Pernicious anemia is a disease caused by a reduced absorption of vitamin B12 (cyanocobalamin). Vitamin B12 is essential for the correct maturation process of red blood cells (erythrocytes) and is taken through the diet.  Vitamin B12 in fact it is introduced into our body thanks above all to foods such as meat, milk and dairy products.

Pernicious anemia is themegaloblastic anemia that goes with chronic atrophic gastritis, with secretion of reduced or absent intrinsic factor and malabsorption of vitamin B12.

The genesis of gastric atrophy is not fully understood, although it should be noted that patients with pernicious anemia have been found parietal anti-cell antibodies, with percentages of 85-90% in serum, 75% in gastric juice and 60% in plasma cells of the gastric mucosa; these findings have diagnostic significance, although they are not always indicative of the autoimmune pathogenesis of the disease. In fact, even in chronic idiopathic gastritis, without pernicious anemia, the anti-parietal cell antibody is present in 30-60% of cases. A second type of intrinsic factor antibodies has been found in fewer patients with pernicious anemia; the intrinsic antifactor antibodies

Intrinsic factor antibodies are of two types:

  1. L'type I intrinsic factor antibody (blocking antibody) blocks the combinatorial site of intrinsic factor for vitamin B12.
  2. L'type II intrinsic factor antibody (binding antibody) binds to the intrinsic factor + vitamin B12 complex.

Type I antibodies were found in 75% of cases in the serum of patients with pernicious anemia (serum is the liquid part of the blood), type II antibodies were found in about 45% of cases and usually always in presence also of the type I antibody. This type of antibodies have been demonstrated in the gastric juice in the cells of the gastric mucosa: in the blood IgG antibodies predominate, while in the gastric juice those of the IgA type.

The hypothesis, considered very probable, of an autoimmune pathogenesis of pernicious anemia is also supported by the fact that often in people with pernicious anemia coexist other certainly autoimmune diseases (such as Hashimoto's thyroiditis) or presumably autoimmune (such as Addison's disease, hypoparathyroidism, vitiligo).

L'pernicious anemia it is therefore one of the most frequent causes of megaloblastic anemia (or macrocytic anemia). In fact, in this pathology the red blood cells (erythrocytes) are larger than normal. The presence of large red blood cells is linked to vitamin B12 deficiency.

L'pernicious anemia in fact it is characterized by the absence of a particular factor called intrinsic factor which is essential to absorb vitamin B12 in the stomach. In pernicious anemia our stomach is attacked by an autoimmune process, that is an immune process caused by our own organism: the gastric mucosa in particular, its glandular component is damaged and atrophies. There lack of intrinsic factor it is precisely linked to the atrophy of the glandular gastric mucosa, which also produces less hydrochloric acid (the acid part of the so-called "gastric juices"), giving a situation of achlorhydria.

The reduced availability of vitamin B12 makes it difficult the maturation of the red cells (another term to indicate i Red blood cells or erythrocytes). The immature erythrocytes therefore they tend to be larger than normal. Immature red blood cells are called megaloblasts and being defective they are destroyed earlier and to a greater extent than normal: this can be evidenced in blood tests with the finding of high indirect bilirubin (high unconjugated bilirubin).

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Pernicious anemia causes

The causes of pernicious anemia are all those conditions in which there is a megaloblastic anemia secondary to an inflammation of the stomach called chronic atrophic gastritis which lead to a intrinsic factor deficiency and to a consequent malabsorption of vitamin B12.

The main cause of pernicious anemia, is therefore the Biermer's disease, also called aAddison-Biermer nemia, Biermer-Ehrlich anemia, Hunter-Addison anemia, and Lebert essential anemia. It is a dtheeffect of intrinsic factor in the presence of autoimmune chronic atrophic gastritis, or chronic atrophic gastritis type A, a disease characterized by chronic inflammation of the cells of the gastric mucosa linked to the presence of autoantibodies such as intrinsic factor antibodies, anti-proton pump antibodies and anti-gastrin receptor antibodies.

There chronic atrophic gastritis type A represents the 10% of all cases of atrophic gronic gastritis, and is the cause of a progressive loss of the gastric glandular component, with reduced production of intrinsic factor, which is also bound by antibodies to intrinsic factor which alter its intrinsic capacity to bind vitamin B12. All this leads to a lack of absorption of vitamin B12 which can cause the appearance of megaloblastic anemia. In fact, given the particular structure of vitamin B12, its absorption is secondary to the bond with a glycoprotein called intrinsic factor, produced by the parietal cells of the fundus and body of the stomach. In the absence of intrinsic factor, only a small part of cyanocobalamin would be absorbed by simple diffusion.

Pernicious anemia: risk factors

  • Old age
  • Nordic ethnicity
  • Presence of autoimmune diseases (e.g. type I diabetes mellitus, autoimmune thyroiditis, Graves' disease, hypoparatorioidism, Addismus disease, myasthenia gravis, vitiligo)
  • Family history of pernicious anemia

Pernicious anemia: diagnosis

The diagnosis is mainly based on the values of the blood tests: we will have low hemoglobin, hematocrit bass, reduced red blood cell count (low red blood cells), associated with a medium-high corpuscular volume (MCV high) i.e. greater than 90 fl per red blood cell

The state of the gastric muscosa can then be investigated through EGDS (esophagogastroduodenoscopy, more commonly called simply gastroscopy); this examination is in fact able to show the presence of atrophy of the stomach mucosa and allows to take tissue samples (biospies) on which to perform histological analysis.

The search for antibodies to parietal cells (PCA) is positive in 50-80 % of cases), while the search for antibodies to intrinsic factor (IFA) can be positive in more than 50% of cases).

Pernicious anemia: therapy

The therapy of pernicious anemia is based on the administration of high doses of vitamin B12, in quantities higher than those physiologically required in a healthy person, to be taken periodically, in cycles of one month.

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  1. lf 5 years ago

    Good evening,

    at the request of the Gastroenterologist he must carry out the analysis for antibodies to intrinsic factor to look for the causes of the lack of absorption by mouth of vitamin B12, I have already carried out numerous other investigations both blood and instrumental diagnostics and to complete the picture only the factor is missing intrinsic.
    Small problem, I live in Florence and no structure, both private and public, carries out this type of examination, not even in Siena or neighboring ones.
    Could you kindly tell me where I can do it? I am also willing to move to other areas of Italy.
    Thank you so much


    • Testlevels 5 years ago

      I don't know, surely in nearby Lazio there are both public and private structures, otherwise in Veneto

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