Thalassaemia

Question 1

What are thalassaemias?

Answer 1

Thalassaemias are hereditary conditions in which there is reduced globin chain synthesis resulting in impaired haemoglobin production

Question 2

What are the 2 main types of thalassaemia?

Answer 2

• Alpha thalassaemias - Alpha chains affected
• Beta thalassaemias - Beta chains affected

Question 3

How can thalassaemia lead to anaemia?

Answer 3

Inadequate haemoglobin production leads to production of smaller red blood cells, causing a microcytic, hypochromic anaemia

Question 4

Describe the epidemiology of thalassaemia

Answer 4

These are the most common monogenic disorders and is a major cause of morbidity worldwide

This is much more commonly found in hotter climates such as southern asia and northern africa (May be protective against malaria)

Question 5

What are some possible complications of severe thalassaemia?

Answer 5

If severe, it can cause unbalanced accumulation of globin chains which are toxic to the cell, as well as ineffective erythropoiesis and haemolysis

Question 6

What is alpha thalassaemia?

Answer 6

Alpha thalassaemia is a form of thalassaemia in which alpha chain synthesis is affected

Question 7

What symbol is given to a chromosome containing 1 functional alpha gene and 1 missing alpha gene?

Answer 7

α+

Question 8

What symbol is given to a chromosome containing 2 missing alpha genes?

Answer 8

αº

Question 9

What are the 4 main classes of alpha thalassaemia?

Answer 9

• Silent α-thalassaemia
• Thalassaemia trait
• Haemoglobin H (HbH) disease
• Haemoglobin Barts Hydrops Fetalis

Question 10

What is the genetic makeup of a person with silent α-thalassaemia?

Answer 10

(α α+)

Question 11

How will silent α-thalassaemia present?

Answer 11

This will cause no symptoms, however, it makes the person a carrier, meaning they may pass it onto their offspring

Question 12

What are the possible genetic makeups of thalassaemia trait?

Answer 12

(α+ α+) or (α αº)

Question 13

How will thalassaemia trait present?

Answer 13

This is also an asymptomatic carrier state, but can cause microcytic hypochromic red cells

Ferritin will, however, be normal

Question 14

What is the genetic makeup of haemoglobin H (HbH) disease?

Answer 14

(α+ αº)

Question 15

How will haemoglobin H disease present?

Answer 15

This will cause moderate to severe anaemia due to the lack of alpha chains, so normal adult haemoglobin (HbA) cannot form

Excess ß-chains therefore form tetramers (ß4) called HbH

This can lead to jaundice, splenomegaly and may require regular transfusions

Question 16

What is the genetic makeup of haemoglobin barts hydros fetalis?

Answer 16

(αº αº)

Question 17

Describe the pathology of Hb barts hydrops fetalis?

Answer 17

This is a defect that is incompatable with life as there are no remaining alpha genes to make haemoglobin

As in HbH, disease, tetramers of Hb Barts (γ4) or HbH (ß4) produced

Question 18

What are some clinical features of haemoglobin parts hydrops fetalis?

Answer 18

• Profound anaemia
• Cardiac failure
• Growth retardation
• Severe hepatoplenomegaly
• Skeletal and cardiovascular abnormalities
• Almost all die in utero unless transfused in utero (Usually avoided)

Question 19

How is risk of Hb Barts hydrops fetalis decreased?

Answer 19

Antenatal screening is performed

Question 20

What is ß-thalassaemia?

Answer 20

Beta thalassaemia is a form of thalassaemia in which beta chain synthesis is affected

Question 21

What symbol is given to a ß gene with reduced activity?

Answer 21

ß+

Question 22

What symbol is given to a ß gene with absent activity?

Answer 22

ߺ

Question 23

What type of haemoglobin is affected in ß-thalassaemia?

Answer 23

HbA as this is the only form containing ß chains

Question 24

What are the 3 main classes of ß-thalassaemia?

Answer 24

ß-Thalassaemia trait
ß-Thalassaemia intermedia
ß-Thalassaemia major

Question 25

What genetic makeup is present in ß-thalassaemia trait?

Answer 25

(ß ß+) or (ß ßº)

Question 26

What is the clinical presentation of ß-thalassaemia trait?

Answer 26

This is an asymptomatic form of ß-thalassaemia

It can lead to mild or absent anaemia, with low MCV and raised HbA2

Question 27

What genetic makeups are present in ß-thalassaemia intermedia?

Answer 27

(ß+ ß+) or (ß+ ߺ)

Question 28

What is the clinical presentation of ß-thalassaemia intermedia?

Answer 28

This is a disease of moderate severity requiring occasional transfusion (Similar phenotype to HbH disease)

Question 29

What is the genetic makeup of ß-thalassaemia major?

Answer 29

(ߺ ߺ)

Question 30

When will ß-thalassaemias present?

Answer 30

Between 6 and 24 months as foetal haemoglobin falls

Question 31

How will ß-thalassaemia present

Answer 31

• Pallor
• Failure to thrive

Question 32

What are some symptoms of untreated, long-term ß-thalassaemia?

Answer 32

• Hepatosplenomegaly
• Skeletal changes
• Organ damage

Question 33

What causes skeletal changes in ß-thalassaemia major?

Answer 33

Increased EPO levels due to hypoxia leads to increased bone marrow activity
This causes erythroid hyperplasia and thus expansion of the medulla of bone

Question 34

What will be shown on haemoglobin analysis in ß-thalassaemia major?

Answer 34

High HbF
No HbA

Question 35

What is the management option used in ß-thalassaemia major?

Answer 35

Management of ß-thalassaemia major requires regular transfusions to maintain Hb at 95-105 to suppress ineffective erythropoiesis and inhibit over absorption of iron (Hypoxia stopped, less EPO, less erythroid hyperplasia)

Bone marrow transplant may also be used if required

Question 36

What is the highest cause of mortality in regular transfusion for ß-thalassaemia major?

Answer 36

Iron overload