Haemoglobinopathies Flashcards
What is alpha-thalassaemia?
Alpha-thalassaemia is due to a deficiency of alpha chains in haemoglobin.
How many alpha-globulin genes are located on each chromosome 16?
2 separate alpha-globulin genes are located on each chromosome 16.
What is the clinical severity of alpha-thalassaemia based on the number of affected alleles?
If 1 or 2 alpha globulin alleles are affected, the blood picture is hypochromic and microcytic, but the Hb level is typically normal. If 3 alleles are affected, it results in hypochromic microcytic anaemia with splenomegaly (Hb H disease). If all 4 alleles are affected, it leads to death in utero (hydrops fetalis, Bart’s hydrops).
What is beta-thalassaemia major?
Beta-thalassaemia major is characterized by the absence of beta globulin chains on chromosome 11.
What are the features of beta-thalassaemia major?
It presents in the first year of life with failure to thrive and hepatosplenomegaly, microcytic anaemia, raised HbA2 & HbF, and absent HbA.
What is the management for beta-thalassaemia major?
Management includes repeated transfusions, which can lead to iron overload and organ failure, making iron chelation therapy important (e.g. desferrioxamine).
What is beta-thalassaemia trait?
Beta-thalassaemia trait is an autosomal recessive condition characterized by mild hypochromic, microcytic anaemia and is usually asymptomatic.
What are the features of beta-thalassaemia trait?
It presents with mild hypochromic, microcytic anaemia, where microcytosis is disproportionately greater than the anaemia, and HbA2 is raised (> 3.5%).
What is sickle-cell anaemia?
Sickle-cell anaemia is an autosomal recessive condition resulting from the synthesis of an abnormal haemoglobin chain termed HbS.
Why is sickle-cell anaemia more common in people of African descent?
It is more common because the heterozygous condition offers some protection against malaria.
When do symptoms of sickle-cell anaemia typically develop in homozygotes?
Symptoms in homozygotes typically develop around 4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin.
What is the pathophysiology of sickle-cell anaemia?
In sickle-cell anaemia, the polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains (codon 6), decreasing the water solubility of deoxy-Hb. In the deoxygenated state, HbS molecules polymerise, causing RBCs to sickle.
At what pO2 do HbAS and HbSS patients sickle?
HbAS patients sickle at pO2 2.5 - 4 kPa, while HbSS patients sickle at pO2 5 - 6 kPa.
What happens to sickle cells in the bloodstream?
Sickle cells are fragile, haemolyse, block small blood vessels, and cause infarction.
How is sickle cell disease definitively diagnosed?
The definitive diagnosis of sickle cell disease is by haemoglobin electrophoresis.
