Lecture 4: Sickle Cell Disease (SCD) & Thalassaemia

Question 1

What are the two major types of haemoglobinopathies?

Answer 1

Qualitative (abnormal Hb structure, e.g., HbS in SCD).

Quantitative (reduced globin synthesis, e.g., α/β-thalassaemia).

Question 2

Which globin chains are affected in α- vs. β-thalassaemia?

Answer 2

α-thalassaemia: Impaired α-chain synthesis (chromosome 16).

β-thalassaemia: Impaired β-chain synthesis (chromosome 11).

Question 3

What causes Hb Bart’s hydrops fetalis?

Answer 3

Deletion of all 4 α-globin genes → excess γ-chains forming Hb Bart’s (fatal in utero).

Question 4

Lab findings in HbH disease (3 α-gene deletions)?

Answer 4

Microcytosis, HbH inclusions (methylene blue stain), mild-moderate anaemia.

Question 5

Difference between β⁺ and β⁰ thalassaemia?

Answer 5

β⁺: Reduced β-globin production.

β⁰: No β-globin production.

Question 6

Why do β-thalassaemia patients develop iron overload?

Answer 6

Chronic transfusions + increased gut iron absorption (due to ineffective erythropoiesis).

Question 7

Key blood film feature in β-thalassaemia major?

Answer 7

Target cells, nucleated RBCs, basophilic stippling.

Question 8

What triggers sickling in HbS?

Answer 8

Deoxygenation → HbS polymerisation → RBC distortion.

Question 9

Name two vaso-occlusive crises in SCD.

Answer 9

Painful crisis (bone/joint ischemia).

Acute chest syndrome (lung infarction).

Question 10

Why does sickle cell trait (HbAS) protect against malaria?

Answer 10

Parasite cannot remodel HbS-containing RBCs effectively.

Question 11

What two tests confirm SCD?

Answer 11

Sickle solubility test (turbid = HbS).

HPLC/electrophoresis (quantifies Hb variants).

Question 12

How does Hb electrophoresis at acid pH differentiate HbS from HbC?

Answer 12

HbS migrates differently due to charge differences.