Thalassaemia syndromes

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Target exams

Red flags

• A child with beta-thalassaemia major presenting at six to twelve months with severe microcytic anaemia, failure to thrive and hepatosplenomegaly as the fetal haemoglobin falls needs urgent confirmation by haemoglobin separation and commencement of a regular transfusion programme
• A falling cardiac T2 star of under 10 milliseconds on magnetic resonance imaging marks severe myocardial iron loading and a high short-term risk of heart failure, the leading cause of death in thalassaemia major
• A child on deferiprone who develops fever and a neutrophil count under 0.5 times ten to the nine per litre has drug-induced agranulocytosis, an emergency that demands immediate cessation of the drug and broad-spectrum antibiotics
• A four-gene alpha-thalassaemia deletion produces Hb Bart hydrops fetalis, a condition incompatible with postnatal life without intrauterine transfusion, and a leading cause of perinatal mortality in South-East Asia
• A transfusion-dependent adolescent who is short, delayed in puberty and glucose intolerant has endocrine iron overload of the anterior pituitary and pancreas, and needs hormone and endocrine surveillance

Life stages

Care settings

Clinical exam formats

Board mappings

• Recognises beta-thalassaemia major as the autosomal recessive disorder of beta-globin synthesis presenting at six to twelve months with severe microcytic anaemia, failure to thrive and hepatosplenomegaly
• States the regular transfusion target of a pre-transfusion haemoglobin of 90 to 100 g per litre and names deferasirox at 20 mg per kg per day as the first-line oral iron chelator
• Names the alpha-thalassaemia gene-deletion ladder from silent carrier through trait and haemoglobin H disease to Hb Bart hydrops fetalis
• Explains how unbalanced alpha-chain excess causes ineffective erythropoiesis and chronic haemolysis, and how transfusional and absorbed iron loads the liver, heart and endocrine glands
• Coordinates the transfusion, chelation and monitoring programme with cardiac T2 star magnetic resonance imaging, and appraises allogeneic transplant against betibeglogene gene therapy
• Appraises the BELIEVE luspatercept trial and the deferasirox and deferoxamine chelation evidence of Cappellini, Piga, Borgna-Pignatti and Modell
• Regular leucodepleted transfusion keeps the pre-transfusion haemoglobin at 90 to 100 g per litre, given every two to five weeks
• Deferasirox starts at 20 mg per kg per day orally once daily and chelation begins once the ferritin exceeds 1000 micrograms per litre
• A cardiac T2 star under 10 milliseconds marks severe myocardial iron loading and a high risk of heart failure
• Counsels the family of a newly diagnosed infant on the inheritance, the lifelong transfusion and chelation burden, and the reproductive and curative options
• Builds the multidisciplinary plan that runs haematology, transfusion, chelation, endocrine, cardiac and transition care together
• Synthesises the transfusion-dependent adolescent with iron overload, delayed puberty and glucose intolerance into an endocrine and chelation strategy
• Level 1: Recognition of the severe microcytic anaemia of beta-thalassaemia major and initiation of the transfusion programme
• Level 2: Application of iron chelation and surveillance of iron load by ferritin and cardiac T2 star magnetic resonance imaging
• Level 3: Coordination of curative therapy, endocrine and cardiac late-effects management, and transition to adult care
• The genetics of the HBB and HBA gene clusters, the beta-zero and beta-plus alleles, and the four alpha-gene deletion ladder
• The haemoglobin electrophoresis pattern of a raised haemoglobin F and the transfusion and chelation doses
• The T2 star thresholds, the BELIEVE luspatercept evidence, and the betibeglogene autotemcel gene therapy data
• Communication of the diagnosis, the inheritance, and the lifelong transfusion and chelation plan to the family
• Structured assessment of the transfused child for growth, puberty, splenomegaly, pallor and endocrine and cardiac signs
• Recognition and counselling around the iron-overload and curative-therapy pathway
• Beta-thalassaemia major as an autosomal recessive disorder of beta-globin synthesis diagnosed by haemoglobin electrophoresis with a raised haemoglobin F
• Regular transfusion, iron chelation and iron-overload monitoring as the pillars of care
• Allogeneic haematopoietic stem cell transplant and betibeglogene autotemcel gene therapy as the curative options
• Recognition of the six-to-twelve-month presentation of beta-thalassaemia major and the urgency of starting a transfusion programme
• Application of iron chelation and cardiac T2 star surveillance from the second year of life
• Coordination of the multidisciplinary thalassaemia team and the transition to adult care
• Canadian approach to carrier screening, prenatal diagnosis and newborn identification of the thalassaemia syndromes
• Regular transfusion, iron chelation and cardiac T2 star iron surveillance
• Curative transplant and gene therapy and the long-term management of endocrine and cardiac late effects