Anaemia - Alpha Thalaessemia (Microcytic)

Question 1

Definition

Answer 1

Autosomal recessive haemoglobinopathy

Question 2

Epidemiology

Answer 2

More common in:
- Sub Saharan Africa (Trans deletion)
- Mediterranean
- Middle East
- South Africa (Trans deletion)
- South East Asia (Cis deletion)

Question 3

Risk factors

Answer 3

Ethnicity from a geographic malarial area
Positive family history

Question 4

Pathophysiology

Answer 4

Less common - There are 4 genes located on chromosome 16 - 2 alpha + 2 beta

4 gene deletion = BARTS HYDROPS FETALIS
- v.high affinity for O2 so tissue don’t get O2
- oedema everywhere (esp. Liver + spleen)
- incompatible with life = stillborn

Haemoglobin H (HbH) disease = 3 gene deletion
- people with 3 gene deletions are unable to form alpha chains. The beta chains form tetramers (HbH), which damage erythrocytes causing moderate to severe disease

2 gene deletion present with
- alpha thalassemia marked anaemia
- CIS deletion = on same chromosome
- TRANS = on different
- mild symptoms, microcytosis, carrier presentation
1 gene deletion = SILENT CARRIER
- no symptoms
- can pass to children

Question 5

Symptoms

Answer 5

Fatigue
Pallor
Exertional Dyspnoea
Hepatosplenomegaly
Leg ulcers
Jaundice

Question 6

Diagnosis

Answer 6

FBC + blood film:
- Hypo-chromic RBCs
- Target cells
- Microcytic anaemia with increased reticulocytes
GOLD STANDARD = Hb electrophoresis
- bands of Hb present = HbH, HbA
Genetic testing (PCR)
- detect specific deletions
- can be done on foetal DNA by amniocentesis

Question 7

Treatment

Answer 7

FIRST LINE = blood transfusions - keep Hb high
Iron chelating agents - ORAL DEFERIPRONE