Pernicious anaemia - Macrocytic anaemia

Pernicious anaemia

Definition

In pernicious anaemia, atrophy of the gastric mucosa causes failure of intrinsic factor production, vitamin B12 deficiency and megaloblastic anaemia.

Incidence

1 in 8000 over 60 years.

Age

More common in the elderly.

Sex

F > M

Aetiology/pathophysiology

The gastric parietal cells normally produce intrinsic factor (IF) that binds to vitamin B12 allowing it to be absorbed in the terminal ileum.

·        90% of patients with pernicious anaemia have autoan-tibodies to the gastric parietal cells; however, autoantibodies may occur in association with gastric atrophy without pernicious anaemia.

·        50% of patients have antibodies to intrinsic factor, which are specific for this diagnosis and may be blocking antibodies (bind to intrinsic factor and prevents binding to B12) or binding antibodies (bind to the IF:B12 complex preventing absorption).

Atrophic gastritis is present with plasma cell and lymphoid infiltration affecting the fundus and body of the stomach. There is achlorydia and absent secretion of intrinsic factor.

Clinical features

The onset of pernicious anaemia is usually insidious with worsening symptoms of anaemia. Patients may also have neurological complications of vitamin B12 deficiency.

Investigations

Full blood count will demonstrate a macrocytic anaemia (raised MCV). Vitamin B12 is low. The Schilling test is used to differentiate the causes of vitamin B12 deficiency (see Table 12.4).

Management

Parenteral vitamin B12 replacement is required for life. Clinical improvement can be seen in 48 hours and a reticulocytosis can be demonstrated 2–3 days after commencing therapy.