Haemoglobinopathies are inherited disorders affecting the structure or production of haemoglobin. These conditions are important to recognise and manage effectively for the UKMLA.

Types of Haemoglobinopathies:

1. Structural Haemoglobinopathies:

• Sickle Cell Disease (SCD):
  • Mutation in the HBB gene leads to haemoglobin S (HbS), causing red cell sickling.
  • Key Complications: Vaso-occlusive crises, acute chest syndrome, stroke, and splenic sequestration.
  • Management: Hydroxycarbamide, blood transfusions, pain relief, and infection prevention.
• Haemoglobin C Disease:
  • Mutation in the HBB gene, leading to HbC.
  • Milder haemolytic anaemia than SCD.
  • Management: Supportive care, rarely requires transfusions.

2. Thalassaemias:

• Alpha Thalassaemia:
  • Reduced or absent alpha-globin chain production.
  • Types:
    • Silent Carrier: One gene deletion; asymptomatic.
    • Alpha-Thalassaemia Trait: Two gene deletions; mild microcytic anaemia.
    • Haemoglobin H Disease: Three gene deletions; moderate haemolysis, splenomegaly.
    • Hydrops Fetalis: Four gene deletions; incompatible with life.
  • Management: Supportive care, folic acid, transfusions in severe cases.
• Beta Thalassaemia:
  • Reduced or absent beta-globin chain production.
  • Types:
    • Beta-Thalassaemia Minor: Heterozygous; mild microcytic anaemia.
    • Beta-Thalassaemia Intermedia: Variable severity.
    • Beta-Thalassaemia Major (Cooley’s Anaemia): Severe anaemia, transfusion-dependent, complications from iron overload.
  • Management: Regular transfusions, iron chelation, and curative bone marrow transplant in selected cases.

3. Other Haemoglobinopathies:

• Haemoglobin E:
  • Common in Southeast Asia.
  • Mild microcytic anaemia; usually asymptomatic.

Pathophysiology:

1. Structural Defects:
   • Altered haemoglobin structure causes red cell deformation, haemolysis, and vaso-occlusion.
2. Production Defects:
   • Imbalanced globin chain production leads to ineffective erythropoiesis and chronic haemolysis.

Clinical Features:

1. General Symptoms:
   • Fatigue, pallor, dyspnoea.
2. Complications:
   • Anaemia: Microcytic or haemolytic.
   • Splenomegaly: Common in thalassaemias.
   • Growth delay and bone deformities (e.g., “chipmunk facies” in beta-thalassaemia major).

Investigations:

1. Full Blood Count (FBC):
   • Microcytosis (low MCV), hypochromia (low MCH).
   • Target cells on blood film.
2. Haemoglobin Electrophoresis:
   • Identifies abnormal haemoglobins (e.g., HbS, HbC, HbE).
3. Genetic Testing:
   • Confirms diagnosis and helps with prenatal counselling.
4. Iron Studies:
   • Distinguish thalassaemia from iron deficiency anaemia.

Management:

General Principles:

• Regular follow-up and monitoring of haemoglobin levels.
• Folic acid supplementation for haemolysis-related anaemia.

Specific Treatments:

1. Sickle Cell Disease:
   • Hydroxycarbamide: Increases HbF production.
   • Blood transfusions: For severe anaemia or complications.
   • Prophylactic penicillin and vaccinations for infection prevention.
2. Beta-Thalassaemia Major:
   • Regular transfusions to maintain Hb > 90 g/L.
   • Iron chelation (e.g., deferasirox) to prevent iron overload.
   • Bone marrow transplantation: Potentially curative in selected patients.
3. Alpha Thalassaemia:
   • Haemoglobin H Disease: Supportive care, transfusions if needed.
   • Hydrops Fetalis: Requires prenatal diagnosis and counselling.

Complications:

1. Iron Overload:
   • Secondary to transfusions in thalassaemia major; leads to organ damage.
2. Infection:
   • Increased risk in splenectomised patients and sickle cell disease.
3. Stroke and Vaso-Occlusion:
   • Seen in sickle cell disease.

Prognosis:

• Varies depending on type and severity:
  • Mild forms (e.g., beta-thalassaemia minor): Excellent prognosis.
  • Severe forms (e.g., beta-thalassaemia major, SCD): Require intensive management.

Key Exam Points for UKMLA:

1. Diagnosis:
   • Use haemoglobin electrophoresis for identification.
2. Differentials:
   • Differentiate microcytic anaemia types (thalassaemia vs. iron deficiency).
3. Management:
   • Hydroxycarbamide for SCD; transfusion and chelation for thalassaemia major.
4. Screening:
   • Family screening and prenatal testing for at-risk populations.
5. Complications:
   • Know how to prevent and manage iron overload, infection, and stroke.