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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Microcytic hypochromic anaemia with NORMAL or raised ferritin — key distinction from iron deficiency
- Beta-thalassaemia: autosomal recessive. Trait (minor) = mild microcytosis, no treatment needed. Major = transfusion-dependent from infancy
- Alpha-thalassaemia: gene deletions. 1-2 deletions = carrier/trait; 3 deletions = HbH disease; 4 deletions = Bart's hydrops fetalis (incompatible with life)
- Haemoglobin electrophoresis is diagnostic: raised HbA2 (>3.5%) in beta-thal trait, raised HbF in beta-thal major
- Management of thalassaemia major: regular transfusions (aim Hb >90 g/L) + iron chelation (deferasirox or desferrioxamine) to prevent iron overload. Bone marrow transplant is curative
Overview
Thalassaemia is a group of inherited haemoglobinopathies characterised by reduced or absent synthesis of one or more globin chains of haemoglobin. This leads to ineffective erythropoiesis, chronic haemolysis, and compensatory bone marrow expansion. Beta-thalassaemia (reduced beta-globin production) is caused by point mutations, while alpha-thalassaemia (reduced alpha-globin production) is usually caused by gene deletions. The severity is determined by the number and type of mutations: from asymptomatic carriers to transfusion-dependent disease.
Epidemiology
Beta-thalassaemia is most prevalent in Mediterranean, Middle Eastern, South Asian, and South-East Asian populations. Alpha-thalassaemia is common in South-East Asia, Africa, and the Mediterranean. In the UK, thalassaemia predominantly affects communities of these ancestries, with an estimated 1,000 patients with thalassaemia major. Beta-thalassaemia trait affects approximately 1.5% of the world's population. The UK has an antenatal and newborn screening programme for haemoglobinopathies in high-prevalence areas.
Clinical Features
Symptoms
Beta-thal trait: usually asymptomatic — incidental finding of microcytosis on FBC
Thalassaemia major: failure to thrive and progressive anaemia from 3-6 months of age (when HbF normally switches to HbA)
Fatigue, pallor, and exercise intolerance in thalassaemia intermedia
Bone pain (marrow expansion)
Recurrent infections
Symptoms of iron overload in transfusion-dependent patients (heart failure, diabetes, liver disease)
Signs
Pallor and jaundice (chronic haemolysis)
Hepatosplenomegaly (extramedullary haemopoiesis)
Skeletal deformities in poorly treated thalassaemia major: frontal bossing, maxillary hyperplasia ("chipmunk facies"), hair-on-end skull X-ray appearance
Growth retardation and delayed puberty
Signs of iron overload: bronze skin pigmentation, heart failure, hepatomegaly
Investigations
First-line
FBC and blood filmMicrocytic hypochromic anaemia. Very low MCV disproportionate to degree of anaemia (MCV often <70 fL even with mild anaemia). Film: target cells, tear-drop cells, nucleated red blood cells in major
Ferritin and iron studiesNORMAL or RAISED (key difference from iron deficiency anaemia which has low ferritin). Do not give iron for thalassaemia trait
Haemoglobin electrophoresis / HPLCDiagnostic: beta-thal trait shows raised HbA2 >3.5%. Beta-thal major shows markedly raised HbF (60-90%) with reduced/absent HbA
Second-line
Reticulocyte countRaised in thalassaemia intermedia and major (chronic haemolysis)
LDH, bilirubinRaised if significant haemolysis
Genetic testingDNA analysis for specific mutations — important for genetic counselling and prenatal diagnosis
Specialist
Cardiac MRI T2*Gold standard for assessing myocardial iron loading in transfusion-dependent patients — guides chelation intensity
Liver MRI (FerriScan)Quantifies liver iron concentration — more accurate than serum ferritin
Endocrine function testsScreening for iron overload complications: TFTs, glucose, gonadotrophins, calcium, cortisol
1
Thalassaemia trait (minor)
- No treatment required — reassure
- Do NOT prescribe iron (ferritin is normal or raised)
- Genetic counselling — partner screening recommended if both carriers of beta-thal trait, 1 in 4 risk of thalassaemia major in offspring
2
Thalassaemia major — transfusion
- Regular red cell transfusions every 2-4 weeks to maintain pre-transfusion Hb >90-100 g/L
- Extended phenotype-matched and leucodepleted blood to reduce alloimmunisation
- Suppresses ineffective erythropoiesis, prevents skeletal deformities and growth failure
3
Iron chelation (all chronically transfused patients)
- Deferasirox (oral, once daily) — most commonly used first-line chelator
- Desferrioxamine (SC infusion over 8-12 hours, 5 nights/week) — gold standard but adherence is challenging
- Deferiprone (oral) — particularly effective for cardiac iron. Can be used in combination with desferrioxamine
- Monitor ferritin, cardiac MRI T2*, liver iron regularly
4
Curative treatment
- Allogeneic haematopoietic stem cell transplant — curative, best outcomes when performed in childhood with HLA-matched sibling donor
- Gene therapy (betibeglogene autotemcel) — approved for transfusion-dependent beta-thal. One-time treatment using autologous modified stem cells
Complications
- Iron overload: The major cause of morbidity and mortality in thalassaemia major. Cardiac siderosis → heart failure and arrhythmias (leading cause of death). Also liver cirrhosis, diabetes, hypogonadism, hypothyroidism
- Alloimmunisation: Development of antibodies to transfused red cells — makes crossmatching increasingly difficult
- Osteoporosis: Common in adults due to marrow expansion, iron overload, hypogonadism
- Infections: Transfusion-transmitted (now rare in UK) and increased susceptibility post-splenectomy
- Bart's hydrops fetalis: 4-gene deletion alpha-thal — fatal in utero without intrauterine transfusion
UKMLA Exam Tips
- 1Microcytic anaemia + NORMAL ferritin = think THALASSAEMIA TRAIT, not iron deficiency. Classic exam discriminator
- 2Raised HbA2 (>3.5%) on electrophoresis = beta-thalassaemia trait
- 3Hair-on-end skull X-ray = thalassaemia major (marrow expansion) — classic radiology spot
- 4Cardiac iron overload (measured by T2* MRI) is the leading cause of death in thalassaemia major
- 5Do NOT give iron supplements for thalassaemia trait — ferritin is not low
- 6Alpha-thal trait: normal Hb electrophoresis (HbA2 not raised). Diagnosis requires genetic testing or exclusion
practicetest your knowledge on thalassaemiaApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — haematology and beyond.
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