An inherited blood disorder characterized by episodes
of pain, chronic hemolytic anemia, and severe infections, usually beginning
in early childhood. As a result of the vasoocclusive nature of the disease,
in the worst situation, patients may present with congestive heart failure,
cerebral infarction, kidney damage with bloody urine, splenomegaly,
hepatomegaly and jaundice, eye damage, and bone marrow defects.
There are four different types: Sickle Cell Trait;
Hemoglobin SS; Hemoglobin SC Disease; Hemoglobin Sickle Beta-Thalassemia.
Sickle Cell Anemia is the most common inherited blood
disorder in the United States, affecting 1 in 375 to 500 African Americans.
Eight percent of African Americans are affected. Homozygous HbS disease
occurs in 0.2% of African Americans, while heterozygous sickle cell trait
occurs in 8%. Globally, a quarter of a million children are born every
year with the disease. At least five haplotypes of sickle cell disease are
recognized based upon their origin: Senegal, Cameron, Benin, Central African
Republic, and India. Among these, patients from the Central African Republic
have the most severe disease and those from Senegal the least severe. Other
nationalities with sickle cell include Arabs, Greeks, Italians (mostly
southern), and Latin Americans.
Autosomal recessive inheritance caused by a
point mutation in the hemoglobin beta gene (HBB) found on chromosome
HbS is characterized by the substitution of valine
for glutamic acid in the sixth position of the B chain. When deoxygenated,
the red cells change conformation, forming a sickle shape that rheologically
favors vascular stasis and subsequently ischemia. While the red cells of
patients with sickle cell trait have less than 50% HbS, the red cells of
homozygotes may have upwards of 70 to 90% HbS. Clinical severity improves
with increased levels of fetal hemoglobin (HbF). Other Sickle Cell Diseases include
Hemoglobin SC Disease, Sickle Cell Beta-Thalassemia, and Hemoglobin SD Disease. These
diseases are often, but not always, milder than Hemoglobin SS Disease.
Sickle Trait is usually asymptomatic, although hematuria and inability to
concentrate urine may occur.
Sickle Cell Trait suggests a person who carries a sickle
hemoglobin-producing gene inherited from one parent with a normal (HbA) and
an abnormal (HbS) gene leading to Hb AS on the electrophoresis. This form
does not cause HbSS Disease. Fetal diagnosis is via chorionic villus biopsy.
Electrophoresis of umbilical cord blood is also indicated to establish the diagnosis in
neonates. Peripheral smear with sickled cells, target cells, and reticulocytosis is
characteristic. Hydroxyurea, an antitumor, is effective in preventing painful crises
because it induces the formation of fetal Hb (HbF), preventing sickling.
Vasoocclusive (painful) crises (bones, abdomen,
chest) are characteristic of this disease and caused by sickling red cells leading to
ischemia. Aplastic crisis (associated with parvovirus B19 infection) can also be seen.
Sequestration crisis (usually children, though can affect adults with Hemoglobin SC
Disease and Sickle Cell Beta-Thalassemia) is another mode of clinical presentation.
Hemolytic crisis, growth retardation, bone defects/osteomyelitis (salmonella), renal
papillary necrosis, ...