Haemoglobinopathies Flashcards
How is Fe overload treated in Beta-thalassaemia?
Iron chelation therapy
- Traditionally sub-cutaneous, pump 6 or 7 nights a week
- Now orally, once daily
What are anisocytotic RBCs?
Cells that are irregular in size
Can heterozygous carriers exhibit changes in blood parameters in beta-thalassaemia?
Yes
Are the majority of alpha-thalassaemias caused by large deletions or point mutations?
Large deletions
Why do alpha-thalassaemias present in utero where beta-thalassaemias don’t?
But beta globin chains aren’t a part of foetal Hb while alpha chains are
What are some sequelae of Fe accumulation in beta-thalassaemia?
Diabetes
Heart failure
Liver cirrhosis
Hypo/hyperthyroidism
Endocrine complications eg infertility
What is the problem with giving blood transfusion in beta-thalassaemia?
It exascerbates the Fe overload
How will someone with alpha – / alpha – present clinically?
Alpha-thalassaemia trait - mild anaemia
What triggers acute exacerbations of sickle cell anaemia?
Repeated cycles of deoxygenation
Explain the pathogenesis of sickle cell disease
Point mutation in Glu causes change to Val leading to HbS that aggregates in RBCs making them sticky and likely to cause vaso-occlusion of small vessels
What is the LCR?
A complex promoter like region on the globin genes
What is the only cure from beta-thalassaemia?
Bone marrow transplant
What type of anaemia do you get with sickle cell disease?
Severe normocytic or macrocytic haemolytic anaemia
Which globin chain is deficient in alpha-thalassaemia?
Alpha-globin chain
Where is early Hb produced?
Yolk sack
How does fetal Hb differ from adult Hb?
Two gamma chains instead of two betas
What is the globin chain configuration of adult haemoglobin (HbA)?
2 alpha globin chains
2 beta globin chains
Are the majority of beta-thalassaemias due to large deletions or point mutations?
Point mutations
Where do most of the aberrant RBCs get killed in beta-thalassaemia?
The bone marrow
Can carriers of sickle cell disease be identified with examination of normal blood parameters?
No, as they can be normal
What is the consequence of long term anaemia in beta-thalassaemia?
Erythropoiesis increases
> bone marrow expansion and loss of cortical bone = hair-on-end appearance of skull, frontal bossing, thinning of long bones
> hepatosplenomegaly due to extramedullarly erythropoiesis
What is hydrops fetalis?
Complete lack of any alpha chain genes - fatal before or around birth
What type of anaemia is seen in beta-thalassaemia?
Microcytic, hypochromic anaemia
Apart from anaemia, what is the other major consequence of beta-thalassaemia?
Accumulation of Fe
How frequently must blood transfusions be given in the treatment of beta-thalassaemia?
Every 3-4 weeks
What happens at a protein level in patients with beta-thalassaemia?
Homotetramers of alpha chains accumulate and precipitate in RBCs causing damage and RBCs are destroyed
What is chain configuration of HbA2?
2 alpha and 2 delta
What are Poikilocytotic RBCs?
Abnormally shaped RBCs
How can RNAi be used to treat thalassaemias?
Target alpha-globin mRNA in beta-thalassaemia to reduce the imbalance between the two chains
Why must splenectomies sometimes be performed in the treatment of beta-thalassaemia?
High rates of RBC killing and extramedullary erythropoiesis causes splenomegaly which can lead to rupture
