Thalassaemia major: transfusion and iron overload

01Purpose and principlesWhat the treatment does and how it fits into care.

In severe beta-globin deficiency, unmatched alpha chains precipitate inside erythroblasts, causing intramedullary death and chronic anaemia. Unchecked erythropoietin drives marrow expansion, skeletal change, splenomegaly and extramedullary masses. A regular transfusion programme supplies functional erythrocytes and suppresses this expansion. The dose is prescribed from patient weight, unit haematocrit, haemoglobin trajectory and symptoms. A consistently falling pre-transfusion value prompts review of interval, unit volume, bleeding, hypersplenism, antibodies and haemolysis rather than automatic extra units.

Transfused erythrocytes contribute roughly 200–250 mg iron per adult unit. Once transferrin becomes saturated, non-transferrin-bound iron enters tissues and catalyses oxidative injury. The liver accumulates the largest store, while myocardial iron causes arrhythmia and cardiomyopathy and endocrine deposition impairs growth, puberty, glucose, thyroid, parathyroid and fertility. Serum ferritin cannot map this distribution. Specialist MRI quantifies liver iron and cardiac T2-star, while echocardiography, ECG and endocrine tests measure consequences.

Chelation is a long-term dose-matching exercise. Intake from transfusion is balanced against drug removal, and intensity changes when cardiac or liver burden changes. Combination treatment can be used for severe or discordant organ loading under a specialist centre. Adherence should be discussed through formulation, timing, adverse effects, school or work and mental health rather than moral labels. Curative allogeneic transplantation is an option for selected patients; gene-addition or gene-editing therapies follow current commissioning and long-term surveillance and do not remove pre-existing iron injury immediately.

Key points

Transfusion-dependent beta-thalassaemia requires regular red cells to sustain growth, activity and organ oxygenation and suppress harmful marrow expansion and extramedullary haematopoiesis.
Before the first elective transfusion, record an extended red-cell phenotype or genotype and antibody screen; use leucocyte-depleted, appropriately antigen-matched units through the specialist programme.
Pre-transfusion haemoglobin targets and intervals are individualised, commonly maintaining about 90–105 g/L, with higher targets for selected cardiac or extramedullary indications.
Each red-cell unit delivers iron that the body cannot actively excrete, so chronic transfusion inevitably requires a measured iron-removal strategy unless definitive cure intervenes.
Ferritin is useful as a trend but changes with infection, inflammation, liver injury and ascorbate; liver iron concentration by validated MRI better quantifies storage burden.
Cardiac T2-star MRI identifies myocardial iron before symptoms and guides chelator intensity; normal liver iron does not guarantee a normal heart in every patient.
Chelator selection considers liver and cardiac iron, transfusion rate, renal and liver function, age, pregnancy, adverse effects, lifestyle and likely adherence.
Deferasirox is oral and requires renal, hepatic and gastrointestinal monitoring; deferiprone penetrates cardiac iron well but requires strict neutrophil surveillance.
Desferrioxamine is administered subcutaneously or intravenously and remains important for severe cardiac loading, but infusion burden, auditory and ocular toxicity affect use.
Long-term care includes annual or risk-based endocrine, bone, liver, cardiac, viral, fertility and psychosocial assessment, plus early discussion of transplantation or advanced therapies where appropriate.

02Indications, selection and cautionsWho may benefit, who needs urgent treatment and important alternatives.

Under-transfusion phenotype

Fatigue, growth failure, bone expansion, increasing spleen size or extramedullary masses suggest inadequate suppression after adherence and haemolysis are reviewed.

Hepatic iron burden

Rising liver iron, fibrosis markers or transaminases indicates storage injury, but viral, metabolic and medicine causes must be assessed concurrently.

Cardiac siderosis

Reduced exercise, palpitations, ventricular dysfunction or falling cardiac T2-star can precede overt iron cardiomyopathy and demands intensified specialist treatment.

Chelator emergencyRed flag

Fever or painful throat while taking deferiprone requires stopping the drug and obtaining an urgent neutrophil count.

Delayed transfusion reaction

Jaundice, dark urine, pain or a haemoglobin fall after transfusion warrants haemolysis and antibody investigation even when the current screen is negative.

03Assessment before treatmentTests and checks that guide safe selection.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Pre-transfusion full count and antibody screenFirst step
Why
Guide dose and detect new compatibility risk.
Interpretation and limitations
Interpret haemoglobin against interval and target; preserve historical antibodies permanently because titres can fall below detection.
02
Extended red-cell genotype
Why
Support durable antigen matching in a repeatedly transfused patient.
Interpretation and limitations
Genotyping avoids mixed-field limitations after recent transfusion and helps resolve variant Rh or difficult serology.
03
Serial serum ferritin
Why
Track broad iron direction between imaging assessments.
Interpretation and limitations
Use repeated values with transfusion input, inflammation and liver status; an isolated result should not drive major chelator escalation.
04
Liver iron MRI
Why
Quantify hepatic tissue iron non-invasively.
Interpretation and limitations
Validated concentration estimates guide chelation intensity and trend; different platforms require consistent specialist interpretation.
05
Cardiac T2-star MRI
Why
Detect and grade myocardial iron before failure.
Interpretation and limitations
Shorter T2-star indicates greater loading; result and ventricular function determine urgency, combination chelation and scan interval.
06
ECG, echocardiography and exercise review
Why
Identify functional cardiac consequences and non-iron disease.
Interpretation and limitations
Normal ejection fraction does not exclude early myocardial iron, while dysfunction with normal T2-star prompts alternative cardiomyopathy assessment.
07
Endocrine and bone panel
Why
Detect iron-related or treatment-related organ injury.
Interpretation and limitations
Growth, puberty, glucose, thyroid, calcium, vitamin D, gonadal function and bone density are selected by age and clinical risk.

04Treatment approachPreparation, options, escalation and aftercare.

01Regular transfusionSuppress ineffective erythropoiesis safelyFirst stepA patient meets specialist criteria for transfusion-dependent thalassaemia care.

1Record genotype, extended red-cell antigens, antibody and reaction history and obtain baseline viral, iron and organ assessments before repeated exposure.
2Give leucocyte-depleted, appropriately antigen-matched red cells, commonly 10–15 mL/kg every 2–4 weeks, to maintain a pre-transfusion haemoglobin of about 90–105 g/L; use a higher specialist target only for a defined cardiac or extramedullary indication.
3Investigate increasing requirements through bleeding, hypersplenism, alloantibody, haemolysis, unit characteristics and adherence before altering the long-term target.

02Iron mappingMeasure tissue, not ferritin aloneTransfusion exposure accumulates or ferritin and organ features suggest iron loading.

1Calculate annual transfusion iron input and trend ferritin with CRP, liver tests and infection rather than interpreting one inflammatory value.
2Obtain validated liver iron MRI and cardiac T2-star at age- and burden-appropriate intervals, adding endocrine, cardiac and bone functional tests.
3Classify organ urgency and agree an iron target, chelator, dose and next imaging date with the patient and specialist centre.

03Chelation adjustmentMatch removal to organs and lifeIron burden rises, remains unsafe or differs between liver and heart despite treatment.

1Confirm actual dosing, formulation, timing, vomiting, interactions and adverse effects in a non-judgemental review before declaring pharmacological failure.
2Optimise single-agent dosing or use specialist combination therapy for severe cardiac or discordant loading, with intensified product-specific safety tests.
3Repeat tissue imaging at an interval appropriate to severity and reduce intensity as burden falls to avoid over-chelation and renal, hepatic, neurological or sensory toxicity.

05Regimens, contraindications and interactionsTreatment details and the circumstances that modify them.

Corrects severe anaemia, suppresses marrow expansion and prevents skeletal and extramedullary complications of transfusion-dependent thalassaemia.

Leucocyte-depleted red cells

A common maintenance prescription is 10–15 mL/kg every 2–4 weeks, adjusted to maintain pre-transfusion haemoglobin around 90–105 g/L and suppress ineffective erythropoiesis. Use appropriately antigen-matched units and calculate actual annual volume per kilogram.

Check the complete antibody and reaction history before every exposure. Alloimmunisation, delayed haemolysis, volume overload, infection and iron input require observation, haemovigilance and long-term review.

Chelates systemic iron for faecal excretion and is widely used for chronic transfusional loading.

Deferasirox

For film-coated tablets, a common starting dose with frequent transfusion is 14 mg/kg orally once daily; 7 mg/kg may suit a lower iron input and 21 mg/kg a high input needing reduction. Adjust by 3.5–7 mg/kg every 3–6 months to ferritin and MRI response, up to 28 mg/kg/day. Dispersible-tablet doses are about 30% higher and are not interchangeable.

Confirm duplicate baseline creatinine and avoid treatment when creatinine clearance is below the licensed threshold. Monitor eGFR, urine protein, liver tests, full count and gastrointestinal bleeding; interrupt for significant dehydration or organ injury and review pregnancy, interacting nephrotoxins and over-chelation risk.

Removes labile and tissue iron and can be valuable in myocardial siderosis.

Deferiprone

Give 25 mg/kg orally 3 times daily, usually 75 mg/kg/day; do not exceed 100 mg/kg/day. A specialist may use it alone or in combination when cardiac or total iron requires intensified removal.

Monitor the absolute neutrophil count weekly for the first year; after an uninterrupted stable year, a specialist may extend this to the 2–4-week transfusion interval. Stop immediately for fever, sore throat or mouth ulcers and obtain an urgent count. Do not re-challenge after agranulocytosis; also monitor liver enzymes, arthropathy and zinc and avoid pregnancy.

Provides potent parenteral chelation and may be combined with an oral agent for urgent organ iron removal.

Desferrioxamine

A common chronic regimen is 20–40 mg/kg by subcutaneous infusion over 8–12 hours on 5–7 days each week. Severe myocardial siderosis may require specialist continuous intravenous treatment or combination chelation.

Infusion-site reactions, growth effects and retinal, auditory, pulmonary, renal or neurological toxicity require dose-ratio and specialist monitoring. Withhold during serious infection, particularly suspected Yersinia or mucormycosis, and reduce intensity as iron burden falls.

06Complications, monitoring and follow-upAdverse effects, response and longer-term review.

At every transfusion record pre- and post-transfusion haemoglobin where indicated, unit exposure, antibody screen, reaction and actual interval.
Review annual transfusion volume per kilogram because rising requirements can reveal hypersplenism, haemolysis or programme drift.
Trend ferritin frequently but anchor major chelation decisions to validated liver and cardiac MRI and organ function.
Apply chelator-specific full-count, renal, liver, urine, auditory, visual and growth monitoring with clear temporary stopping rules.
Screen glucose, thyroid, parathyroid, gonadal, growth, bone, liver, cardiac and viral health at age- and risk-based intervals.
Revisit adherence, treatment burden, fertility, pregnancy, mental health, transition and curative-therapy preferences as circumstances evolve.

07Special situationsVariants, exceptions and circumstances that change the usual approach.

Ferritin is a direction

It helps show trend but cannot locate iron or reliably distinguish myocardial from hepatic burden during inflammation.

Heart and liver diverge

Different uptake and chelator penetration mean reassuring liver iron does not always exclude dangerous myocardial siderosis.

Transfusion prevents damage

Regular red cells do more than correct fatigue; they suppress erythropoietin-driven marrow expansion and extramedullary haematopoiesis.

Adherence is a design problem

Formulation, infusion time, side effects, privacy and daily routine should shape a feasible plan before dose escalation.

08Common pitfallsFrequent interpretation and management errors.

01
Escalating chelation from one ferritin result.
02
Assuming low liver iron guarantees a safe heart.
03
Losing historical antibodies after a negative screen.
04
Continuing deferiprone during fever without an urgent count.
05
Treating poor adherence as character failure.
06
Over-transfusing without reviewing viscosity and programme target.