Inherited haemolytic anaemia Flashcards
What is the usual cause for inherited haemolytic anaemia?
Dysfunction or deficiency of one of the constituents of red cell cytoskeleton
What happens if the defect is in a vertical protein?
Causes uncoupling of the lipid bilayer and reduces surface to volume ratio, causes haemolysis, a net loss of cell membrane and selective loss of portions of the lipid bilayer
What happens if the defect is in the horizontal proteins
It causes disruption of the skeletal lattice, membrane destabilisation, cell fragmentation and the formation of poikilocytes
What is the most common inherited haemolytic anaemia?
Haemoglobinopathy, which is an abnormal structure of one of the globin chains of the haemoglobin molecule
What are the two groups of haemoglobinopathies?
Thalassaemia syndrome (alpha and beta main types) and structural Hb variants. Both are caused by mutations and/or deletions in the alpha or beta globin genes. Defects in Hb synthesis cause thalassaemia, while defects in Hb structure causes qualitative defects
Where is haem made?
In the mitochondria
What chromosomes are the globin genes located on?
Alpha and zeta are located on chromosome 16, while epsilon, gamma and beta are located on chromosome 11
What will occur in the bone marrow of someone who has IHA and what will it lead to? (long answer)
The bone marrow is working hard to compensate, creating more red cell precursors, leading to an abundance of immature RBC in the blood stream (bone marrow erythroid hyperplasia). This will lead to skeletal abnormalities such as the expansion of the bone marrow, causing regular fractures due to the thinning of the calcified bone. It will also cause splenomegaly due to the spleen working hard to remove all the abnormal erythrocytes
What are the 4 types of mutations in alpha-thalassaemia?
One gene mutation - causing the output of haemoglobin to be 75% but it generally clinically silent
Alpha-thalassaemia minor - Mutation in two genes causing the alpha globulin production to fall to 50% of normal
Thalassaemia intermedia - deletion of three alpha globin genes, is the most common form
Haemoglobin Bart’s - complete loss of all four alpha genes, so the individual cannot produce any alpha globulin chains, is incompatible with life
What is HbH?
Following a mutation and lack of alpha globin chains, the excess beta globin chains precipitate and form a characteristic abnormal haemoglobin, either HbH or beta globin tetramer. HbH has a high affinity to oxygen and is unstable
What is beta thalassaemia?
A reduced or complete absence of synthesis of beta globin chains, there are more than 200 different mutations that can lead to this and can be divided into mild, silent and severe. The individual will get a constant synthesis of gamma globins leading to an increase in levels of HbF
What is the most common pathological haemoglobin varient?
HbS - structural variant of normal adult haemoglobin
What is qualitative haemoglobinopathy?
A structural change in the sequence of amino acids in the beta globin chain due to a point mutation, results from a single amino acid substitution at position 6 of the beta globin molecule to valine
What does valine do to haemoglobin molecules?
It makes them stick together, making fibres to change the whole shape of the cell
What happens to HbS under different oxygen conditions?
Under oxygenated conditions, it is fully oxygenated and soluble, but when deoxygenated it loses its solubility and polymerises into a long rigid chain that distorts the cell
