jump Location
TABLE 1.Clinical Features of Sickle Cell Trait and Common Types of Sickle Cell Disease

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