Inherited haemological disorder

Question 1

Factor V Leiden deficiency : Definition

Answer 1

1. Autosomal dominant mutation
2. Most common inherited genetic thrombophilia
3. Mutation of Factor V - more resistant to inactivation by Protein C (anticoaulant protein)

Question 2

Hereditary Spherocytosis : Definition

Answer 2

1. Autosomal dominant
2. Genetic disorder characterized by an abnormality in red blood cells (erythrocytes), leading to a spherical shape
3. Increased haemolysis in the spleen

Answer 3

1. Mutation - poor structural integrity of RBC membranes
2. Membrane instability - biconcave disc shape morphs into spherical shape
3. Reduced surface area to volume ration
4. Increased fragility - unable to withstand trauma
5. Haemolysis in the Spleen

Question 4

Hereditary spherocytosis : Clinical features

Answer 4

• failure to thrive
• jaundice, gallstones
• splenomegaly
• aplastic crisis precipitated by parvovirus infection
• degree of haemolysis variable

Question 5

Hereditary spherocytosis :Management

Answer 5

• Folate therapy
• Splenectomy

Question 6

G6PD deficiency : Definition

Answer 6

1. X-linked recessive genetic disorder
2. Common in African/Mediterrarean

Question 7

G6PD deficiency : Pathophysiology

Answer 7

1. Deficiency of the G6PD enzyme - which protects RBC from oxidative damage
2. More susceptible to damage
   * When exposed to triggers
3. Increased Haemolysis

Question 8

G6PD deficiency : Triggers

Answer 8

• Infection
• anti-malarials: primaquine
• ciprofloxacin
• sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas

Question 9

G6PD deficiency : Clinical features

Answer 9

1. neonatal jaundice is often seen
2. intravascular haemolysis
3. gallstones are common
4. splenomegaly may be present

Question 10

G6PD deficiency : Diagnosis

Answer 10

1. Blood film : Heinz bodies on blood films.
   * dark granules of denatured haemoglobin enzyme secondary to oxidative stress
2. G6PD enzyme assay

Question 11

Target cells : Causes

Answer 11

They are caused either by an increase in red cell surface area or a decrease in intracellular haemoglobin.
1. Iron-deficiency anaemia
2. Hyposplenism

Question 12

Howell-Jolly bodies

Answer 12

characteristic of decreased splenic function, such as post-splenectomy.