Sickle cell disease is life-threatening autosomal recessive genetic disease. The genetic mutation results in an abnormal β-globin chain of hemoglobin A, and is known as hemoglobin S. Homozygote mutations for hemoglobin S manifest sickle cell disease, a chronic disabling disease. The disease typically manifests during infancy at 4-5 months of age.

The causative mutation in sickle cell disease primarily arose on the African continent, so, globally, most patients share an African ancestry. Additionally, there is a high incidence of sickle cell disease in individuals of Caribbean descent and those from Mediterranean countries such as Turkey, Greece, and Italy.

In the United States, sickle cell disease is the most frequently detected condition in newborn-screening programs, regardless of ethnicity. Originally as a result of the transatlantic slave trade from Africa, nearly all sickle cell disease patients in the United States are Black.

Hemoglobin S has diminished solubility and forms polymers, especially when there is low oxygen tension. This gives rise to the characteristic sickle shape of the affected red blood cells. Sickled cells are more prone to hemolysis and adherence to vascular endothelium, which leads to vascular occlusion, coagulation activation, and subsequent ischemia and tissue necrosis.

Acute presentations include:

• Vaso-occlusive crises: painful episodes of microvascular occlusion that involve joints, bones, and internal organs such as the spleen, lungs (acute chest syndrome), liver, kidneys, and central nervous system.
• Hematologic crises: due to pooling of blood in the enlarged spleen.
• Infectious crises: result from functional asplenia, predisposing to infections from encapsulated organisms.

These painful crises cause significant suffering and stigmatization for sickle cell patients, who are often unjustly described as drug seekers and accused of faking their pain. This results in inadequate treatment, as well as added stress and suffering, leading many patients to avoid care altogether. Without adequate treatment, sickle cell disease can affect any organ and is associated with decreased quality of life and a shortened life span.

Acute chest syndrome is a leading cause of mortality in patients with sickle cell and is discussed separately.

See sickle cell disease for discussion of sickle cell leg ulcers and other more chronic manifestations.