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Sickle cell anemia

Last updated: August 24, 2021

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Sickle cell syndromes are hereditary hemoglobinopathies. Homozygous sickle cell anemia (HbSS, autosomal recessive) is the most common variant of the sickle cell syndromes and occurs predominantly in individuals of African and East Mediterranean descent. Sickle cell trait occurs in heterozygous carriers (HbSA). Other rare variants of sickle cell syndrome occur in individuals with one HbS allele and one other allele (HbC or Hb-β thalassemia). A point mutation in the beta chain of hemoglobin leads to substitution of glutamic acid by valine, thus changing the structure (and properties) of hemoglobin. Abnormal hemoglobin polymerizes when deoxygenated, resulting in sickle-shaped erythrocytes, which cause vascular occlusion and ischemia. Sickle cell anemia manifests in early childhood with symptoms associated with vascular occlusion and hemolytic anemia. Infarctions in the spleen, kidneys, bone, CNS, and other organs are common and cause progressive loss of organ function and acute and chronic pain in affected parts of the body. Acute, painful vaso-occlusive crises are provoked by conditions associated with reduced oxygen tension. Neonatal screening for sickle cell anemia has been implemented across the U.S., allowing the diagnosis to be made before the first manifestation of the disease. In older children and adults, hemoglobin quantification tests are used to diagnose the condition. The cornerstones of treatment involve the management of painful vaso-occlusive crises, hemolytic anemia, and disease complications as well as prevention of infection. Allogeneic bone marrow transplantation is the only curative treatment option.

See also acute chest syndrome.

Epidemiological data refers to the US, unless otherwise specified.

Genetics

Hemoglobin composition in sickle cell disease

For details on hemoglobin and its variants, see “Hemoglobin synthesis” and “Hemoglobin variants” in the article “Erythrocyte morphology and hemoglobin.”

Hemoglobin Normal Sickle cell trait Sickle cell disease
HbA 95–98% 60% 0%
HbS 0% 40% 75–95%
HbF < 2% < 2% 5–25%

Pathomechanism

Sickle cell trait

Sickle cell disease

Diagnosis

Hemoglobin Globin chains Sickle cells Hemoglobin C
Sickle cell trait Sickle cell disease Hemoglobin SC disease (HbSC) HbC carrier HbC disease
HbA ααββ Absent Absent Absent
HbA2 ααδδ Absent Absent
HbF ααγγ Normal Normal Normal Absent
HbH ββββ Absent Absent Absent Absent Absent
Hb Bart γγγγ Absent Absent Absent Absent Absent
HbS ααββ ↑↑ Absent Absent
HbC ααββ Absent Absent ↑↑

Disease monitoring

Organ damage

Recurrent vascular occlusion and disseminated infarctions lead to progressive organ damage and loss of function. In homozygotes, this progress is associated with high morbidity and mortality. In heterozygotes, organ damage is very rare.

Organ system Complications
Spleen
Kidney
Skeletal
CNS
Male genitals
Lungs
Heart
Eye

Liver

As a result of repeated infarction of the spleen in sickle cell patients, the spleen is often atrophied rather than enlarged!

We list the most important complications. The selection is not exhaustive.

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Long term management

Prevent infections

Prevent vaso-occlusive crises and manage anemia

Management of acute sickle cell crisis

Curative therapy

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