RBC membrane defects

Question 1

What is G6PD deficiency?

Answer 1

An X-linked disorder that causes an inability of the RBC membrane to deal with oxidative stress, leading to haemolysis

Question 2

What is the inheritance of G6PD deficiency?

Answer 2

X-linked recessive

Question 3

What is the pathophysiology of G6PD deficiency?

Answer 3

A mutation in the G6PD enzyme makes RBCs more vulnerable to damage by reactive oxygen species. This leads to haemolysis

Question 4

What is the presentation of G6PD deficiency?

Answer 4

Anaemia
Jaundice
Gallstones
Splenomegaly
Dark urine
Fatigue and weakness

Question 5

What are common triggers for G6PD deficiency?

Answer 5

Medications
Infections
Fava beans
Chemical exposure - naphthalene and aniline dyes
Mental and physical stress

Question 6

What medications commonly trigger G6PD deficiency?

Answer 6

Antibiotics - trimethoprim, ciprofloxacin, nitrofurantoin
Aspirin
NSAIDs
Dapsone
Vitamin K analogues
Antimalarials
Sulfasalazine
Sulfonylureas

Question 7

What are the differentials of G6PD deficiency?

Answer 7

Autoimmune haemolytic anaemia
Hereditary spherocytosis
Thalassaemia

Question 8

What is seen on blood film in G6PD deficiency?

Answer 8

Heinz bodies

Question 9

What investigations are used in the diagnosis of G6PD deficiency?

Answer 9

Blood film
G6PD enzyme activity assay - definitive investigation (should be carried out 3 months after acute episode)

Question 10

What is the management of G6PD deficiency?

Answer 10

Avoiding triggers
Supportive care during acute haemolytic episode - hydration, analgesia
Blood transfusions in severe cases
Monitoring of Hb

Question 11

What are the complications of G6PD deficiency?

Answer 11

Acute haemolysis
Chronic anaemia
Susceptibility to infections

Question 12

What is hereditary spherocytosis?

Answer 12

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

Question 13

What is the presentation of hereditary spherocytosis?

Answer 13

Jaundice
Anaemia
Gallstones
Splenomegaly
Fatigue
Dizziness
Palpitations

Question 14

What is the inheritance pattern of hereditary spherocytosis?

Answer 14

Autosomal dominant

Question 15

What is the pathophysiology of hereditary spherocytosis?

Answer 15

Due to defects in the RBC membrane proteins, the RBCs appear spherical.

There is accelerated degradation of RBCs in the spleen, resulting in a normocytic anaemia.

Question 16

Why does splenomegaly occur in hereditary spherocytosis?

Answer 16

The spleen has to work harder in order to clear out the abnormal RBCs and their products

Question 17

What is the criteria for diagnosis of hereditary spherocytosis?

Answer 17

Family history of HS
and
Typical clinical features
and
Positive laboratory investigations

Question 18

What investigations are used in the diagnosis of hereditary spherocytosis?

Answer 18

FBC
Blood film - spherocytosis
LFTs - raised bilirubin
Coombs test - negative (differentiates from autoimmune haemolytic anaemia)

Question 19

What FBC results would be seen in hereditary spherocytosis?

Answer 19

Normocytic anaemia
Increased reticulocytes
Raised MCHC

Question 20

What is the management of hereditary spherocytosis?

Answer 20

Folate supplementation
Splenectomy
Transfusion may be required during acute crises

Question 21

What is hereditary elliptocytosis?

Answer 21

Similar to hereditary spherocytosis - except RBCs are ellipse shape (similar presentation and management)