haemoglobinopathies Flashcards
what is a-thalassaemia?
Alpha-thalassaemia is due to a deficiency of alpha chains in haemoglobin
where are a-chains located?
2 separate alpha-globulin genes are located on each chromosome 16
what determines the severity of a-thalassaemia?
depends on the number of alpha globulin alleles affected
describe severity of a-thalassaemia If 1 or 2 alpha globulin alleles are affected
then the blood picture would be hypochromic and microcytic, but the Hb level would be typically normal
describe severity of a-thalassaemia when 3 alpha globulin alleles are affected
hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease
describe severity of a-thalassaemia when all 4 alpha globulin alleles are affected
death in utero (hydrops fetalis, Bart’s hydrops)
what is b-thalassemia major?
absence of beta globulin chains
chromosome 11
what are features of b-thalassemia?
presents in the first year of life with failure to thrive and hepatosplenomegaly
microcytic anaemia
HbA2 & HbF raised
HbA absent
what is mx b-thalassemia?
repeated transfusion
this leads to iron overload → organ failure
iron chelation therapy is therefore important (e.g. desferrioxamine)
what is b-thalassemia trait?
The thalassaemias are a group of genetic disorders characterised by a reduced production rate of either alpha or beta chains. Beta-thalassaemia trait is an autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia. It is usually asymptomatic
what are features of b-thalassemia trait?
mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia
HbA2 raised
what is sickle cell anaemia?
Sickle-cell anaemia is an autosomal recessive condition that results for synthesis of an abnormal haemoglobin chain termed HbS. It is more common in people of African descent as the heterozygous condition offers some protection against malaria.
when do symtpoms of sickle cell develop in homozygotes?
Symptoms in homozygotes don’t tend to develop until 4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin.
what is the pathophysiology of sickle cell?
polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains (codon 6). This decreases the water solubility of deoxy-Hb
in the deoxygenated state the HbS molecules polymerise and cause RBCs to sickle
HbAS patients sickle at p02 2.5 - 4 kPa
HbSS patients at p02 5 - 6 kPa
sickle cells are fragile and haemolyse; they block small blood vessels and cause infarction
what is the inheritance of sick cell?
normal haemoglobin: HbAA
sickle cell trait: HbAS
homozygous sickle cell disease: HbSS. Some patients inherit one HbS and another abnormal haemoglobin (HbC) resulting in a milder form of sickle cell disease (HbSC)
