Thalassaemia

Question 1

what is Hb composed of

Answer 1

Haemoglobin is a tetramer made of:

> 4 globin polypeptide chains (2 alpha 2 beta)
4 Haem units

Question 2

oncology of Hb

Answer 2

embryo and fetal Hb obtain O2 from mother Hb after birth beta starts to replace delta Hb

Question 3

Synthesis of an abnormal Hb structure is known as

Answer 3

Qualitative

Question 4

What is synthesis of an abnormal Hb structure is due to

Answer 4

Point mutation that changes amino acid composition of protein
* E.g. HbS, HbC, HbD, HbE

Question 5

Reduced rate of synthesis of normal α or β globin chains is known as

Answer 5

quantitative

Question 6

what causes Reduced rate of synthesis of normal α or β globin chains

Answer 6

Point mutation that changes amount of globin chain produced
α and β Thalassaemias

Question 7

what do haemoglobinopathies cause?

Answer 7

reduced 02 carrying capacity

Question 8

define homozygous

Answer 8

both genes carry mutation (e.g. SCD)

Question 9

define heterozygous

Answer 9

only one gene carries the mutation.
‘carriers’ Condition – ‘Trait’- less severe

Question 10

what does functioning Hb consist of

Answer 10

Functioning HB must contain two alpha and two non-alpha-like chains & rate of synthesis is equal

Question 11

what causes α -thalassaemia

Answer 11

> caused by α gene deletionson chromosome 16 leads to an impaired synthesis of chains which leads to an excess of unpaired chains

Question 12

true or false number of deletions determines the severity of the disease

Answer 12

true

Question 13

HB barts is due to

Answer 13

Production of excess gamma chains which form tetramers known as HB Bart

Question 14

HB A is due to

Answer 14

an excess of β chains known as HB H

Question 15

α thalassaemia is also known as

Answer 15

Autosomal recessive disorder

Question 16

what does α-thalassaemia lead to

Answer 16

This leads to defective foetal and adult HB

Question 17

deletions and clinical presentationsin alpha thala

Answer 17

Question 18

what is haemoglobin barts hydrops disease?

Answer 18

Hb Barts, is an abnormal type of hemoglobin that consists of four gamma globins. It is moderately insoluble, and therefore accumulates in the red blood cells. Hb Barts has an extremely high affinity for oxygen, so it cannot release oxygen to the tissue. Therefore, this makes it an inefficient oxygen carrier.a fetus will develop hydrops fetalis and normally die before or shortly after birth, unless intrauterine blood transfusion is performed

Question 19

what are the symptoms of HBH?

Answer 19

• swollen
• severe hypochromic anaemia
• enlarged spleen/liver
• cognitive issues
• lungs/heart not working

Question 20

HBH Blood film

Answer 20

Question 21

Methylene blue stain for HB H crystals in RBCs

Answer 21

Question 22

Management and Treatment α- Thalassaemia

Answer 22

Common Milder Form
> Occasional blood transfusion therapy

Severe Cases
> Regular transfusions
> Splenectomy
> Iron chelation

*Iron overload should be monitored by serum ferritin levels and by liver magnetic resonance imaging (MRI).

Question 23

characteristic of beta thalassaemia

Answer 23

β –thalassaemia is a group of hereditary blood disorders

1 in 4 offspring if both parents are carriers of the Thalassaemia trait.

Question 24

what causes β thalassaemia

Answer 24

majority of genetic lesions are point mutations

Question 25

what does β thalassaemia characteristics?

Answer 25

point mutations
> reduction/ absence of the synthesis of β globin genes
> So there is an increase in synthesis of γ which pairs with α so there is an increase in fetal Hb

Question 26

β thalassaemia gene deletionsand ckinicak presentations

Answer 26

Question 27

characteristics of β thalassaemia major that cause heinz bodies

Answer 27

> Two mutations so no β-globin synthesis
excess of alpha chains.
These are unstable and precipitate out into Heinz bodies in the cell=>forms rigid RBCs with shortened survival
This interferes with RBC maturation and these cells will enter circulation with inclusions inside them; removed by the spleen

Question 28

blood film of β thalassaemia major

Answer 28

Question 29

what is shown on a blood film of β thalassaemia

Answer 29

Question 30

what are the clinical features of thalassaemia?

Answer 30

• Severe anaemia becomes apparent at 3-6 months after birth.
• Enlargement of the liver and the spleen due to excessive RBC destruction (Hepatosplenomegaly)
• Erythropoiesis stimulated const; Expansion of bone due to marrow hyperplasia. (bossed skull)
• Iron overload and associated pathophysiology due to repeated blood transfusions.
• Growth retardation
• Pallor
• Jaundice
• Poor musculature
• Development of masses from extramedullary haematopoiesis
  -Leg ulcers

Question 31

what does a FBC show for thalassaemia

Answer 31

-hypochromic, microcytic cells and reticulocytes
- low MCV and MCH
- low Hb (absence of normal adult HB)
- fetal HB

Question 32

lab presentation of β thalassemia minors

Answer 32

> Hypochromic, microcytic picture
High Red Cell Count >5.5x1012/L (immature cells)
Mild anaemia HB 10-12g/Dl
A raised HB A2% these compensate lack of HB gene (>3.5) confirms the diagnosis
Mild anaemia that will not respond to iron supplements.

Question 33

why is it important to give appropriate treatment and diagnosis for thalassaemia

Answer 33

often confused with Fe deficient anaemia so given Fe supplements who don’t need it. It is important to discover so appropriate treatment can be given as well as to help the fetus when pregnant with a child with thalassaemia

Question 34

Treatment of β Thalassaemia major

Answer 34

> Regular transfusions can correct the anaemia and maintaining HB over 10g/dl suppresses erythropoiesis, and inhibits increased GI absorption of iron
Regular folic acid- is beneficial in patients with elevated reticulocyte counts, indicating increased utilization resulting from the hemolytic process and the high bone marrow turnover rate.
Iron chelation therapy- Chelators are small molecules that bind very tightly to metal ions. The iron chelator, desferrioxamine, is used to remove excess iron that accumulates with chronic blood transfusions splenectomy,
endocrine therapy growthhormonereplacementtherapyhasbeenusedinchildrenwiththalassaemiawhohaveshortstatureandgrowthhormonedeficiency.

• immunisation against hepatitis,
• Allogenic stem cell transplantation-from a matched family or unrelated donor

Question 35

Treatment of Thalassemia minor and intermedia

Answer 35

> Regular transfusions can correct the anaemia and maintaining HB over 10g/dl suppresses erythropoiesis, and inhibits increased GI absorption of iron
Regular folic acid- is beneficial in patients with elevated reticulocyte counts, indicating increased utilization resulting from the hemolytic process and the high bone marrow turnover rate. (INTERMEDIA)
Iron chelation therapy- Chelators are small molecules that bind very tightly to metal ions. The iron chelator, desferrioxamine, is used to remove excess iron that accumulates with chronic blood transfusions splenectomy,

Question 36

Where is haem made

Answer 36

Haem is made in the liver, muscle and RBCs

Question 37

Where is globin made

Answer 37

> Globin production localised to the RBC

Question 38

How many types of globin do humans synthesised

Answer 38

> Humans synthesise 6 different types of globin at different stages in life