Haemoglobinopathies

Question 1

What are haemoglobinopathies?

Answer 1

A group of inherited disorders characterised by the production of structurally abnormal haemoglobin or reduced synthesis of one or more globin chains.

Question 2

What are the two main classifications of haemoglobinopathies?

Answer 2

• Thalassaemias
• Structural haemoglobin variants

Question 3

What is the primary result of thalassaemias?

Answer 3

Imbalanced globin chain production leading to ineffective erythropoiesis and chronic haemolytic anaemia.

Question 4

What is an example of a structural haemoglobin variant?

Answer 4

Sickle cell disease.

Question 5

What type of genetic disorder is thalassaemia?

Answer 5

Autosomal recessive.

Question 6

What is the normal structure of haemoglobin?

Answer 6

Consists of 2 alpha-globin and 2 beta-globin chains.

Question 7

What happens to globin chain production in thalassaemia?

Answer 7

Globin genes are absent or mutated, leading to reduced ability to produce globin chains.

Question 8

What are the universal clinical features of thalassaemia?

Answer 8

• Microcytic anaemia (low MCV)
• Fatigue
• Pallor
• Jaundice
• Gallstones
• Splenomegaly
• Poor growth and development

Question 9

What investigations are performed for thalassaemia?

Answer 9

• FBC
• Haemoglobin electrophoresis
• DNA testing

Question 10

What causes iron overload in thalassaemia?

Answer 10

• Increased iron absorption
• Blood transfusions

Question 11

What are the types of alpha-thalassaemia?

Answer 11

• Alpha thalassaemia trait
• Haemoglobin H disease
• Alpha thalassaemia major (hydrops fetalis)

Question 12

What is a severe form of beta-thalassaemia?

Answer 12

Beta thalassaemia major, characterised by severe anaemia and failure to thrive in early childhood.

Question 13

What is sickle cell disease?

Answer 13

A group of genetic disorders (autosomal recessive) with deformed red blood cells.

Question 14

What is the most common and severe form of sickle cell disease?

Answer 14

Sickle cell anaemia.

Question 15

What triggers the polymerisation of haemoglobin S (HbS) in sickle cell disease?

Answer 15

Physiological stress such as hypoxia, dehydration, infection, cold temperature, and acidosis.

Question 16

What is a vaso-occlusive crisis in sickle cell disease?

Answer 16

A type of sickle cell crisis where sickled red blood cells obstruct capillaries, causing pain and ischaemia.

Question 17

What are the signs and symptoms of acute chest syndrome in sickle cell disease?

Answer 17

• Fever
• Cough
• Tachypnoea
• Dyspnoea
• New-onset hypoxia

Question 18

What is an aplastic crisis in sickle cell disease?

Answer 18

Temporary cessation of erythropoiesis leading to severe anaemia, usually triggered by parvovirus B19.

Question 19

What preventative measures are recommended for sickle cell disease management?

Answer 19

• Avoiding triggers like cold temperature and dehydration
• Antibiotic prophylaxis
• Vaccinations
• Folic acid supplements

Question 20

What is the purpose of hydroxycarbamide in sickle cell disease management?

Answer 20

Increases HbF production and reduces the proportion of HbS.

Question 21

What are the abnormal features associated with beta-thalassaemia major?

Answer 21

• Frontal bossing
• Enlarged maxilla
• Depressed nasal bridge
• Protruding upper teeth

Question 22

Pathophysiology of thalassaemia

Answer 22

1. reduced globin chains
2. fragile red cells break down easily (haemolytic anaemia)
3. spleen collects destroyed red cells (splenomegaly)

Question 23

What is priapism?

Relating to sickle cell disease

Answer 23

• trapping of blood in penis
• painful, persistent erection
• urological emergency, aspirate blood

Question 24

Features of hyposplenism on blood films

Answer 24

1. target cells
2. Howell-jolly bodies

Question 25

General management of sickle cell disease

Answer 25

Prevention: - avoid triggers - prophylactic penicillin V - vaccinations - folic acid supplements Medical: - blood transfusions - hydroxycarbamide - bone marrow transplant