Haem: Thalassaemia & G6PD

Question 1

What is thalassaemia?

Answer 1

Refers to a genetic defect in the protein chains that make up Hb.

Defects in the alpha globin chains –> alpha thalassaemia.

Defects in beta globin chains –> beta thalassaemia

Question 2

Inheritance of thalassaemia?

Answer 2

Autosomal recessive

Question 3

What is the overall effect of thalassaemia?

Answer 3

Varying degrees of anaemia, depending on the type and mutation.

Question 4

What causes splenomegaly in thalassaemia?

Answer 4

In patients with thalassaemia, the RBCs are more fragile and breakdown more easily.

In patients with thalassaemia, the spleen collects all the destroyed RBCs, resulting in splenomegaly (as the spleen normally acts as a sieve to filter the blood and remove older blood cells).

Question 5

How is the bone marrow affected in thalassaemia?

Answer 5

The bone marrow expands to produce extra RBCs to compensate for the chronic anaemia.

This causes a susceptibility to fractures and prominent features, such as a pronounced forehead and malar eminences (cheek bones).

Question 6

Signs & symptoms of thalassaemia?

Answer 6

• Microcytic anaemia
• Fatigue
• Pallor
• Jaundice
• Gallstones
• Splenomegaly
• Poor growth and development
• Pronounced forehead and malar eminences

Question 7

Investigations in thalassaemia?

Answer 7

1) FBC: microcytic anaemia

2) Haemoglobin electrophoresis: used to diagnose globin abnormalities

3) DNA testing: can be used to look for the genetic abnormality

Question 8

Screening for thalassaemia?

Answer 8

Pregnant woman offered screening test at booking visit.

Question 9

Management of thalassaemia?

Answer 9

Repeated transfusion

Question 10

What is a key complication of repeated transfusion in thalassaemia?

Answer 10

Iron overload –> organ failure.

Iron chelation therapy is therefore important (e.g. desferrioxamine)

Question 11

Iron overload in thalassaemia causes effects similar to haemochromatosis.

What are some symptoms?

Answer 11

• Fatigue
• Liver cirrhosis
• Infertility
• Impotence
• Heart failure
• Arthritis
• Diabetes
• Osteoporosis and joint pain

Question 12

Beta thalassaemia minor vs intermedia vs major?

Answer 12

Minor –> carriers of an abnormally functioning beta globin gene i.e. they have one abnormal and one normal gene.

Intermedia –> have two abnormal copies of the beta globin gene (can be either two defective genes or one defective gene and one deletion gene).

Major –> homozygous for the deletion genes i.e. have no functioning beta globin genes at all.

Question 13

Give 3 complications of thalassaemia major?

Answer 13

1) Severe microcytic anaemia

2) Splenomegaly

3) Bone deformities

Question 14

What can potentially be curative in thalassaemia?

Answer 14

Bone marrow transplant

Question 15

What is hereditary spherocytosis?

Answer 15

A condition where the RBCs are sphere shaped, making them fragile and easily destroyed when passing through the spleen.

Question 16

What is the most common inherited haemolytic anaemia in NORTHERN Europeans?

Answer 16

Hereditary spherocytosis

Question 17

Inheritance of hereditary spherocytosis?

Answer 17

Autosomal dominant

Question 18

Presentation of hereditary spherocytosis?

Answer 18

• Jaundice
• Anaemia
• Gallstones
• Splenomegaly

Question 19

Patients can have episodes of haemolytic crisis.

What is this?

Answer 19

These are often triggered by infections, where the haemolysis, anaemia and jaundice is more significant.

Question 20

Patients with hereditary spherocytosis can develop aplastic crisis.

What happens during aplastic crisis?

Answer 20

There is ncreased anaemia, haemolysis and jaundice, without the normal response from the bone marrow of creating new RBC.

Usually the bone marrow will respond to haemolysis by producing red blood cells faster, demonstrated by extra reticulocytes (immature red blood cells) in the blood. In aplastic crisis there is no reticulocyte response.

Question 21

What is aplastic crisis in hereditary spherocytosis typically preceeded by?

Answer 21

Infection with parvovirus

Question 22

What is seen on a blood film in hereditary spherocytosis?

Answer 22

Spherocytes

Question 23

How is the mean corpuscular haemoglobin concentration (MCHC) affected in hereditary spherocytosis?

Answer 23

Raised MCHC

Question 24

Reticulocytes in hereditary spherocytosis?

Answer 24

Raised

Question 25

Management of hereditary spherocytosis?

Answer 25

Treatment is with folate supplementation and splenectomy.

Removal of the gallbladder (cholecystectomy) may be required if gallstones are a problem.

Transfusions may be required during acute crises.

Question 26

What is G6PD deficiency?

Answer 26

There is a defect in the G6PD enzyme normally found in all cells in the body.

This causes crises that are triggered by infections, medications or fava beans (broad beans).

Question 27

Inheritance of G6PD deficiency?

Answer 27

X-linked recessive (i.e. usually affects males).

Question 28

What is the G6PD enzyme responsible for?

Answer 28

Helping protect cells from damage by reactive oxygen species (ROS).

This enzyme is particularly important in RBCs.

Question 29

What are ROS?

Answer 29

ROS are reactive molecules that contain oxygen, produced during normal cell metabolism and in higher quantities during stress on the cell.

Question 30

What is the effect of a G6PD deficiency?

Answer 30

A deficiency in G6PD makes cells more vulnerable to ROS, leading to haemolysis in red blood cells.

Periods of increased stress, with a higher production of ROS, can lead to acute haemolytic anaemia.

Question 31

How does G6PD often initially present?

Answer 31

Neonatal jaundice.

Question 32

Features of G6PD deficiency?

Answer 32

1) neonatal jaundice

2) anaemia

3) Intermittent jaundice, particularly in response to triggers

4) Gallstones

5) Splenomegaly

Question 33

What may be seen on a blood film in G6PD deficiency?

Answer 33

Heinz bodies

Question 34

What are Heinz bodies?

Answer 34

Heinz bodies are blobs of denatured haemoglobin (“inclusions”) seen within the red blood cells.

Question 35

How is a diagnosis of G6PD deficiency made?

Answer 35

G6PD enzyme assay.

Question 36

What is a key exam trigger for G6PD crisis?

Answer 36

Fava (broad) beans

Question 37

What are some medications that trigger haemolysis and should be avoided in G6PD deficiency?

Answer 37

Primaquine (an antimalarial)

Ciprofloxacin

Nitrofurantoin

Trimethoprim

Sulfonylureas (e.g gliclazide)

Sulfasalazine and other sulphonamide drugs