Sickle Cell Anemia

Sickle cell anemia
An inherited, autosomal recessive hemoglobin (Hgb) disorder characterized by a DNA

substitution at the β-globin gene. Hgb is a quaternary structure composed of two α-globin
chains and two β-globin chains (α2β2). βS represents the inheritance of the sickle β -globin
gene. The Hgb produced from this substitution has a more negative charge than normal HbA
and in the deoxygenated state will aggregate and polymerize, forming sickled RBCs. Sickle cell
anemia is the homozygous (HbSS) state, which occurs when individuals inherit the mutant HbS
gene from both parents (α2βS2).
[sickle cell trait are heterozygous and have inherited the sickle cell gene from one parent and
the HbA gene from the other parent (α2βAβS)]
Fetal hemoglobin (HbF or α2γ2) is composed of two α chains and two γ chains; therefore, it is
not affected by point mutation on ß chains. Normally, the period from birth to approximately 3
to 6 months of age is marked by the replacement of γ-globin with ß-globin, giving rise to the
adult form of Hgb (HbA, α2β2). HbF binds oxygen more tightly than HbA, and it has a
decreased propensity to sickling. RBCs that contain HbF sickle less readily than cells without.
Sickled RBCs are more rigid and may become “lodged” (stopped) when passing through the
microvasculature, resulting in vascular occlusions. The sickled RBC surface has the ability to
initiate coagulation and adhere to inner walls of blood vessels.
Having the HbS gene protects heterozygous carriers from Plasmodium falciparum (malaria)
infection. The microorganism cannot parasitize abnormal red blood cells (RBCs) as easily as
normal RBCs. Consequently, persons with heterozygous sickle gene have a selective advantage
in tropical regions where malaria is endemic.
Pathophysiology:
Polymerization of deoxygenated HbS. HbS carries oxygen normally, and when oxygenated, the
solubility of HbS and HbA are the same. Once the oxygen is unloaded to the tissues, HbS
solubility decreases. This promotes interactions between the hemoglobin molecules and
polymerization, which leads to the distortion of the RBC into the characteristic crescent or
sickle shape.
Upon HbS reoxygenation, the polymers within the RBCs disappear, and the cells eventually
return to normal shape.
Patients carrying the sickle cell trait experience milder symptoms than those with sickle cell
anemia
1. Vasoocclussion reasons:
- Repeated assaults on RBCs from sickling and unsickling can lead to cell membrane
damage, loss of membrane flexibility.
- The life span of sickled RBCs is markedly shorter (10–20 days) than that of normal
RBCs (100–120 days)
- intracellular membrane viscosity of HbS-containing RBCs increases, blood viscosity
increases
- adherence to inner walls of blood vessels
resulting in tissue hypoxia
2. Obstruct blood flow to the spleen leading to functional asplenia, and increasing
infections.
- Kidney damage (impairs the kidney’s ability to concentrate urine)
-
Laboratory Evaluation:
WBC and platelet counts often are elevated
RBCs are high
Hgb 7.0 to 10.0 g/dL (anemia)
Presence of sickled cells on blood smear
Preventive measures for infections:

- Frequent hand-washing, avoiding sick contacts, and thoroughly cooking foods
- Antibiotic therapy should be instituted at the earliest sign of infection (penicillin to reduce
pneumonia) at least till the age of 5
- receive the pneumococcal 23-valent polysaccharide vaccine at 2 and 5 years of age with a
booster every 10 years
- Fluid status should be monitored to avoid dehydration (to decrease blood viscosity)
- Maintain oxygen saturation at 92%
- Physical exertion that leads to complications should be avoided
- Regular examinations, including ophthalmic, dental, renal, pulmonary, and cardiac
function, are required to monitor for organ damage
Treatment:
 Infection prophylaxis
- Immunization (vaccination for meningococcal disease, influenza vaccine)
- Pneumococcal vaccine
- Penicillin prophylaxis
 Induction of fetal hemoglobin
- Hydroxyurea is the primary agent
- Other agents are butyrates (arginine butyrate and sodium phenylbutyrate), decitabine,
clotrimazole, and erythropoietin
 Chronic transfusion therapy
- stroke prevention in pediatric patients
 Fever and infection
- Broad-spectrum antibiotic
- Fluids
- Acetaminophen or ibuprofen for fever
 Pain crisis
- Hydration
- Analgesics

Sickle Cell Anemia

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Sickle cell anemia

An inherited, autosomal recessive hemoglobin (Hgb) disorder characterized by a DNA

Preventive measures for infections:

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