Sickle Cell Anemia

First Things First

  • Mutant, dysfunctional hemoglobinopathy in which valine substitutes for glutamic acid in the sixth position of the beta-globulin chain from earlier substitution of thymine for adenine in glutamic acid codon
  • This abnormal hemoglobin (Hb-S) polymerizes when O2 tensions are low and becomes insoluble.
  • In pts with full trait (Hb-SS) and subclinical traits (Hb-SC, D, SO-Arab, SA), an equilibrium exists between a physiologic dynamic fluid state and a pathologic static-gel state based on concentrations of abnormal Hb subtypes.
  • Increases in concentration of Hb-S (≥21 g/dL) cause formation of tactoid polymers, which are insoluble and hyperviscous in circulatory system.
  • This insolubility causes structural changes that distort and stiffen RBC membranes, causing them to aggregate and further amalgamate with fibrin, resulting in a gelatinous agglomeration.
  • The biological alloy also renders the RBC susceptible to adhesiveness, hemolysis, dehydration, and cellular electrolyte changes over time (influx of Na+, efflux of K+, Cl-).
  • Subclinical sickling and unsickling can also cause irreversible membrane changes that are not amenable to high O2 tensions.
  • These irreversibly deformed cells increase viscosity and change rheology; this blocks small vessels (especially capillaries and venules), leading to further crisis.
  • Immature reticulocytes from earlier hemolysis are especially vulnerable to these changes, and this can catalyze a further crisis.
  • Recurrence of any syndrome below, especially if multiple and frequent, portends a poor prognosis and shortens life span.

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Last updated: May 4, 2010