Alpha Thalassaemia Trait

Alpha thalassaemia trait is the carrier state for deletion or mutation of one or two of the four alpha globin genes (HBA1 and HBA2 on chromosome 16), causing mild or no anaemia, microcytosis, and normal life expectancy. It must be distinguished from iron deficiency, and its main importance is the risk of severe disease in the offspring of two carriers.

• Silent carrier (-a/aa, one gene deleted): normal haemoglobin and MCV or very slightly reduced MCV; clinically undetectable.
• Alpha thalassaemia trait (two genes deleted): either cis (--/aa, common in Southeast Asian, Mediterranean and Chinese populations) or trans (-a/-a, common in African populations, including East and West Africa); mild microcytic anaemia or normal haemoglobin with low MCV (65 to 75 fL) and low MCH.
• HbH disease (three genes deleted, --/-a): moderate chronic haemolytic anaemia, splenomegaly, and HbH on electrophoresis (not trait).
• Haemoglobin Bart's hydrops fetalis (all four genes deleted): fatal in utero or at birth; occurs when both parents carry the cis deletion (--/aa).
• Frequency: -a/aa deletion in up to 30 to 40 percent of people of African ancestry and the alpha(+) deletion is protective against severe malaria.

• Usually asymptomatic with normal examination.
• Mild trait may show mild pallor, borderline haemoglobin, and no hepatosplenomegaly.
• Trait does not cause jaundice, bone changes, or organ damage; iron overload is not a feature.
• Family history of anaemia or thalassaemia in relatives, or ancestry from an endemic area.
• Red flags that suggest HbH disease and not trait: splenomegaly, jaundice, haemoglobin under 100 g/L, gallstones, and leg ulcers.

• FBC: haemoglobin normal or mildly low (100 to 130 g/L), MCV low (60 to 78 fL), MCH low (under 27 pg), red cell count raised or normal, and normal red cell distribution width, with a Mentzer index (MCV divided by red cell count) under 13.
• Blood film: microcytic hypochromic red cells, target cells, and sometimes HbH inclusions on brilliant cresyl blue staining.
• Iron studies: normal ferritin and transferrin saturation (exclude iron deficiency and treat it first if present).
• Haemoglobin electrophoresis or HPLC: normal HbA2 (2.0 to 3.2 percent) and HbF; this differs from beta thalassaemia trait (raised HbA2). Haemoglobin Bart's (1 to 2 percent) is seen in cord blood of newborns with trait.
• DNA analysis (gap-PCR, multiplex ligation dependent probe amplification, sequencing) is needed to confirm the number of deleted genes, to distinguish cis from trans, and to find non-deletional mutations (Hb Constant Spring).
• Test the partner and perform family studies before pregnancy when both partners are of at risk ancestry.
• Differentials: iron deficiency, beta thalassaemia trait, anaemia of chronic disease, sideroblastic anaemia, lead poisoning.

Reassure and avoid unnecessary treatment

• Explain that the condition is benign, lifelong, does not shorten life, and does not require treatment, regular blood tests, or transfusion.
• Do not give iron unless iron deficiency is proven (ferritin under 30 micrograms/L); excess iron is harmful and does not correct microcytosis.
• Folic acid is not required except in pregnancy (400 micrograms daily, or 5 mg daily if there is anaemia or HbH disease).

Genetic counselling

• Explain inheritance: if one parent has the cis deletion (--/aa) and the other also has an alpha trait, there is a risk of Hb Bart's hydrops fetalis or HbH disease in their children; if both parents have trans (-a/-a) or silent deletions, severe disease is not expected.
• Offer partner testing before conception (FBC, haemoglobin electrophoresis, and DNA analysis if the partner has microcytosis or at risk ancestry).
• Prenatal diagnosis for couples at risk: chorionic villus sampling at 11 to 13 weeks, or amniocentesis at 15 to 18 weeks; fetal ultrasound for cardiomegaly and placental thickness from 12 to 14 weeks; early referral to a fetal medicine unit when both parents carry the cis deletion.
• Preimplantation genetic testing is an option.

Pregnancy

• Routine antenatal care; check haemoglobin and ferritin each trimester; iron if deficient; folic acid 400 micrograms daily periconception and 5 mg daily if anaemic.
• Test the partner early; if the partner carries a deletion, arrange fetal medicine referral before 12 weeks.

Anaesthesia and surgery

• No special precautions for trait.

Follow up

• No routine follow up; record the diagnosis; review if haemoglobin falls, splenomegaly develops, or jaundice appears (reconsider HbH disease); offer counselling to relatives.