Synopsis
Differentiate alpha- from beta-globin underproduction, distinguish carrier states from iron deficiency, recognise clinically significant genotypes, and coordinate molecular diagnosis, reproductive counselling and complication surveillance.
- Thalassaemias are inherited reductions in alpha- or beta-globin synthesis, causing microcytosis, globin-chain imbalance and ineffective erythropoiesis of variable severity.
- Trait commonly produces a low MCV and MCH out of proportion to mild or absent anaemia, with a relatively preserved red-cell count.
- Check ferritin before attributing microcytosis to carrier status; iron deficiency and thalassaemia can coexist and only documented deficiency should receive iron.
- Beta-thalassaemia trait usually raises haemoglobin A2 after infancy, while iron deficiency, recent transfusion and some variants can complicate quantification.
- Alpha-thalassaemia trait often has normal adult high-performance liquid chromatography or electrophoresis, so molecular testing may be required when reproductive risk matters.
- Loss of one alpha gene is usually silent, two causes trait, three produces HbH disease, and loss of all four causes alpha-thalassaemia major with fetal hydrops.
- Beta-thalassaemia phenotypes range from asymptomatic carrier to non-transfusion-dependent and transfusion-dependent disease according to the paired variants and modifiers.
- HbH disease can produce chronic haemolysis, splenomegaly, gallstones and oxidative crises with infection or medicines, especially in non-deletional forms.
- Carrier identification is clinically important for reproductive counselling, but should not be presented as illness, racialised assumption or a reason to deny normal activity.
- At-risk couples require counselling that integrates both partners' results, cis or trans alpha-gene arrangement, variant severity and available prenatal or preimplantation options.
Key red flags
Both partners carrying alpha-zero deletions in cis creates a pregnancy at risk of alpha-thalassaemia major requiring urgent fetal referral.
Investigation priorities
Define microcytosis, red-cell number and haemolytic morphology.
Management branches
A low MCV or MCH persists with mild or no anaemia.
- Obtain ferritin with inflammatory context and review diet, bleeding, pregnancy, transfusion, ancestry and family blood-count history.
- Perform accredited haemoglobin analysis before iron treatment when deficiency is not established, recognising the limitations for alpha trait.
- Refer for molecular testing when results are discordant, HbH is possible or a partner combination could create a severe fetal genotype.
Key medicines
Folic acid in significant haemolysisSpecialists commonly prescribe 5 mg orally once daily during pregnancy or sustained HbH or intermedia haemolysis when erythropoietic demand makes folate depletion plausible.Assess vitamin B12 where appropriate and do not let folate obscure the need to investigate a new anaemia or provide genotype-specific care.
Iron replacement for proven deficiencyUse the NICE or BNF oral elemental-iron regimen and duration only after deficiency is demonstrated, adjusting frequency for tolerance and expected absorption.Avoid indefinite empirical iron because intermedia syndromes may already absorb excess iron; confirm response and investigate the source of deficiency.