Thalassemia

Sickle Cell Anemia

A group of hemoglobin disorders resulting from the inheritance of the sickle β‐globin gene.

The sickle β‐globin abnormality is caused by substitution of valine for glutamic acid in position 6 in the β chain.
Homozygous sickle cell anaemia (Hb SS) is the most common severe syndrome while the doubly heterozygote conditions of Hb S/C and Hb S/βthal also cause sickling disease.
Hb S (Hb α2β2S ) is insoluble and forms crystals when exposed to low oxygen tension. Deoxygenated sickle hemoglobin polymerizes into long fibres, each consisting of seven intertwined double strands with cross‐linking.
The red cells sickle and may block different areas of the microcirculation or large vessels causing infarcts of various organs.
The carrier state is widespread and is found in up to 30% of West African people, maintained at this level because of the protection against malaria that is afforded by the carrier state.

The symptoms of anemia are often mild in relation to the severity of the anaemia because Hb S gives up oxygen (O2 ) to tissues relatively easily compared with Hb A.
Crises may be vaso‐occlusive (painful or visceral), aplastic or hemolytic.

Painful vaso‐occlusive crises are the most frequent.
- They may be sporadic and unpredictable or precipitated by infection, acidosis, dehydration or deoxygenation (e.g. altitude, operations, obstetric delivery, stasis of the circulation, exposure to cold, violent exercise).
- Infarcts causing severe pain occur in the bones (hips, shoulders and vertebrae are commonly affected).
- The ‘hand– foot’ syndrome (painful dactylitis caused by infarcts of the small bones) is frequently the first presentation of the disease and may lead to digits of varying lengths.
Visceral vaso‐occlusive crises are caused by sickling within organs causing infarction and pooling of blood, often with a severe exacerbation of anemia.
- The acute sickle chest syndrome is the most common cause of death both in children and adults. It presents with dyspnea, falling arterial PO2 , chest pain and pulmonary infiltrates on chest X‐ray.

These occur as a result of infection with parvovirus or from folate deficiency and are characterized by a sudden fall in hemoglobin and reticulocytes, usually requiring transfusion.

These are characterized by an increased rate of hemolysis and fall in hemoglobin but rise in reticulocytes and usually accompany a painful crisis.

The most serious is of the brain (a stroke occurs in 7% of all patients) or spinal cord. Up to a third of children have had a silent cerebral infarct by the age of 6 years.
Ulcers of the lower legs are common, as a result of vascular stasis and local ischemia.
The spleen is enlarged in infancy and early childhood but later is often reduced in size as a result of infarcts (autosplenectomy).