Thalassaemia, Sickle Syndromes and Haemolytic Anaemia

Question 1

How do Thalassaemias cause a reduced Hb production?

Answer 1

by causing a reduced globin chain synthesis.

Question 2

What type of Inheritance pattern do Thalassaemias exhibit?

Answer 2

Autosomal recessive

Question 3

In which Geographical Populations are Thalassaemias more prevalent?

Answer 3

Mediterranean Europe
Central Africa
Middle East
Indian Subcontinent
South East Asia

Question 4

Having Thalassaemia trait is believed to confer some protection against which disease?

Answer 4

Falciparum Malaria

Question 5

What Arrangement of Globin chains make up Haemoglobin usually?

Answer 5

2 Alpha and 2 beta chains.

Question 6

What is the most prevalent Major form of Haemoglobin in adults?

Answer 6

HbA - 97.5%
HbA2 - 2.5%

Question 7

What Types of Chains make up the different Major Haemoglobin forms?

Answer 7

HbA - 2 alpha 2 Beta
HbA2 - 2 Alpha 2 delta
HbF - 2 Alpha 2 Gamma

Question 8

What type of Anaemia do Thalassaemia’s result in?

Answer 8

Inadequate Haemoglobin production = “Microcytic Hypochromic Anaemia”.

Question 9

How many Alpha genes would an unaffected individual have?

Answer 9

4 genes from Chromosome 16

Question 10

How many Alpha Genes would an individual with Alpha Thalassaemia trait have?

Answer 10

One or two alpha genes missing, no medical treatment needed.

• Mild hypochromic red cells with mild anaemia.
  (Important to distinguish from iron deficiency anaemia - Ferritin will be normal)

Question 11

How many Alpha genes would a patient with HbH disease have?

Answer 11

Only has one alpha gene remaining (3 defective copies).
- Moderate to severe anaemia with very low MCV and MCH.
- Excess Beta chains form tetrameres (β4) called HbH.
- Common in SE asia.

Question 12

How many Alpha genes would a patient with Hb Barts hydrops fetalis have?

Answer 12

No Functional Alpha genes.
incompatable with life.
- No Alpha chains to bind to so tetramers of Hb Barts (gamma 4) and HbH (β4) produced.

Question 13

What are some of the clinical features of Alpha Thalassaemia?

Answer 13

• Jaundice
• Facial Bone deformities
• fatigue
• Hb Barts hydrops fetalis:
  
  • Profound anaemia
  • Cardiac failure
  • Growth retardation
  • Severe hepatosplenomegaly
  • Skeletal and cardiovascular abnormalities
  • Almost all die in utero

Question 14

What would High Performance Liquid Chromatography (HPLC) or Electrophoresis show in Alpha Thalassaemia?

Answer 14

Can be normal (Because Alpha genes affect all the Heam groups), so DNA analysis is required to make the diagnosis.

Question 15

When are pregnant women offered screening for thalassaemia in the UK?

Answer 15

At booking

Question 16

What type of mutations predispose to Beta Thalassaemia?

Answer 16

Point mutations on chromosome 11.

Question 17

Which major types of Haemoglobin are affected in Beta Thalassaemias?

Answer 17

Only HbA1 (adult Haemogobin) because it is the only one in which Beta globin chains are involved.

Question 18

What does “β+” mean in terms of the number of beta genes?

Answer 18

Reduced by one.
SO β+/β would be 3 genes working and one defective/missing.

Question 19

What does “β0” mean in terms of the number of beta genes?

Answer 19

That the Gene is absent entirely. so only one copy left (on the other chromosome)
SO β0/β would only have 2 genes left.

Question 20

WHat clinical features are seen in β thalassaemia trait (β+/β or β0/β)?

Answer 20

Asymptomatic.
- Mild / No Anaemia
- Low MCV / MCH
- Raised HbA2 (DIAGNOSTIC)

Question 21

What clinical features are seen in β thalasseamia major (β0/β0)?

Answer 21

Severe symptomatic anaemia at 3-9 months of age
- Becomes evident when HbF levels fall, and HbA levels are meant to take over.

• Failure to thrive
• frontal bossing (protrusion of Frontal bone)
• Maxilliary overgrowth.
• hepatosplenomegaly due to extramedullary haematopoiesis.

Question 22

What features are seen in β thalassaemia intermedia (β+/β+ or β0/β+)?

Answer 22

Moderate severity requiring occasional transfusion.

Question 23

How is Beta Thalassaemia minor trait investigated?

Answer 23

High-performance liquid chromatography (HPLC) or electrophoresis: increased HbA2 is diagnostic!

Question 24

What are some complication of extramedullary haematopoiesis?

Answer 24

Causes cord compression.

Refers to the production of HbF by tissues such as liver, and other organs (as well as spinal cord)

Question 25

Would β-thalassaemia intermedia have an isolated microcytosis and mild anaemia? or an isolated Macrocytosis and No anaemia?

Answer 25

Mild microcytosis and Anaemia.

Question 26

which type of Thalassaemia is splenectomy indicated in?

Answer 26

HbH thalassaemia (alpha)

Question 27

In patients with more severe thalassaemias, what is the mainstay of Tx?

Answer 27

Lifelong blood transfusions to keep Hb at 95 - 105g/l.
- Suppresses ineffective erythropoiesis
- inhibits over-absorption of iron.
- Allows for normal growth and development.

Question 28

What is a complication of Thalassaemia Tx?

Answer 28

Iron overload from transfusion is the main cause of mortality.
- Half of patients with β-Thal major die before the age of 35 yrs, usually from cardiac failure secondary to iron overload.

Question 29

Target cells can be seen in which thalassaemia disease?

Answer 29

Beta Thalassaemia’s