Haemoglobinopathies

Question 1

Describe the adult haemoglobin (Hb) molecule

Answer 1

It is made up of four chains, two alpha and two beta.

Question 2

What happens in thalassaemias?

Answer 2

Abnormalities occur in the production of globin chains

Question 3

What happens in sickle cell (HbS) and HbC diseases?

Answer 3

Abnormalities occur in the structure of globin chains

Question 4

Cause of alpha thalassaemia?

Answer 4

Failure of production of alpha chains after deletion of genes for the alpha globin chain, which are duplicated on each chromosome. Normally there are four copies and the deletions give rise to different clinical syndromes.

Question 5

Name different clinical syndromes of alpha thalassaemia

Answer 5

4 genes deleted: Hydrops fetalis (not compatible with life, Hb Barts)
3 genes deleted: Severe hypochromic microcytic anaemia (HbH disease)
2 genes deleted: Mild anaemia
1 gene deleted: Asymptomatic

Question 6

Cause and description of beta thalassaemia?

Answer 6

A group of genetic disorders ranging from beta thalassaemia major to beta thalassaemia minor.
Beta thalassaemia major (Mediterranean or Cooley’s anaemia) either has no beta chain or a small amount of beta chain. there are excess alpha chains which precipitate and shorten red cell lifespan.

Question 7

Clinical features of beta thalassaemia major?

Answer 7

Anaemia appearing 3 to 6 months after birth
Hepatosplenomegaly
Iron overload from multiple blood transfusions
Thalassaemic facies due to marrow cavity expansion

Question 8

Clinical features of beta thalassaemia minor?

Answer 8

Usually no symptoms and only mild anaemia

Question 9

Investigations for thalassaemia?

Answer 9

FBC (shows hypochromic microcytic anaemia)
Reticulocyte Count (increased)
Peripheral smear
Blood Film
Hb elecrophoresis (Reduced HbA)
Skull Radiography

Question 10

Treatment of thalassameia?

Answer 10

Lifelong blood transfusion to keep Hb elevated
Iron chelation therapy and folate supplementation
Splenectomy if gross splenomegaly
Allogenic bone marrow transplant - curative

Question 11

Describe sickle cell anaemia

Answer 11

In sickle cell anaemia, red blood cells have an abnormal, rigid, sickle shape. this reduces cell flexibility and leads to a tendency to block the microcirculation, causing infarcts

Question 12

Symptoms of sickle cell anaemia?

Answer 12

Many have few symptoms, whilst others have severe haemolytic anaemia, with periodic painful crises.
Precipitating factors for symptoms include infection,cold exercise, dehydration, stress, or surgical operations.

Question 13

Characterisation of crises

Answer 13

Painful infarcts of bone, spleen or other visceral organs, including lungs
Acute haemolytic crisis
Bone marrow may have “aplastic crisis”
Skin necrosis can occur - leg ulcers
Auto-infarction of spleen eventually happens

Question 14

Investigations for sickle cell anaemia?

Answer 14

FBC
Reticulocyte count
Bilirubin
Blood Film
Sickle solubility test
Hb electrophoresis

Question 15

Treatment of chronic disease (sickle cell)?

Answer 15

Folate Supplements
Prophylactic Antibiotics for Hyposplenic states
Hydroxycarbamide - If patient experiencing frequent crises or chronic pain
Bone marrow transplant is curative

Question 16

Management of sickle cell crises?

Answer 16

Prompt generous analgesia e.g IV opiates
Hydration with IV fluid
Oxygen by mask
Suspected infections treated with empiric antibiotics
Exchange transfusion if necessary to reduce proportion of HbS to <30%