Haemoglobinopathies Flashcards
What are haemoglobinopathies?
Disorders of globin - there is no issue with haem.
What are the 3 types of haemoglobin?
HbA (2 alpha and 2 beta)
HbA2 (2 alpha and 2 delta)
HbF (2 alpha and 2 gamma)
How many alpha genes are there in each cell?
There are 4 of these per cell - 2 found on each chromosome.
Will be found on chromosome 16.
Which chromosome are the beta genes found on?
Chromosome 11
Only 2 genes are found per cell.
What pattern of inheritance is typically seen in haemoglobinopathies?
Autosomal recessive
How long does it take from birth for beta chains to begin production?
6-12 months.
Will produce Hbf before this point.
What is the problem in thalassaemias?
There is a decreased rate of globin synthesis.
What form of anaemia is caused by thalassaemia?
Microcytic hypochromic anaemia
What is alpha thalassaemia trait?
When there is 1 or 2 missing alpha genes (out of the 4 total).
Patient will be asymptomatic or only suffer from mild anaemic symptoms.
What is HbH disease?
When 3 alpha genes are missing - only one remains.
This is the most severe form of alpha thalassaemia that is compatible with life.
What is Hb Barts hydrops fetalis?
The absence of any functional alpha genes.
This is incompatible with life.
What is beta thalassaemia?
A disorder of beta chain synthesis.
This is caused by point mutations.
What type of mutation brings about alpha thalassaemia?
A deletion
What is the only form of haemoglobin affected by beta thalassaemia?
HbA
This is due to B-globins only being involved in this form of haemoglobin.
What is beta thalassaemia trait?
An asymptomatic carrier state that may only cause mild anaemia.
How is beta thalassaemia trait diagnosed?
Perform blood testing to detect raised HbA2 levels within the blood.
What is beta thalassaemia intermedia?
A moderate severity disorder that requires occasional transfusions.
What is beta thalassaemia major?
A severe condition, with patients requiring lifelong transfusions.
What should be ruled out in alpha thalassaemia trait?
Iron deficiency
Achieved by measuring ferritin levels (these are normal in alpha thalassaemia trait but low in iron-deficiency).
How are beta globins found in those with HbH disease?
Within abnormal tetramers, called HbH.
How long does it take for beta thalassaemia major to present?
6-12 months - as the body attempts to switch to HbA production.
Will cause progressive anaemia, pallor and a failure to thrive.
What is ‘frontal bossing’ characteristic of?
Extramedullary haematopoiesis
Seen as body attempts to compensate for an anaemia.
How is beta thalassaemia major treated?
Life-long transfusion.
Aim to maintain Hb between 95-105g/L.
What is a complication of regular transfusions?
Iron overload
Main cause of death in beta thalassaemia major.
How is iron overload treated?
Iron chelating agents.
These bind to iron, aiding its secretion.
Why is venesection not appropriate in beta thalassaemia major?
As these patients are already anaemic, meaning this would only make the problem at hand worse.
What are sickle cell disorders?
Disorders caused by point mutation of the beta globulin gene, resulting in production of HbS
What is the consequence of HbS?
These RBCs are stickier, meaning they can adhere to vascular endothelium more easily.
What is sickle cell trait?
The presence of an affected gene and an unaffected gene.
Essentially asymptomatic - features only present in severe hypoxia.
HbS will be seen on blood film.
What is sickle cell anaemia?
A condition caused by the inheritance of 2 abnormal genes, meaning only HbS is produced - patient has no HbA.
What is a sickle cell crisis?
Episodic tissue infarction caused by microvascular occlusion.
Patient will present with very severe pain.
What factors can precipitate a sickle cell crisis?
Hypoxia
Dehydration
Infection
Stress/Fatigue
How is sickle cell crisis treated?
Opiate analgesia (e.g. IV/SC morphine)
Hydration
Oxygen
Rest
Treat infection if present.
What is carried out if patient has severe sickle cell crisis affecting a major organ?
Red cell exchange transfusion.
Why is hydroxycarbimide given in sickle cell anaemia?
To induce HbF production.
What prophylactic steps should be taken in sickle cell anaemia?
Vaccinations
Prophylactic penicillin
Folic acid supplements
