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Sickle cell anemia (SCA) is found primarily in children of African,
Arab, or Mediterranean descent. It is caused by a single amino acid
substitution in the sixth position of the β-globulin
chain of hemoglobin A (HbA). Children homozygous for this genetic
abnormality have classic hemoglobin SS (HbSS) disease, whereas heterozygotes
for HbS with a second β-globulin chain that is
normal are considered to have sickle cell trait. Other patients
may be heterozygous for HbS coupled with a heterozygous abnormality
causing HbC or β-thalassemia. In general, patients
with HbSC and the 90% of S/β-thalassemia
patients with some normal β chains have fewer infectious
and ischemic complications than patients with HbSS.
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The abnormal chain found in patients with SCA creates a hydrophobic region
of the hemoglobin tetramer when it is deoxygenated.1 In
this state, noncovalent polymerization of the hemoglobin molecules
creates chains that distort the shape of the membrane, causing the
characteristic sickle appearance. The altered red blood cell shape
and its associated decreased deformability cause sickle cells to
impede blood flow. This is responsible for most of the clinical
manifestations of SCA. Interruption of blood flow created by the
abnormal cells leads to poor tissue perfusion, acidosis, and hypoxia,
which cause further sickling. The need to reverse these conditions
is central to the management of SCA-related complications.
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Because fetal hemoglobin (HbF) is unaffected by these genetic
mutations, symptoms of SCA don’t appear until HbF is replaced
by the abnormal HbA. HbF predominates until 4 months of age, after
which it rapidly declines, reaching baseline low levels just before
1 year of age. One of the first organs affected by the emerging
sickle cells is the spleen. Recurrent splenic infarcts lead to a
gradual decline in splenic function between 4 and 12 months of age,
resulting in susceptibility to serious infections with encapsulated
bacteria.
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In the U.S., all neonates are screened for SCA using highly sensitive
and specific tests, so the diagnosis is rarely made in the ED. The
clinical manifestations and potential complications of SCA, however,
include symptoms that overlap considerably with diseases not related
to SCA. Therefore, the diagnostic portion of this chapter is organized
in a symptom-based fashion, and the treatment portion is grouped
by disease physiology.
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Vaso-occlusive crises causing severe extremity pain are the most
common manifestation of SCA, accounting for 79% to 91% of
ED visits.2 Common triggers include stress, cold,
dehydration, altitude, hypoxia, or illness. Pain preferentially
affects the long bones and lower back. Individual patients tend
to manifest their pain crises in characteristic locations, but the
frequency of vaso-occlusive pain crisis is variable, even among
SS homozygotes. Five percent of children with SCA account for 33% of
total episodes, averaging between 3 and 10 pain crises per year.3 Children
display variable degrees of tenderness over affected sites and may
have slight temperature elevations without true fever. Because anemia
can precipitate a crisis, patients should be assessed ...