Haemoglobinopathies

Expansion

“Sickle makes the wrong haemoglobin; thalassaemia makes too little of the right one.”

Sickle cell disease

• A point mutation, glutamate to valine at position 6 of the beta chain
• HbS polymerises when deoxygenated, deforming the cell
• Autosomal recessive; heterozygotes have sickle trait and are protected against falciparum malaria
• Crises: vaso-occlusive (painful), acute chest syndrome, splenic sequestration, aplastic (parvovirus B19), haemolytic
• Chronic: hyposplenism from autoinfarction, stroke, avascular necrosis, priapism, retinopathy, pulmonary hypertension, leg ulcers, gallstones
• Hydroxycarbamide raises HbF and reduces crises

Thalassaemia

• Alpha: 4 genes on chromosome 16. One or two lost is silent or trait; three lost is HbH disease; all four is Hb Barts hydrops fetalis, fatal in utero
• Beta: 2 genes on chromosome 11. Trait is mild with a raised HbA2; beta thalassaemia major presents at 6 months with severe anaemia, needing lifelong transfusion, with skull bossing and hair on end skull radiograph from marrow expansion

Iron overload from repeated transfusion is the main long term problem in thalassaemia major, requiring chelation and monitoring with ferritin and cardiac T2* MRI.