What is Pernicious Anaemia ?

To fully grasp the nature and cause of Pernicious Anaemia we will have to understand some basic biochemistry. And we will do this by keeping things as simple as possible. For over a hundred years doctors and scientists struggled to understand why some of their patients were dying of a disease that was first identified in the middle of the nineteenth century, and the secrets of the disease revealed themselves only after being the centre of attention by some very clever people. Indeed, no fewer than six Nobel Prizes were awarded to doctors and scientists who made breakthroughs that helped understand the disease. We shall begin by looking at the nature of Pernicious Anaemia itself.

Pernicious Anaemia is an autoimmune disease

Autoimmune Diseases occur when the body produces something that harms itself. There are many types of autoimmune diseases including Type 1 Diabetes, Alopecia, Multiple Sclerosis, Vitiligo, Psoriatic Arthritis and Graves’ Disease. Patients who have one autoimmune disease tend to develop other autoimmune diseases. The most common co-existing autoimmune disease for patients with Pernicious Anaemia is Hashimoto’s Thyroiditis.1

Introducing Intrinsic Factor

A normal healthy person will produce a protein in their stomach called Intrinsic Factor. Intrinsic Factor is produced by Parietal Cells.

Parietal Cells

Parietal Cells are found in the lining of the stomach. As well as producing Intrinsic Factor, Parietal Cells also produce Hydrochloric Acid. Intrinsic Factor is essential for B12 Absorption whilst Hydrochloric Acid allows B12 to be released from food.
Parietal Cells may fail due to infection (from Helicobacter pylori for example) or because the body produces antibodies that kill off the Parietal Cells – Parietal Cell Antibodies. If a patient produces Parietal Cell Antibodies these would attack the Parietal Cells which would mean that he or she wouldn’t be able to produce Intrinsic Factor. However, the existence of Parietal Cell Antibodies cannot be used to diagnose Pernicious Anaemia. This is because although around 80% of patients who have Pernicious Anaemia will have the Parietal Cell Antibodies, around 10% of the general population will also have the antibodies.2 It used to be the case that doctors would diagnose a patient with Pernicious Anaemia simply because of the existence of the Parietal Cell Antibodies, which seems to make sense because he or she wouldn’t be able to produce the Intrinsic Factor due to their Parietal Cells not working, but this is not the case now.

Intrinsic Factor then, is produced by Parietal Cells that line the wall of the stomach. Intrinsic Factor is responsible for extracting vitamin B12 from food. The only food that contains vitamin B12 comes from animals and includes milk, cheese, fish, eggs, shellfish, meat (especially offal) and insects. There is no B12 in vegetables or fruit and this is why Vegans and Vegetarians are vulnerable to becoming deficient in B12 and why so many take B12 supplements in the form of tablets or skin patches to reduce the risk of becoming B12 deficient.

Intrinsic Factor Antibodies

People with Pernicious Anaemia produce Intrinsic Factor Antibodies. These antibodies attack any Intrinsic Factor that has been produced by the Parietal Cells and render them useless. And because the patient now has no functioning Intrinsic Factor he or she cannot absorb vitamin B12 from any animal product that has been swallowed. As a consequence of not having any functioning Intrinsic Factor the patient becomes deficient in B12. Vitamin B12 is one of the three necessary ingredients that produces healthy, functioning red blood cells.

Red Blood Cells (RBCs, Erythrocytes)

Red Blood Cells are produced in bone marrow. Red blood cells main function is to transport oxygen throughout the body via arteries. Oxygen is needed everywhere in the body and so if a person has unhealthy disfunctioning red blood cells he or she will feel very unwell and will eventually die. The red blood cell transports the oxygen by way of the major component of red blood cells – Haemoglobin. Without adequate supplies of B12 a person will be unable to make healthy red blood cells. Healthy red blood cells are circular and have a concave centre.

Without B12 the cells become a strange shape and in around 65% of cases will become enlarged. Enlarged red blood cells are called Megaloblasts and the patient will be diagnosed as having Macrocytosis. Whether the Red Blood Cell is enlarged or not, because it is a strange shape it will not be able to carry the molecule that transports the oxygen – haemoglobin. Unfortunately, some doctors will only investigate the patients B12 status if he or she has Macrocytosis. Many, but not all patients with low B12 will have enlarged red blood cells.


Haemoglobin is made up of two elements. Haem which is iron, and a protein called Globin. It stands to reason therefore that if a person is deficient in iron then he or she will be unable to make Haemoglobin. And if a person becomes deficient in Haemoglobin due to Iron Deficiency he or she is diagnosed as having Iron Deficiency Anaemia. Iron Deficiency is a major problem especially in some geographic areas of the world and in individual countries.
If a person has adequate supplies of iron then it bonds to the globin in the red blood cell, and oxygen, that you will have inhaled through your lungs, attaches itself to the iron part of the haemoglobin. The oxygen is then transported to wherever it is needed. Here’s how one author puts it:

Think of the red blood cell as a bus. The bus is made of raw materials…(B12) and once made it takes on board haemoglobin and sets off for the lungs. Waiting in the lungs is a queue of oxygen molecules which hop on the bus (into the blood cell) where they immediately bond to the iron in the haemoglobin. The bus carries on to wherever the oxygen is needed and when it arrives, the doors open, the oxygen molecules release their grip on the haemoglobin and exit the bus. The red blood cells then return to the lungs, taking with them some waste products as they do so3

So, without adequate supplies of Vitamin B12 a person will not be able to build healthy red blood cells. Unhealthy red blood cells means the patient will have low haemoglobin. And a lack of haemoglobin is what is meant by Anaemia. (which literally means ‘lack of blood’ though it should refer to ‘lack of healthy blood’ as the patient will have normal amounts of blood but it will be lacking haemoglobin).


Anaemia is derived from two Greek words “an”, meaning lack of, and “haema” – blood. So anaemia literally means lack of blood. There are over 90 different types of anaemia including blood loss through trauma. But we are interested in one cause of low haemoglobin, lack of B12. As we have seen, if a person has low or very low levels of B12 then he or she won’t be able to make the healthy red blood cells. And because the red blood cells are a strange shape they won’t be able to carry haemoglobin. He or she will be lacking oxygen in their body and consequently will feel continually tired and exhausted, won’t be able to think clearly and will suffer from many other symptoms. If the B12 Deficiency is not addressed, then he or she will die. And that’s where the ‘pernicious’ part of Pernicious Anaemia comes from. Before it was able to be treated, people who became anaemic due to lack of B12 died.

The Importance of Vitamin B12

Vitamin B12 is one of the main ‘raw materials’ needed to build the healthy red blood cell; the other is folate or folic acid.* If a patient is deficient in either B12 or Folate or both then he or she will be unable to produce healthy red blood cells (the bus) and so the oxygen won’t be able to be carried around the body.

Folate is the naturally occurring form of vitamin B9 found in leafy green vegetables whereas Folic Acid is a fully oxidized synthetic compound (pteroylmonoglutamic acid used in food fortification and dietary supplements).

Summary So Far

In order to make healthy red blood cells that can carry oxygen around the body you need adequate levels of B12 and Folate. To ensure healthy Haemoglobin is made that can carry the oxygen you will need adequate supplies of Iron. If a patient is deficient in B12 or Folate or Iron or all three, then he or she will not be able to transport that oxygen. Vitamin B12 is absorbed from food with the help of Intrinsic Factor. A patient who produces antibodies that ‘kill off’ the Intrinsic Factor is diagnosed as having Pernicious Anaemia.

Pernicious Anaemia

People who have been diagnosed as having Pernicious Anaemia will be unable to absorb Vitamin B12 from food.4 Until the 1920’s when it was discovered that feeding patients raw, or very lightly cooked liver could keep them alive patients died from the disease. Injectable ‘artificial’ B12 became available after the Second World War and now, as long as the diagnosis is made, people seldom die of the disease. Once the Vitamin B12 Deficiency is corrected patients can live a more or less normal life. However, a great many people still have problems with symptoms after the deficiency has been corrected though doctors don’t know why this is so. When a patient has been treated with replacement therapy B12 then he or she should have their anaemia corrected and therefore will not have any anaemia that will prove ‘pernicious’ (fatal). So therefore they will not have Pernicious Anaemia any more. But the fact is that they will need replacement therapy B12, preferably in a form that by-passes their stomach, for life. They will always need B12 and their treatment should never be stopped. Here’s what the latest Guidelines from the British Committee for Standards in Haematology state:

(testing positive for Intrinsic Factor Antibodies)…
identifies those with a need for lifelong cobalamin replacement therapy.5

Cobalamin is the scientific name for B12. Whilst B12 will correct a patient’s anaemia and therefore save his or her life, the patient will still have Autoimmune Metaplastic Atrophic Gastritis (AMAG) and so perhaps it is time to replace the diagnosis of Pernicious Anaemia with this more accurate description of their condition. Note whilst AMAG (or Pernicious Anaemia) can be treated, there is no cure for the condition yet.


Nobody really knows how many people in the world are deficient in B12. This is because there is no genuine consensus on what constitutes a deficiency. In the UK, different laboratories have different thresholds which means that in one part of the country your results could be interpreted as being deficient whilst in another part of the country you would be told your levels are fine. And then there’s the problem with defining what is a sub-clinical deficiency where the results are above any threshold but the patient could still be deficient.

Most commentators believe that in the modern world around 10% of the population is deficient in this essential vitamin, however, it is impossible to say how many peoples’ deficiency will be caused by Pernicious Anaemia. And the reason it’s not possible to give an active figure is because the test for Pernicious Anaemia, the Intrinsic Factor Antibody Test, is only around 50% accurate. This means that may patients are told that their B12 deficiency is not caused by Pernicious Anaemia because they tested negative for the Intrinsic Factor Antibody whereas, in reality, the cause will be Pernicious Anaemia. We estimate that between 50% and 70% of people with low B12 will have Pernicious Anaemia as the cause of that deficiency, but they are not diagnosed because of the limitation of the test for the Intrinsic Factor Antibody. Until a new, more accurate test is developed (or the Schilling Test is re-introduced) there will be a sizeable number of people who will perhaps have been diagnosed as being deficient in B12 but, because the Intrinsic Factor Antibody test proved negative, will have been given no explanation as to the cause of their deficiency.

For a full explanation of the difference between B12 Deficiency and Pernicious Anaemia please click here.


  1. Hooper M. What You Need to Know About Pernicious Anaemia and Vitamin B12 Deficiency; Hammersmith Health Books, London; 2014.pp 115-120
  2. Devalia V, Hamilton MS, Molloy A-M. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. British Journal of Haematology; 2014; 166(4): 496-513
  3. See Hooper (above)
  4. Stabler S, Allen R. Vitamin B12 Deficiency as a worldwide problem. Annual Review of Nutrition 2004; 24:299-326
  5. See Devalia et al above
  6. Andres E, Serraj K. Optimal management of pernicious anemia. Journal of Blood Medicine 2012; 3:97-103

Pin It on Pinterest

Share This