PA16.1-3 | Sickle Cell Disease & Thalassaemia — Hereditary Haemolytic Anaemias — Summary & Reflection

REFLECT

You have now covered the two major hereditary haemolytic anaemias. Before moving on, take 3 minutes to sketch a comparison table from memory:

If any cell is blank, revisit the corresponding content block. The ability to fill this table from memory is the minimum standard for the PA16.2 exam question.

KEY TAKEAWAYS

Cluster H5, SDL 2 — Hereditary Haemolytic Anaemias: Key Takeaways

Sickle Cell Disease (HbSS):
- Caused by β6 Glu→Val point mutation → HbS polymerisation on deoxygenation → sickling → vaso-occlusion + haemolysis
- Smear: sickle cells, target cells, Howell-Jolly bodies (post-autosplenectomy), nucleated RBCs — normocytic
- Diagnosis: positive solubility test (screen) + Hb electrophoresis/HPLC (definitive)
- Trait (HbAS) is clinically silent; only disease (HbSS) manifests crises

β-Thalassaemia Major:
- Deficient β-chain → unpaired α-chains → inclusion bodies → ineffective erythropoiesis + peripheral haemolysis
- Smear: microcytic hypochromic, target cells, basophilic stippling, nucleated RBCs
- Complications: bone marrow expansion (rodent facies), massive hepatosplenomegaly, secondary haemosiderosis
- Diagnosis: Hb electrophoresis — β-thal major: ↑↑ HbF, no HbA; β-thal minor: ↑ HbA2 (>3.5 %)

Other hereditary categories:
- Membrane defects: hereditary spherocytosis (microspherocytes, ↑ osmotic fragility, Coombs negative)
- Enzyme defects: G6PD deficiency (Heinz bodies + bite cells; triggered by oxidant stress)

Diagnostic discriminators to memorise:
- SCD vs β-thal: MCV normal in SCD, low in thal
- β-thal trait vs IDA: ferritin normal + HbA2 ↑ in thal; ferritin low + HbA2 normal in IDA
- AIHA vs G6PD: Coombs positive in AIHA, negative in G6PD deficiency