Sickle Cell Disease

Descriptive text is not available for this imageBASICS

DESCRIPTION

  • Sickle cell disease (SCD) is a red blood cell (RBC) disorder caused by a β-globin gene mutation. The mutation leads to a conformational change in the hemoglobin structure leading to abnormal polymerization on deoxygenation and stress.
  • Complications arise due to chronic anemia, hemolysis, and intermittent vascular occlusion causing tissue ischemia and subsequent end organ damage.

EPIDEMIOLOGY

  • SCD occurs in approximately 1 out of every 365 Black American births and approximately 1 in 16,000 Hispanic American births, with a lesser frequency in other ethnic groups.
  • The incidence of sickle cell trait (SCT) in Black Americans is 1 in 13.

RISK FACTORS

Genetics

  • SCD is autosomal recessive.
  • Hemoglobin S (sickle hemoglobin) is caused by a point mutation resulting in the substitution of valine instead of glutamic acid at position 6 on the β-globin gene on chromosome 11.
  • SCD can be caused by:
    • Homozygous inheritance of hemoglobin S (HgbSS)
    • Compound heterozygosity of hemoglobin S with another abnormal hemoglobin type (HgbSC, HgbS/β 0-thalassemia, HgbS/β +-thalassemia, HgbSD, HgbS-O Arab, etc.)

PATHOPHYSIOLOGY

  • Abnormal polymerization of the hemoglobin S molecule is the seminal event that leads to deformation of RBCs, impaired rheology, and decreased survival of RBCs.
  • Hemolysis causes release of free hemoglobin and subsequent oxidative stress resulting in vasoconstriction, inflammation, and endothelial dysfunction.
  • Increased adhesion to vascular endothelium and aggregation of RBCs with neutrophils and platelets promotes vaso-occlusion and downstream ischemia-reperfusion injury.

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