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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. http://accesspharmacy.com/content.aspx?aid=8000420.
Accessed on June 13, 2012.
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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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- 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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- 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
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- 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.
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- SCD usually identified by routine neonatal screening programs.
- Infants with positive
screening should be tested 2 months later to confirm diagnosis.
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- SCD involves multiple organ systems. Clinical manifestations
depend on genotype (Table 1).
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