Thalassaemia

Question 1

Define Thalassaemia?

Answer 1

group of genetic disorders characterised by reduced globin chain synthesis

there is under or no production of one globin chain

unmatched globin chains precipitate- damaging RBC membranes causing their haemolysis whilst still in the marrow

Question 2

what is the inheritance of beta thalassaemia?

Answer 2

autosomal recessive

Question 3

outline the aetiology of thalassaemia?

Answer 3

reduced globin chain synthesis

autosomal recessive

Beta-globin gene is part of a cluster of genes on Chr11

Alpha-globin gene is part of a cluster of genes on Chr16

Result in an imbalance of globin chain production and deposition in erythroblasts and erythrocytes (membrane damage and cell destruction due to imbalance between globin chains)

This leads to:

Ineffective erythropoiesis

Haemolysis

Anaemia

Extramedullary haematopoiesis

Question 4

what are the 4 key points in the pathophysiology of thalassaemia?

Answer 4

• ineffective erythropesis
• haemolysis
• anaemia
• extramedullary haematopoeisis

Question 5

summarise the epidemiology of thalassaemia?

Answer 5

WORLDWIDE

Most common in the MEDITERRANEANand areas of the Middle-East

Question 6

what are the symptoms of beta thalassaemia major?

Answer 6

severe anaemia

Presenting at 3-6 months

• This is when the change from HbF (2alpha2gamma) to HbA (2alpha2beta) takes place
• Failure to thrive
• Prone to infection

Question 7

what is the genotype of HbF?

Answer 7

2 alpha, 2 gamma

Question 8

what is the genotype of HbA?

Answer 8

2 alpha and 2 beta

Question 9

what are the presenting symptoms of alpha thalassaemia?

Answer 9

Symp of anaemia

Hb H disease – symptoms of gallstones such as abdo pain, bloating and wind

Growth retardation with Hb H disease

Question 10

what are the symptos of alpha and beta thalassaemia trait?

Answer 10

May be ASYMPTOMATIC

Detected during routine blood tests or due to family history

Question 12

what are the signs of beta thalassaemia major on physical examination?

Answer 12

Pallor

Malaise

Dyspnoea

Mild jaundice

Extramedullary haematopoiesis occurs in response to anaemia causing frontal bossing and hepatosplenomegaly

Thalassaemia facies (facial features caused by marrow hyperplasia) - flat cranium, airspaces of sinuses and vertebral bodies)

Hepatosplenomegaly (due to erythrocyte pooling and extramedullary haematopoiesis)

Osteopenia

Patients with beta-thalassemia intermedia may also have these signs

Question 13

what are the signs of alpha thalassaemia on physical examiantion?

Answer 13

Jaundice seen with Hb H disease

Mild dysmorphic facial features (maxillary hypertrophy, frontal bossing, prominence of malar eminences)

Extramedullary haematopoesis

Question 14

what are the investigations for thalassaemia?

Answer 14

FBC

blood film

Hb Electrophoresis

Bone marrow ( beta thalassaemia )

Genetic testing ( rare) 
LFTs

Skull X-Ray and long bones X-R

Question 15

describe FBC in thalassaemia?

Answer 15

Low Hb

Low MCV (microcytic anaemia)

Low MCH

WBC count and plts somewhat elevated due to BM hyperplasia

RBC elevated with worsening genetic abnormalities

Question 16

describe the blood film in thalassaemia?

Answer 16

Hypochromic microcytic anaemia (both)

Target cells and basophilic strippling common in alpha thalassemia

Howell jolly bodies

Nucleated red cells

High reticulocyte count (both)

Question 17

Describe the Hb electrophoresis results in thalassaemia?

Answer 17

Beta-thalassemia

• Absent or reduced HbA
• High HbF and HbA2

Alpha-thalassemia

• Will not pick up trait
• Extra peak on HPLC (chromatography) due to Hb H

Question 18

describe the bone marrow in thalassaemia?

Answer 18

beta thalassemia)

• Hypercellular
• Erythroid hyperplasia

Question 19

describe LFTs in thalassaemia?

Answer 19

raised in beta-thalassemia major/intermedia (high unconjugated bilirubin, elevates LDH)

Question 20

what can be seen on skull x-ray and long bone x-ray in thalassaemia?

Answer 20

‘Hair on end’ appearance in beta thalassemia major

This is caused by expansion of marrow into the cortex

Question 21

what are the 2 main types of thalassaemia?

Answer 21

Alpha Thalassaemia- reduction in alpha globin chain synthesis.

Beta Thalassaemia

Question 22

what are the different types of alpha thalassaemia and state the presentation of each?

Answer 22

4 globin genes on the chromosome

4 gene deletion = Haemoglobin Barts Hydrops Fetalis (intrauterine death)

3 gene deletion = Haemoglobin H -> microcytic hypochromic anaemia and splenomegaly

2 gene deletion = Alpha 0 thalassemia -> microcytic hypochromic red cells, NO ANAEMIA

1 gene deletion = Alpha+ thalassemia -> microcytic hypochromic red cells, NO ANAEMIA

Question 23

what are the different types of beta thalassaemia and describe the presentation of each?

Answer 23

Beta Thalassemia Major (homozygous beta thalassemia) -> little or no beta-chain synthesis

Beta Thalassemia Intermedia - mild defect in beta-chain synthesis due to a variety of causes, e.g. co-inheritance of beta thalassemia trait with another haemoglobinopathy like HbC

Beta Thalassemia Trait (heterozygous carrier state)

Question 24

what are the features of beta thalassaemia trait

Answer 24

heterozygous carrier state

ASYMPTOMATIC

mild microcytic anaemia

increased red cell count

Question 25

what are the features of beta thalassaemia intermedia?

Answer 25

mild defect in beta-chain synthesis due to a variety of causes, e.g. co-inheritance of beta thalassemia trait with another haemoglobinopathy like HbC, leads to:

• Microcytic anaemia
• Reduced alpha-chain synthesis
• Increased gamma-chain synthesis