Haemaglobinopathies 2 Flashcards
What causes beta thalassaemia and what type of Hb is affected ?
- Caused by point mutations in beta globin genes on chromosome 11 leading to Reduced ( β+), or absent ( β0 ) beta chain production from one beta globin gene depending on the mutation
- i.e. unlike in alpha thalssaemia where the gene is present or not (deleted) the gene can still be present but has a mutation which results in the reduced or absent production
Only beta chain synthesis is affected ==> only HbA affected (but this is the main type of Hb)
What are the 3 main types of beta thalassaemia ?
- β thalassaemia traitn (β+ /β or β0/ β)
- β thalassaemia intermedia (β+ /β+ or β0 /β+)
- β thalassaemia major (β0 /β0)
Describe the features of beta thalassaemia trait/minor ?
- It is an asymptomatic carrier state
- No/mild anaemia (>90g/L)
- Low MCV/MCH
- Raised HbA2 (>3.5%) +/- slight increase in HbF
Describe the features of β thalassaemia intermedia
- Moderate anaemia requiring occasional transfusions
- Refer to previous deck of flashcards for other features of thalassaemias in general e.g. Low MCV/MCH
- There may be splenomegaly
What are the features of β thalassaemia major including what type of Hb is mainly seen?
Presents at 6-24 months old (as HbF falls off)
Pallor, failure to thrive
Extramedullary haematopoiesis in response to anaemia causing;
- Hepatosplenomegaly - also due to haemolysis (think in the worse types of thalassaemia you get more of this and it becomes evident e.g. in this one)
- Skeletal changes - skull bossing, osteopenia, hair sign on skull X-ray
- Organ damage
Haemoglobin analysis:
- Mainly HbF
- Minimal/absent HbA
- Variable HbA2 levels
- Target cells and nucleated RBC’s may be seen
What features are shown and what condition is it associated with ?
β thalassaemia major
- Target cells
- Hair on end sign on skull X-ray
- Skull bossing
What is the main management of β thal major and what is the target Hb for it?
Regular transfusion programme to maintain Hb at 95-105g/l which
- Suppresses ineffective extramedullary erythropoiesis/haematopoeisis (as remember this will be inresponse to the anaemia so if you correct the anaemia you stop this)
- Inhibit over-absorption of iron - as chronic anaemia drives iron absorption
This allows for normal growth (remember they are very young when they present)
If someone presents early enough with B thal major and does not have any complications from it, what management may be considered with the hope of curing the patient ?
Bone marrow transplant
What is the main problem that arises with repeated transfusions in the treatment of B thal major ?
Iron overload
What are some of the other complications which can arise due to transfusions ?
- Viral infection - HIV, Hepatitis B and C
- Alloantibodies – hard to crossmatch suitable blood
- Transfusion reactions
- Risk of sepsis
How can repeated transfusions result in iron overload ?
- Because the RBC’s given by transfusion contain a lot of iron, once the lifespan of these RBC’s is complete they are broken down and the iron in the breakdown productions is then stored
- Another lot of RBC’s is transfused and so on, we dont excrete iron very quickly ==> over time results in iron overload
What are the potential consequences of iron overload and how long does this typically take to develop ?
Usuaully takes about 10yrs to develop and results in:
Endocrine dysfunction:
- Impaired growth and pubertal development
- Diabetes
- Osteoporosis
Cardiac disease:
- Cardiomyopathy
- Arrhythmias
Liver disease:
- Cirrhosis
- Hepatocellular cancer
What is given along with the treatment of B thal major to try to prevent iron overload and in general how do they work?
Iron chelators:
- 1st line = desferrioxamine
- 2nd line = Deferiprone
Chelators bind to iron, complexes formed are excreted in urine or stool
What treatment may patinets with beta thalassaemia end having and why?
Splenectomy - due to extramedullary erythropoiesis. Hypersplenism may develop, and destruction of red cells may result in profound anaemia requiring increasing transfusions. It can reverse pancytopenia and reduce the need for transfusions.
What are sickle disorders due to and what does it result in the production of?
- It is an autosomal recessive disorder causing production of abnormal beta globin chains βs
- This alters the structure of the resulting Hb→ HbS (α2βs2) (sickle cell Hb) rather than HbA produced
What happens to HbS produced in sickle disorders when it becomes deoxygenated ?
It polymerises if exposed to low oxygen levels for a prolonged period this distorts the red cell, damaging the cell membrane and results in sickle cells which are fragile and haemolyse and also block small vessels
What are the clinical features of sickle cell anaemia ?
HbS > 80%, no HbA
Anaemia
Episodes of tissue infarction due to vascular occlusion – sickle crisis - area affected depends on where the occulsions are:
- Digits (dactylitis - inflam of fingers or toes +/- pain), bone marrow, lung, spleen, CNS infarcts can lead to stroke, seizures, cognitive defects
- Pain may be extremely severe
- persistent pain in skeleton, chest, and/or abdomen
Chronic haemolysis (can cause jaundice) – shortened RBC lifespan this is usually well tolerated
- Sequestration of sickled RBCs in liver and spleen
- Hyposplenism due to repeated splenic infarcts - this can lead to increased susceptability to infection
What is the treatment of sickle cell crisis ?
- Opiate analgesia
- Hydration
- Rest
- Oxygen
- Antibiotics if evidence of infection
- Red cell exchange transfusion in severe crises eg chest crisis or neurological symptoms (pic shows this)
