Thalassemia

For medical students2 min readUpdated 2026-10-10

Thalassemia is a group of inherited blood disorders caused by impaired quantitative synthesis of globin chains. The deficiency of these chains leads to their excessive accumulation, destruction of red blood cells, and the development of severe anemia.

Core pathologyImbalance of globin chains leading to ineffective erythropoiesis.

Genetic basisMutations in genes responsible for the synthesis of alpha- or beta-globin chains.

Key featureAccumulation of unbalanced globin chains in the cytosol of erythroid cells.

Main formsAlpha-thalassemia (chromosome 16) and beta-thalassemia (chromosome 11).

Pathophysiology

The pathogenesis is based on a primary deficiency of one of the globin chains. Excessive, "unpaired" globin chains cannot incorporate into hemoglobin and precipitate within the cytosol of erythroid cells, forming aggregates (Heinz bodies). This leads to two critical consequences:

Ineffective erythropoiesis: destruction of erythrokaryocytes directly within the bone marrow.
Extravascular hemolysis: premature destruction of circulating reticulocytes and erythrocytes in the spleen.

The final result is pronounced erythropenia and anemia.

Classification

The disease is divided depending on the affected chain:

Alpha-thalassemia: determined by 4 genes on chromosome 16. Severity ranges from silent carrier state (1 gene) to lethal hydrops fetalis (4 genes).
Beta-thalassemia: determined by 2 genes on chromosome 11. There are three forms:
Thalassemia minor: mutation of 1 gene, mild clinical course.
Thalassemia intermedia: partial impairment of expression of 2 genes.
Thalassemia major (Cooley's anemia): complete cessation of expression of 2 genes, requires regular blood transfusions.

Principles of Management

Treatment is structured at three levels:

Etiotropic: targeting factors that disrupt the proliferation and differentiation of blood cells.
Pathogenetic: aimed at interrupting the mechanisms of anemia, combating hypoxia and hemosiderosis, and correcting acid-base disorders.
Symptomatic: relief of the consequences of anemia (headaches, sleep disturbances).

Mnemonic

Alpha = 4 genes (like 4 corners of the earth), Beta = 2 genes (like 2 sides of a coin).

Frequently asked questions

What etiotropic therapies for thalassemia are used in practice?

Etiotropic treatment aims to eliminate or stop the cause of the disease.

From the methods directly indicated in sources:

in beta-thalassemia major, allogeneic bone marrow transplantation is the definitive treatment; it is cited as the only curative method;
for diseases caused by genomic alterations, gene therapy is indicated as a method for correcting genetic defects, though it remains in the stages of development, trials, and partial application.

Why does anemia develop in thalassemia?

Anemia occurs due to the destruction of erythroid cells in the bone marrow (ineffective erythropoiesis) and accelerated destruction of defective erythrocytes in the spleen.

What is the difference between thalassemia minor and thalassemia major?

The minor form is caused by a mutation in a single gene and is nearly asymptomatic. The major form (Cooley's anemia) is caused by the complete inactivation of two genes and requires regular blood transfusions.

What are Heinz bodies?

These are aggregates of excess globin chains that precipitate in the erythrocyte cytosol, damaging the cells and provoking hemolysis.

Go deeper

Differential diagnosis of microcytic anemias.
Mechanisms of hemosiderosis development with frequent blood transfusions.
Features of laboratory diagnostics (sideroblasts, anisocytosis, hypochromia).
Genetic aspects of chromosome 16 and 11 mutation inheritance.