[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Red cells and bleeding disorders](https://durgical.com/en/general-pathology/areas/red-cells/) › Thalassaemias: β and α

# Thalassaemias: β and α

- Lesion

Too few globin chains of one kind: cells are small and pale, the unpaired chains clump and kill precursors, and iron builds up.

Updated Nov 12, 2026

## Key points

- β-thalassaemia major: severe transfusion-dependent anaemia from about six to nine months; HbF high, HbA absent or low.
- β-thalassaemia minor (trait): mild microcytosis, target cells, raised HbA2; can be mistaken for iron deficiency.
- Iron overload from transfusions and erythroferrone-mediated hepcidin suppression; cardiac haemosiderosis is a leading cause of death.
- α-thalassaemia: four genes; one deleted is silent, two is trait, three is HbH disease (β4 tetramers), four is Hb Bart (γ4) hydrops fetalis.
- Crew-cut skull, maxillary overgrowth and massive hepatosplenomegaly in untreated major disease.

On this page

- The basics Key points
- What it is
- Structure
- Step by step
- Thalassaemia syndromes
- Markers
- Memory aid
- Elsewhere in DurgiPedia

- Clinical Clinical notes

- Study Test yourself

- Connections Connections

## What it is

The thalassaemias are inherited disorders in which synthesis of α- or β-globin chains is reduced or absent. Beta-thalassaemia is usually caused by point mutations (splicing, promoter, chain-terminating) and alpha-thalassaemia by gene deletions. The missing chain causes underhaemoglobinized microcytic cells; the surplus chain is the real culprit. In β-thalassaemia free α chains precipitate and kill erythroid precursors in the marrow (ineffective erythropoiesis), which drives marrow expansion, extramedullary haematopoiesis and excessive iron absorption through suppression of hepcidin.

## Structure

- Smear: microcytosis, hypochromia, marked anisopoikilocytosis, target cells, basophilic stippling, nucleated red cells.
- Marrow: striking erythroid hyperplasia with dying precursors.
- Bone: expanded marrow erodes cortex; new bone forms perpendicular spicules (crew-cut on radiograph).
- Organs: haemosiderosis and secondary haemochromatosis in liver, heart and endocrine glands; spleen enlarged by extramedullary haematopoiesis.

## Step by step

- Mutations reduce β-globin (β+) or abolish it (β0); deletions remove α-globin genes.
- Less HbA forms: small, pale cells.
- Unpaired α chains precipitate in precursors, damaging membranes: most die in the marrow.
- Severe anaemia raises erythropoietin; the marrow expands and haematopoiesis spreads to spleen and liver.
- Erythroid precursors release erythroferrone, which suppresses hepcidin: gut iron absorption rises.
- Iron from absorption and transfusions deposits in heart, liver and glands.

## Thalassaemia syndromes

| Syndrome | Genotype | Clinical picture | Haemoglobin findings |
| --- | --- | --- | --- |
| [β-thalassaemia major](https://durgical.com/en/conditions/thalassemias/) | Two defective β alleles (β0 or β+) | Severe anaemia from infancy, transfusion-dependent | Mostly HbF; little or no HbA |
| [β-thalassaemia minor (trait)](https://durgical.com/en/conditions/thalassemias/) | One defective β allele | Mild microcytic anaemia, often none | HbA2 raised |
| [Silent carrier](https://durgical.com/en/conditions/thalassemias/) | One α gene deleted | None | Normal or slight microcytosis |
| [α-thalassaemia trait](https://durgical.com/en/conditions/thalassemias/) | Two α genes deleted (same or opposite chromosomes) | Mild microcytic anaemia | Normal HbA2; Hb Bart at birth |
| [HbH disease](https://durgical.com/en/conditions/thalassemias/) | Three α genes deleted | Moderate haemolytic anaemia | HbH (β4) inclusions |
| [Hb Bart hydrops fetalis](https://durgical.com/en/conditions/thalassemias/) | Four α genes deleted | Fetal death or severe hydrops | Hb Bart (γ4) with very high oxygen affinity |

## Markers

- HbA2
- HbF
- HbH inclusions
- Ferritin

## Clinical notes

- Trait vs iron deficiency: thalassaemia trait has a normal or high red cell count, normal ferritin and raised HbA2 (in β-trait).
- Chelation prevents cardiac death; stem cell transplantation and gene therapy can cure β-thalassaemia major.

## Memory aid

In thalassaemia it is not the missing chain that kills, it is the lonely partner that precipitates.

## Test yourself

Think of the answer, then tap the question to see it.

## Why is erythropoiesis ineffective in β-thalassaemia major?

Excess unpaired α chains precipitate in erythroid precursors, damaging membranes so most die in the marrow.

## Which haemoglobin is raised in β-thalassaemia trait?

HbA2 (α2δ2).

## Why do patients absorb too much iron?

Expanded erythroid precursors release erythroferrone, which suppresses hepcidin and increases gut iron uptake.

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## Elsewhere in DurgiPedia

- [Hemoglobin variants (HbA, HbA2, HbF, HbS, HbC)](https://durgical.com/en/biochemistry/topics/hemoglobin-variants/)
- [Hemoglobin and 2,3-BPG](https://durgical.com/en/biochemistry/enzymes/hemoglobin-and-2-3-bpg/)

## Connections

## Related 4

- [Fetal hydrops: immune and nonimmune](https://durgical.com/en/general-pathology/fetal-hydrops-immune-and-nonimmune/)
- [Hemochromatosis: hepcidin, HFE and where iron settles](https://durgical.com/en/general-pathology/hemochromatosis-hepcidin-hfe-and-where-iron-settles/)
- [Iron deficiency anaemia](https://durgical.com/en/general-pathology/iron-deficiency-anaemia/)
- [Sickle cell disease](https://durgical.com/en/general-pathology/sickle-cell-disease/)

## Related conditions 3

- [Thalassemias (α and β)](https://durgical.com/en/conditions/thalassemias/)
- [Hereditary hemochromatosis](https://durgical.com/en/conditions/hereditary-hemochromatosis/)
- [Iron deficiency anaemia](https://durgical.com/en/conditions/iron-deficiency-anaemia/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Beta thalassemia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/beta-thalassemia/) (MedlinePlus, US National Library of Medicine, 2026); [Alpha thalassemia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/alpha-thalassemia/) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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