Haemolytic anaemias V: genetic defects of haemoglobin – sickle cell disease

Sickle cell disease

Sickle cell disease (homozygous sickle cell anaemia) is a chronic haemolytic anaemia caused by a point mutation in the β-globin gene resulting in substitution of valine for glutamic acid in the sixth position of the β-globin chain. This causes insolubility of Hb S in its deoxygenated state. The insoluble chains crystallize in the red cells causing sickling (Fig. 17.1) and vascular occlusion. The disease is most common in Africans (one in five West Africans are carriers – they have some protection against falciparum malaria). The mutant gene also occurs in other parts of the world where malaria is, or was, prevalent, e.g. the Middle East, Far East and the Indian subcontinent.

Clinical features

These resemble those of other chronic haemolytic anaemias, punctuated with different types of crisis.

1 Vaso-occlusive crisis is caused by increased sickling with blockage of small vessels. Common precipitants are infection, dehydration, acidosis and deoxygenation. Abdominal pain is caused by infarction affecting abdominal organs; bone pain may occur in the back, pelvis, ribs and long bones (Fig. 17.3). Infarction may affect the central nervous system – causing a stroke or fits – the lungs, spleen or kidneys. In children, the ‘hand-foot syndrome’ is caused by infarction of the metaphyses of the small bones.

2 Visceral sequestration crisis is caused by sickling with pooling of red cells in the liver, spleen or lungs. Sequestration in the lungs is partly responsible for the acute chest syndrome, though infarction and infection contribute.

3 Aplastic crisis occurs following infection by B19 parvovirus. This causes temporary arrest of erythropoiesis which in healthy individuals is of no consequence, but in patients with reduced red cell survival, such as Hb SS, can rapidly cause severe anaemia requiring blood transfusion. Folate deficiency due to increased utilization combined with poor diet may also cause anaemia.

Jun 12, 2016 | Posted by in HEMATOLOGY | Comments Off on Haemolytic anaemias V: genetic defects of haemoglobin – sickle cell disease

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