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.
- 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
- 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
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
- Increases blood viscosity
- Encourages sludging in the capillaries and small vessels,
which leads to local tissue hypoxia that accentuates pathologic
- 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
- Other factors responsible for clinical manifestations of SCD
- Obstruction of blood flow to spleen, resulting in functional
- 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.
- 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 |Favorite Table|Download (.pdf)
Table 1. Clinical Features
of Sickle Cell Trait and Common Types of Sickle Cell Disease
|Sickle cell trait (SCT)||Rare painless hematuria; normal Hb level; heavy exercise under
extreme conditions can provoke gross hematuria and complications|
|Sickle cell anemia (SCA)||Pain crises, microvascular disruption of organs (spleen, liver,
bone marrow, kidney, brain, and lung), gallstones, priapism, leg
ulcers, anemia (Hb 7–10 g/dL [70–100
g/L; 4.34–6.21 mmol/L])|
|Sickle cell hemoglobin C||Painless hematuria and rare aseptic necrosis of bone; vaso-occlusive
crises less common and occur later in life; other complications
ocular disease and pregnancy-related problems; mild anemia (Hb 10–12
g/dL [100–120 g/L; 6.21–7.45
|Sickle cell β-thalassemia||Rare crises; milder severity than sickle cell disease because of
production of HbA; Hb 10–14 g/dL (100–140
g/L; 6.21–8.69 mmol/L) with microcytosis|
|Sickle cell β0-thalassemia||No HbA production; severity similar to SCA; Hb 7–10