Haematology & Oncology

Thalassaemia

Thalassaemia is an inherited disorder of reduced alpha- or beta-globin synthesis causing ineffective erythropoiesis, haemolysis and microcytic anaemia; severity ranges from an asymptomatic carrier state to transfusion-dependent disease with lifelong risk from iron overload.

In a nutshell

Thalassaemia is inherited reduced globin synthesis causing microcytic anaemia from ineffective erythropoiesis and haemolysis. Trait usually needs no treatment; transfusion-dependent disease needs a specialist red-cell programme plus lifelong iron-burden surveillance and chelation. Iron-related cardiac, liver, endocrine and bone disease are preventable targets of care.

Classic presentation

A child develops pallor, jaundice, failure to thrive and hepatosplenomegaly as clinically significant beta-thalassaemia emerges, or an otherwise well person is found to have marked microcytosis with little anaemia and a normal iron store.

Key points

A low mean cell volume is not synonymous with iron deficiency: check ferritin and haemoglobin analysis before prescribing iron.
Alpha-thalassaemia may require molecular testing because routine haemoglobin analysis can be non-diagnostic.
Transfusion-dependent disease requires safe regular red-cell transfusion and active iron-overload prevention.
Ferritin alone cannot describe tissue iron; liver and cardiac MRI are important parts of specialist surveillance.
Iron chelators have important renal, hepatic, auditory, ocular and haematological toxicities that require BNF-guided monitoring.
NICE exagamglogene autotemcel is a managed-access specialist option for selected older children and adults; it does not remove the need for specialist haemoglobinopathy care.

First-line investigation

Full blood count, reticulocytes, blood film, ferritin and haemoglobin analysis, followed by targeted globin-gene testing and specialist iron-burden assessment.

Management

Treat acute deterioration as a haemoglobinopathy emergency

Escalate severe symptomatic anaemia, fever or suspected sepsis, acute haemolysis, aplastic crisis, cardiac decompensation or transfusion reaction to the thalassaemia and transfusion teams; stop a suspected transfusion reaction and follow the local reaction pathway.^1,4

Confirm the phenotype and quantify risk

Use FBC, reticulocytes, film, ferritin, haemolysis markers and haemoglobin analysis; use globin-gene testing when alpha-thalassaemia or a complex variant is not resolved by routine testing.^1,2
Establish whether the person is transfusion-dependent, non-transfusion-dependent or a carrier, and assess liver and cardiac iron with validated MRI-based methods rather than relying on ferritin alone.^1,3,6

Deliver the core specialist treatment

Use a thalassaemia-centre red-cell transfusion programme for transfusion-dependent disease, with the centre's pre-transfusion haemoglobin target, interval, volume, compatibility and antibody-monitoring plan.^1,2,4
Start or adjust chelation when the specialist assessment shows clinically important iron burden or risk, using deferasirox, deferiprone or desferrioxamine with BNF-guided toxicity and adherence monitoring.^3,6,8

Prevent organ failure and discuss curative options

Escalate cardiac symptoms, rising cardiac iron, liver disease, endocrine failure, pulmonary hypertension, bone disease or fertility problems to the relevant MDT while continuing the haemoglobinopathy plan.^1,3
Assess for HSCT early when suitable; NICE recommends exagamglogene autotemcel with managed access for people aged 12 years and over with transfusion-dependent beta-thalassaemia when HSCT is suitable but a matched related donor is unavailable.^9,1,2

Build lifelong preventive care

Review iron, heart, liver, endocrine, bone, renal, growth, puberty, fertility, vaccination, dental, psychological and transition needs at the specialist centre; provide a written emergency and transfusion-reaction plan.^1,3,4
For pregnancy or an at-risk couple, arrange preconception haematology-obstetric review, partner testing, genetic counselling and prenatal diagnostic options through the current NHS screening pathway.^5,7,1

Exam traps

Microcytosis with a relatively preserved red-cell count suggests thalassaemia trait but still needs ferritin and haemoglobinopathy assessment.
A normal electrophoresis does not reliably exclude alpha-thalassaemia.
A transfusion-dependent patient can have a reassuring haemoglobin while accumulating dangerous cardiac or hepatic iron.
Non-transfusion-dependent thalassaemia can still cause iron overload through increased absorption.
Fever, acute anaemia or a suspected transfusion reaction needs urgent specialist action; do not manage it as uncomplicated chronic anaemia.

Illustrations

Blood film in thalassaemiaA blood film showing microcytic hypochromic red cells with target cells and, in major disease, nucleated red cells and basophilic stippling.Dr Graham Beards, Wikimedia Commons · CC-BY-SA-4.0

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.