Red Flags
- Heart failure with iron overload (cardiac T2* <10 ms or LVEF <50%) — emergency cardiology + intensive chelation (combined deferiprone + deferoxamine)[1]
- Severe transfusion reaction (haemolytic, anaphylactic, TRALI, TACO) — stop transfusion, supportive care, reporting; investigate alloimmunisation[1]
- Pregnancy with thalassaemia — multidisciplinary preconception (cardiac and endocrine optimisation, switch deferoxamine, fetal medicine)[1]
- New endocrine deficit (hypothyroidism, diabetes, adrenal, gonadal) on chelation regimen — replacement therapy and chelation review[1]
First-line treatment
Interventions
- Regular transfusion programme (transfusion-dependent disease)[1]Pre-transfusion Hb target 9–10.5 g/dL (Hb 12 g/dL post-transfusion); leukoreduced, extended-antigen matched red cells; usual interval 2–4 weeks; phenotype matching from start to reduce alloimmunisation
- Iron chelation when ferritin >1000 ng/mL or post-20 transfusions[1]Oral deferasirox first-line in most patients; subcutaneous deferoxamine for severe iron overload or pregnancy; combined deferasirox + deferiprone or deferoxamine + deferiprone for severe cardiac iron
- Disease-modifying therapy[1]Hydroxyurea in selected non-transfusion-dependent thalassaemia raises HbF; luspatercept reduces transfusion need in adults with regular transfusion requirement
- Curative — haematopoietic stem cell transplant or gene therapy[1]Matched sibling donor HSCT — best outcomes when transplanted before significant organ damage; matched unrelated/haploidentical donors with conditioning; gene therapy (betibeglogene autotemcel, exagamglogene autotemcel) for selected severe disease where access permits
- Carrier screening and genetic counselling[1]All adults of reproductive age in high-prevalence regions; antenatal couple screening; prenatal diagnosis (chorionic villus sampling, amniocentesis) for at-risk couples; selective termination per local framework
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Deferasirox[1] | Oral iron chelator | 20–40 mg/kg PO daily film-coated tablet; 14–28 mg/kg/day oral granules | Children ≥2 years 20–30 mg/kg/day | First-line in transfusion-dependent disease; monthly creatinine, LFT, urinalysis; rare hepatic, renal, gastrointestinal, ophthalmic, auditory adverse events |
| Deferoxamine (subcutaneous)[1] | Parenteral iron chelator | 30–50 mg/kg SC infusion over 8–12 h, 5–7 nights/week | 20–40 mg/kg/day in children | Used in severe iron overload, pregnancy, deferasirox intolerance; growth delay in children; ophthalmic and auditory monitoring; injection-site reactions reduce adherence |
| Deferiprone[1] | Oral iron chelator | 75–100 mg/kg/day PO in 3 divided doses | Children ≥6 years per local label | Cardiac iron preferred (penetrates myocardium); weekly FBC for agranulocytosis; combined with deferasirox or deferoxamine for cardiac iron overload |
| Luspatercept[1] | Erythroid maturation agent | 1 mg/kg SC every 3 weeks; titrate to 1.25 mg/kg | — | Adults with transfusion-dependent thalassaemia requiring regular transfusion; reduces transfusion frequency; thrombosis risk; access varies |
| Hydroxyurea (selected non-transfusion-dependent)[1] | Ribonucleotide reductase inhibitor / fetal Hb inducer | 10–20 mg/kg/day PO; titrate by FBC | Same weight-based dosing | Selected non-transfusion-dependent thalassaemia and intermedia; raises HbF; teratogenicity; reversible cytopenia |
Deferasirox[1]
Oral iron chelator
- Adult
- 20–40 mg/kg PO daily film-coated tablet; 14–28 mg/kg/day oral granules
- Paediatric
- Children ≥2 years 20–30 mg/kg/day
First-line in transfusion-dependent disease; monthly creatinine, LFT, urinalysis; rare hepatic, renal, gastrointestinal, ophthalmic, auditory adverse events
Deferoxamine (subcutaneous)[1]
Parenteral iron chelator
- Adult
- 30–50 mg/kg SC infusion over 8–12 h, 5–7 nights/week
- Paediatric
- 20–40 mg/kg/day in children
Used in severe iron overload, pregnancy, deferasirox intolerance; growth delay in children; ophthalmic and auditory monitoring; injection-site reactions reduce adherence
Deferiprone[1]
Oral iron chelator
- Adult
- 75–100 mg/kg/day PO in 3 divided doses
- Paediatric
- Children ≥6 years per local label
Cardiac iron preferred (penetrates myocardium); weekly FBC for agranulocytosis; combined with deferasirox or deferoxamine for cardiac iron overload
Luspatercept[1]
Erythroid maturation agent
- Adult
- 1 mg/kg SC every 3 weeks; titrate to 1.25 mg/kg
- Paediatric
- —
Adults with transfusion-dependent thalassaemia requiring regular transfusion; reduces transfusion frequency; thrombosis risk; access varies
Hydroxyurea (selected non-transfusion-dependent)[1]
Ribonucleotide reductase inhibitor / fetal Hb inducer
- Adult
- 10–20 mg/kg/day PO; titrate by FBC
- Paediatric
- Same weight-based dosing
Selected non-transfusion-dependent thalassaemia and intermedia; raises HbF; teratogenicity; reversible cytopenia
Safety-net
- Take iron chelator every day as prescribed and attend monitoring — undetected iron overload causes silent cardiac, hepatic, and endocrine damage[1]
- Plan pregnancy with your haematologist — switch deferasirox/deferiprone to deferoxamine ≥3 months pre-conception; cardiac and endocrine optimisation[1]
- Report new chest discomfort, breathlessness, palpitations, or weight gain — could signal cardiac iron overload requiring urgent intensification of chelation[1]
Referral criteria
- All confirmed thalassaemia major / intermediaHaematology service for transfusion programme, chelation, and surveillance[1]
- Severe cardiac iron overload (T2* <10 ms or HF)Cardiology and haematology with intensive chelation[1]
- Eligibility for HSCT or gene therapyTertiary haematology / BMT centre[1]
- Pregnancy with thalassaemia or carrier statusJoint haematology, obstetric, and antenatal genetics clinic[1]
Clinical summary
Diagnosis, transfusion, iron chelation, and curative pathway for beta thalassaemia major and intermedia in adults and children.