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At a glance

An inherited red blood disorder characterized by chronic hemolytic anemia and intermittent vaso-occlusion resulting in tissue ischemia with acute severe pain, infections, congestive heart failure, cerebral infarction, kidney damage with bloody urine, splenomegaly, hepatomegaly and jaundice, eye damage, and bone marrow defects. The most common type is known as sickle cell anemia (SCA).

Synonym

Drepanocytosis.

Incidence

Sickle cell disease affects over 300,000 births per annum worldwide and has been declared a public health burden by the World Health Organization (WHO). It is the most common inherited blood disorder worldwide. Sickle cell disease is more prevalent across Sub-Saharan Africa. As of 2015, about 4.4 million people have sickle cell disease (SCD), while an additional 43 million have sickle cell trait. About 80% of individuals affected with SCD cases are located in the sub-Saharan Africa. The remaining cases are located in Saudi Arabia, India, and descendants from the Caribbean, Central and South America and the Mediterranean countries. The most common form of SCD found in North America is homozygous HbS disease (HbSS), an autosomal recessive disorder first described by James B. Herrick, a Chicago physician, in 1910.

Genetic inheritance

Autosomal recessive inheritance caused by a point mutation in the hemoglobin beta gene found on chromosome 11p15.4. In 1949, the genetic transmission was determined by E. A. Beet and J. V. Neel. 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.

Pathophysiology

Sickle cell hemoglobin (HbS) is characterized by the substitution of valine for glutamic acid in the sixth position of the beta 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 a upward of 70 to 90% HbS. First signs appear after 6 months of age because fetal hemoglobin (HbF) prevents the apparition of anemia in newborns and small infants. Clinical severity improves with increased levels of HbF. Two major mechanisms are recognized: (1) a hemolytic type in HbSS patients with cerebral thrombosis, glomerulopathy, retinopathy, priapism, pulmonary hypertension, early atherosclerosis and (2) a vaso-viscosity/vaso-occlusive type in patients with additional hemoglobinopathies.

  • 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. Sickle trait is usually asymptomatic, although hematuria and inability to concentrate urine may occur. The risk of sickling is very low in these patients unless there is association with other hemoglobinopathies (Hemoglobin ...

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