Thalassemia

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.

Clinical Presentation

• 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.

Vaso‐occlusive crises

• 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.

Aplastic crises

• 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.

Hemolytic crises

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

Other organ damages

• 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).