Beta Thalassaemia Trait

Beta thalassaemia trait (beta thalassaemia minor) is the carrier state for one mutated beta globin gene (HBB on chromosome 11), with reduced beta chain production. It causes mild microcytic anaemia or normal haemoglobin with marked microcytosis, a raised HbA2, and normal life expectancy, and is important because two carriers can have a child with beta thalassaemia major.

• Prevalence is highest in the Mediterranean, the Middle East, South Asia, Southeast Asia and parts of Africa; carrier frequency is about 1 to 10 percent in many populations.
• Inheritance: autosomal recessive; two carrier parents have a 25 percent risk with each pregnancy of a child with beta thalassaemia major or intermedia, 50 percent of a carrier child, and 25 percent of an unaffected child.
• Mechanism: excess alpha chains precipitate in red cell precursors, causing ineffective erythropoiesis, mild haemolysis, and microcytic hypochromic cells.
• Compound heterozygosity with sickle haemoglobin (HbS/beta thalassaemia) or HbE (HbE/beta thalassaemia) causes clinically important disease.
• Heterozygotes are partly protected against falciparum malaria.

• Mostly asymptomatic; mild fatigue in some.
• Mild pallor, mild splenomegaly in a few, no bone deformity, no growth impairment, and no jaundice (mild unconjugated hyperbilirubinaemia may occur).
• Pregnancy may cause lower haemoglobin and need for iron or folate.
• Iron overload is rare, but it can occur if iron is given unnecessarily or when there is coexistent hereditary haemochromatosis.
• Family history of thalassaemia or transfusion dependent relatives; ancestry.
• Red flags that suggest a more severe form (intermedia or major) are hepatosplenomegaly, haemoglobin under 90 g/L, transfusion requirement, bone changes, growth failure, or gallstones in a young person.

• FBC: haemoglobin normal or mildly reduced (90 to 130 g/L), red cell count raised (over 5.0 x 10^12/L), MCV markedly low (55 to 75 fL), MCH low (under 25 pg), red cell distribution width normal or slightly raised.
• Mentzer index (MCV divided by red cell count) under 13 favours thalassaemia; Shine and Lal index also used.
• Blood film: microcytosis, hypochromia, target cells, basophilic stippling, ovalocytes.
• Iron studies: normal or high ferritin; treat concurrent iron deficiency first because iron deficiency lowers HbA2 and can hide trait.
• Haemoglobin analysis (HPLC or electrophoresis): HbA2 raised at 3.5 to 7 percent (diagnostic), HbF normal or slightly raised (1 to 5 percent in some).
• Silent forms (normal HbA2): delta beta thalassaemia, and coexisting delta gene mutations or alpha thalassaemia may normalise HbA2; DNA analysis of the beta globin gene is needed.
• Test the partner and children when appropriate.
• Differentials: iron deficiency, alpha thalassaemia trait, anaemia of chronic disease, sideroblastic anaemia, lead poisoning, hereditary persistence of fetal haemoglobin.

Reassure and avoid harm

• Explain that beta thalassaemia trait is a harmless inherited trait that does not shorten life and needs no treatment, no routine transfusion, and no regular iron.
• Iron supplements only when iron deficiency is proven (ferritin under 30 micrograms/L): ferrous sulfate 200 mg once daily or on alternate days, stopping when replete; excess iron is harmful.
• Folic acid 400 micrograms daily when planning pregnancy and throughout pregnancy; 5 mg daily if anaemic or if there is a risk of neural tube defects.
• Record the diagnosis to prevent repeated iron courses and further investigations.

Genetic counselling and partner screening

• Offer testing of the partner before pregnancy, or at the first antenatal visit (FBC, haemoglobin analysis, ferritin; DNA analysis if HbA2 is normal but microcytosis persists; alpha thalassaemia and HbS, HbE, HbC screening in at risk populations).
• If both partners are carriers: discuss the 25 percent risk per pregnancy of beta thalassaemia major, and the options of prenatal diagnosis (chorionic villus sampling at 11 to 13 weeks, amniocentesis at 15 to 18 weeks), preimplantation genetic testing, donor gametes, adoption, or acceptance; arrange urgent specialist referral.
• Cascade screening of relatives of carriers; school based and premarital screening in high prevalence regions.

Pregnancy

• Routine antenatal care; check FBC each trimester and ferritin at booking; treat iron deficiency; monitor haemoglobin; transfusion is rarely required; routine obstetric management.

Anaesthesia and surgery

• No special precautions for trait.

Follow up

• No routine haematology follow up; consider repeat FBC every 1 to 2 years; refer to haematology if haemoglobin falls under 90 g/L, splenomegaly or jaundice develops, or the haemoglobin pattern is unusual.