Beta Thalassemia Intermedia

Beta thalassaemia intermedia is a clinically heterogeneous form with anaemia of lower severity that does not require regular transfusion from early childhood.

Genotypes: mild beta chain mutations, homozygous or compound heterozygous, coinheritance of alpha thalassaemia, persistent HbF (Xmn1), triplicated alpha genes with beta trait (dominant).

Haemoglobin 7 to 10 g/dL at baseline.

Chronic hypoxia and ineffective erythropoiesis drive extramedullary haematopoiesis and increased iron absorption.

Complications: iron overload (non transfusional), extramedullary masses, leg ulcers, thrombosis, pulmonary hypertension, gallstones, osteoporosis.

• Presents later (2 to 6 years): pallor, mild jaundice, splenomegaly, growth retardation.
• Skeletal changes, bone pain, paraspinal masses with cord compression.
• Leg ulcers, priapism, thrombotic events (especially after splenectomy).
• Progressive iron overload.

• Microcytic hypochromic anaemia, raised HbF and HbA2 on electrophoresis.
• Genotyping for beta and alpha gene mutations.
• Ferritin and liver iron concentration by MRI (non transfusional overload), cardiac T2*, echocardiography for pulmonary pressure.
• Bone density, ultrasound for gallstones, spinal MRI for masses.

• Transfusion on demand (infections, pregnancy, surgery, growth failure, cardiac or bone complications), or regular if progressive.
• Iron chelation guided by liver iron concentration over 5 mg/g dry weight: deferasirox 10 to 20 mg/kg daily (lower dose threshold for non transfusion dependent patients), deferiprone.
• Hydroxyurea 10 to 20 mg/kg daily to increase HbF (response in about 60%), reduces extramedullary masses; luspatercept 1 to 1.25 mg/kg every 3 weeks.
• Splenectomy for symptomatic hypersplenism (increases thrombosis risk; thromboprophylaxis with aspirin 75 to 100 mg).
• Thromboprophylaxis (aspirin or low molecular weight heparin) in high risk situations.
• Folic acid 5 mg daily, calcium, vitamin D, bisphosphonates for osteopenia.
• Extramedullary masses: hypertransfusion, radiotherapy, hydroxyurea; surgery for cord compression.
• Gene therapy and transplantation for selected severe cases.