Haemoglobinopathies

🧬 Background on Haemoglobin

• Structure: Haemoglobin (Hb) is a tetrameric protein in red blood cells consisting of 2 α and 2 non-α globin chains (β, δ, or γ), each bound to a haem group with iron (Fe²⁺) for O₂ binding.
• Normal Adult Hb:
  • HbA (α₂β₂) → ~95–98%.
  • HbA₂ (α₂δ₂) → ~2–3%.
  • HbF (α₂γ₂) → <1% (higher in neonates 👶).
• Switching: HbF predominates in utero (better O₂ affinity), gradually replaced by HbA postnatally. Failure of correct switching or mutations in globin chains → haemoglobinopathies.
• Pathophysiology: Point mutations (e.g. HbS, HbC, HbE) or reduced globin synthesis (thalassaemias) → impaired O₂ delivery, haemolysis, anaemia, and end-organ damage.
• Global Impact 🌍: Haemoglobinopathies are among the most common inherited disorders worldwide, especially in Africa, the Mediterranean, the Middle East, India, and SE Asia (due to malaria protection advantage).

🩸 Sickle Cell Disease (SCD)

• Clinical Features: Chronic haemolytic anaemia, vaso-occlusive crises 🔥 (painful episodes), acute chest syndrome 🫁, splenic sequestration (children), functional asplenia → infections 🦠, jaundice, delayed growth 🚸.
• Complications: Stroke ⚡, priapism 🍆, leg ulcers, gallstones, renal impairment, pulmonary hypertension, chronic pain.
• Investigations: FBC (normocytic anaemia, ↑ reticulocytes), blood film (sickle cells, Howell–Jolly bodies), haemoglobin electrophoresis (↑ HbS), sickle solubility test.
• Treatment:
  • 💊 Hydroxyurea → ↑ HbF, ↓ crises.
  • 💉 Regular blood transfusions → prevent stroke/complications; watch iron overload.
  • 🛡️ Vaccinations (pneumococcal, meningococcal, Hib) + lifelong penicillin prophylaxis (children).
  • ⚡ Pain crises: hydration, oxygen, analgesia (NSAIDs/opioids).
  • 🧬 Curative: allogeneic stem cell transplant in selected cases.

🩸 Thalassaemia Major (β-Thalassaemia Major / Cooley’s Anaemia)

• Clinical Features: Severe anaemia, failure to thrive 🚼, hepatosplenomegaly, jaundice, bone deformities 🦴 (frontal bossing, “hair-on-end” skull), extramedullary haematopoiesis.
• Investigations: FBC (microcytic anaemia, target cells), haemoglobin electrophoresis (↑ HbF, ↑ HbA2, absent/↓ HbA), genetic testing 🧬.
• Treatment:
  • 🩸 Lifelong transfusion programme.
  • 💊 Iron chelation (deferoxamine, deferasirox) → prevent iron overload.
  • 🌱 Folic acid supplementation.
  • 🫀 Monitor for cardiac, hepatic, and endocrine complications (iron deposition).
  • 🧬 Bone marrow / stem cell transplant = only curative option.

🩸 Haemoglobin C Disease

• Clinical Features: Mild–moderate haemolytic anaemia, splenomegaly, intermittent joint pain 🤕, gallstones.
• Investigations: FBC + blood film (HbC crystals), haemoglobin electrophoresis (↑ HbC).
• Treatment: Often supportive only → folic acid, hydration, analgesia for pain; transfusion rarely needed.

🩸 Haemoglobin E Disease

• Clinical Features: Usually asymptomatic 🙂 or mild anaemia; mild splenomegaly possible.
• Investigations: Hb electrophoresis confirms diagnosis.
• Treatment: Generally none required; monitor for anaemia. Rare severe cases may need transfusion (esp. HbE/β-thalassaemia compound heterozygotes).

🩸 Beta-Thalassaemia Intermedia

• Clinical Features: Anaemia (mild–moderate), bone deformities 🦴, delayed growth 🚸, splenomegaly; usually less severe than major but may still cause morbidity.
• Investigations: Hb electrophoresis (↑ HbF, variable HbA2), genetic testing 🧬.
• Treatment: Occasional transfusions, folic acid, iron chelation if overload develops, splenectomy in selected patients, stem cell transplant if severe.

📚 Teaching Pearls

💡 Key exam tips: – Sickle cell → painful crises, acute chest, stroke, “autosplenectomy” → infections. – Thalassaemia major → transfusion dependent, “hair-on-end” skull, iron overload. – HbC → mild disease with HbC crystals. – HbE → common in SE Asia, usually mild but severe if combined with β-thalassaemia. – Hb electrophoresis = gold standard for diagnosis.