Thalassaemia

Question 1

Normal Hb structure

Answer 1

Haem + 2 alpha + 2 Beta

Question 2

Foetal Hb structure

Answer 2

Haem + 2 alpha + 2 gamma

Question 3

Hb delta structure

Answer 3

Haem + 2 alpha + 2 delta chains

Question 4

Percentage of normal Hb in the blood

Answer 4

97%

Question 5

Percentage of HbA2 in blood

Answer 5

2%

Question 6

Percentage of HbF in adult blood

Answer 6

1%

Question 7

What are thalassaemias

Answer 7

Genetic disease of unbalanced Hb synthesis (no production of one global chain)

Question 8

Consequence of imbalance in global chains

Answer 8

Cell damage and death of precursors in bone marrow -HAEMOLYSIS

Question 9

What is Beta and Alpha thalassaemia

Answer 9

Beta - reduced B chain synthesis

Alpha - reduced A chain synthesis

Question 10

What is the result of Beta thalassaemia having no B chains present

Answer 10

Excess alpha chains combine with delta and gamma chains

Increased HbA2 and HbF

Question 11

How is Beta thalassaemia caused

Answer 11

Point mutations - porudicing unstable B-globins that can’t be used

Question 12

What is the most common type of B-thalassaemia

Answer 12

B-thalassaemia minor - hetereozygous state

Question 13

Symptoms of BT - minor

Answer 13

Asymptomatic

Question 14

Is anaemia present in BT - nor

Answer 14

YEs but mild/almsot absent

Question 15

Appearance of RBCs

Answer 15

Hypo chromic

MICROCYTIC

Question 16

What can BT- minor be confused with

Answer 16

iron-deficiency anaemia

Question 17

How can this be distinguished from iron-deficiency anaemia

Answer 17

Serum ferritin and iron levels should be normal

Hb electrophoresis shows raised HbA2 and HbF

Question 18

What is BT- Intermedia

Answer 18

Symptomatic wit h MODERATE ANAEMIA - no transfusion required

Question 19

Clinical features of BT - Intermedia

Answer 19

Splenomegaly 
Bone deformities
Recurrent leg ulcers
Gallstones
Infections

Question 20

When does BT-major present

Answer 20

Children - homozygous

Question 21

Signs of BT-major

Answer 21

1. Recurrent bacterial infections
2. Severe anaemia from 3-6 months (when switch from gamma to beta chain usage should occur)
3. Extramedullary haemtopoiesis

Question 22

What is Extramedullary haematopoiesis

Answer 22

Ineffective RBC production outside marrow = hepatosplenomegaly and bone expansion - thalassaemic face

Question 23

Treatment of BT- major

Answer 23

Transfusion

Question 24

Result of hypertrophy of ineffective bone marrow in BT-major

Answer 24

Bone abnormalities

Question 25

What would a skull x-ray in BT-major show

Answer 25

Hair on end sign - increased marrow activity

Question 26

Blood results for BT-major

Answer 26

Microcytic

Question 27

Blood films for BT-major

Answer 27

Large + small irregular hypo chromic RBCs

Question 28

Ferritin levels in BT-major

Answer 28

Normal

Question 29

How is B-thalassaemia diagnosed

Answer 29

1. Hypochromic microcytic anaemia 2. Raised reticulocyte 3. Nucleated RBC in circulation Haemoglobin electrophoresis

Question 30

How is Beta-thalassaemia treated

Answer 30

Every2-4 weeks life-long transfusion + suppress ineffective extra medullary haematopoiesis to allow normal growth Iron-chelating agents Ascorbic acid Splenectomy Bone marrow transplant Folic acid

Question 31

What level should Hb be kept above

Answer 31

90g/L

Question 32

Name two iron-chelating agents

Answer 32

Oral DEFERIPRONE + SC DESDERRIOXAMINE

Question 33

Side-effects of iron-chelating agents

Answer 33

Pain deafness, cataracts Retinal damage

Question 34

Why are iron-chelating agents needed

Answer 34

Stop iron overload

Question 35

Why do we decrease iron loading

Answer 35

During infusions

Question 36

Why do we give ascorbic acid

Answer 36

Increase urinary excretion of iron

Question 37

When do we do a splenectomy

Answer 37

If large spleen persists with increasing transfusion

Question 38

Complications from transfusion

Answer 38

1. Progressive increase in body iron load 2. Mainly deposited in the liver + spleen reulsting in liver fibrosis + cirrhosis 3. Deposited in endocrine glands and heart = diabetes

Question 39

How are alpha-thalassaemias caused

Answer 39

Gene deletions Gene for alpha-globing chains is duplicated on chromosome 16 + one alpha chain (more common) or both alpha-chain genes can be deleted

Question 40

Clinical presentation of alpha-thalassaemia (in four gene deletion- where both genes on both chromosomes occur)

Answer 40

No alpha chain synthesis Hb BARTS present (4 gamma chains)

Question 41

What is the problem with Hb Barts

Answer 41

Can't carry O2 so incompatible with life Children are stillborn - pale, oedematous and have enormous livers + spleens)

Question 42

Consequence of 3 gene deletion in alpha-thalassaemia

Answer 42

Reduction in alpha chains = HbH increase (has four beta-chains)

Question 43

Symptoms of three gene deletion in alpha-thalaassaemia

Answer 43

MODERATE ANAEMIA SPLENOMEGALY (patient is not transfusion dependant)

Question 44

Two gene deletion alpha-thalassaemia signs

Answer 44

Microcytosis - mild anaemia

Question 45

One gene deletion alpha-thalassaemia signs

Answer 45

Normal blood