Pernicious anaemia: symptoms, causes, tests and B12 treatment

The NHS says symptoms of vitamin B12 deficiency anaemia can be wide-ranging. They usually develop gradually but can worsen if the condition goes untreated. Some of them can also happen when someone has a B12 deficiency but has not yet developed anaemia, which is why symptoms matter as well as blood counts.

Because vitamin B12 helps keep the nervous system healthy, a deficiency can also cause symptoms that affect the brain and nerves.

Vitamin B12 from food is combined with a protein called intrinsic factor in the stomach. This mix is then absorbed in a part of the gut called the distal ileum. In pernicious anaemia, the NHS explains, the immune system attacks the cells in the stomach that produce intrinsic factor, so the body is unable to absorb vitamin B12.

This is a problem of absorption, not of how much B12 you eat. The NHS says most people with B12 deficiency anaemia have underdeveloped red blood cells that are larger than normal, which is called megaloblastic anaemia.

The Pernicious Anaemia Society, a UK patient charity, describes the same mechanism: either intrinsic factor is not produced, or it is produced but destroyed by antibodies. In both cases B12 cannot be absorbed from food.

The NHS says vitamin B12 deficiency anaemia is usually treated with injections of hydroxocobalamin, given by a GP or nurse. At first the injections are given every other day. Because pernicious anaemia is not related to diet, the NHS says you will usually then need an injection every 2 to 3 months for the rest of your life.

If you have neurological symptoms such as numbness or tingling in the hands and feet, the NHS says you will be referred to a haematologist and may need injections every 2 months. NICE CKS describes the same pattern: hydroxocobalamin 1 mg three times a week for 2 weeks, then every 2 to 3 months for life where the deficiency is not diet-related. It also says daily large oral doses (500 to 1000 micrograms) may be considered as an alternative.

The NHS says that for injections given in the UK hydroxocobalamin is preferred to cyanocobalamin because it stays in the body for longer.

To check treatment is working, a blood test is often done around 7 to 10 days after starting, and another after about 8 weeks. The NHS says most people do not need further monitoring unless symptoms return or treatment is ineffective.

The NHS says B12 deficiency anaemia can often be diagnosed by a GP based on symptoms and blood tests. The tests check whether haemoglobin is lower than normal, whether the red blood cells are larger than normal, and the levels of vitamin B12 and folate.

The NHS also notes that symptoms must be taken into account. Some people have symptoms and seem to have normal vitamin levels, and some have low levels despite having no symptoms. To look for the cause, extra blood tests may check for pernicious anaemia. The NHS says these tests are not always conclusive, but can often give a good idea.

NICE CKS says diagnosis should be made through history, examination and investigations including a full blood count, blood film and measurement of folate and B12. It says an anti-intrinsic factor antibody test should be considered if autoimmune gastritis is suspected or there are strong clinical features of B12 deficiency. The Pernicious Anaemia Society says a positive antibody test makes pernicious anaemia very likely but a negative result does not rule it out.

You may be referred to a haematologist if the cause is uncertain, if you are pregnant or if symptoms suggest your nervous system is affected. A gastroenterologist may be involved if the gut is not absorbing B12 properly.

The NHS says the exact cause of pernicious anaemia is unknown, but it is more common in women around 60 years of age, people with a family history of the condition and people with another autoimmune condition, such as Addison's disease or vitiligo.

Other causes of B12 deficiency are described separately by the NHS and NICE CKS. They include a diet with no meat, fish or dairy that is not supplemented (such as a vegan diet without B12 supplements), stomach operations such as a gastrectomy, intestinal conditions such as Crohn's disease, and some medicines including proton pump inhibitors, metformin and nitrous oxide. The NHS says B12 stores in the body can last around 2 to 5 years without being replenished, so problems from diet can take a long time to develop.

The NHS also says that both B12 and folate deficiency are more common in older people, affecting around 1 in 10 people aged 75 or over and 1 in 20 aged 65 to 74.

The NHS says complications are rare because most cases are easily treated, but they can develop if you have been deficient for some time. They include neurological problems such as vision problems, memory loss, pins and needles, loss of coordination and damage to the nerves, particularly in the legs. If neurological problems develop, the NHS says they can sometimes be irreversible.

B12 deficiency can sometimes lead to temporary infertility, which usually improves with treatment. Adults with severe anaemia are at risk of heart problems such as heart failure. In pregnancy, the NHS says not having enough B12 can increase the risk of a neural tube defect in the baby, so anyone who is pregnant and has B12 deficiency should discuss it with their doctor or midwife.

The NHS also says that if your B12 deficiency is caused by pernicious anaemia, your risk of developing stomach cancer is increased.

Folic acid alone should not be used to treat a possible B12 deficiency. The NHS says folic acid treatment can sometimes improve symptoms so much that it masks an underlying B12 deficiency, which could then affect the nervous system, so B12 levels are checked first.

See a GP if you think you may have a vitamin B12 or folate deficiency. The NHS says it is important for B12 deficiency anaemia to be diagnosed and treated as soon as possible, because although many symptoms improve with treatment, some problems can be irreversible.

Numbness, pins and needles, balance problems, vision changes or memory change together with unexplained tiredness are reasons to ask for a B12 check. If you already have a B12 deficiency and develop new neurological symptoms, tell your GP promptly, as NICE CKS advises urgent specialist advice for neurological involvement.

Treatment is lifelong, so regular injections become part of routine care. The Pernicious Anaemia Society provides information and support groups, and campaigns for better diagnosis and treatment. If symptoms continue between injections, raise this with your GP rather than assuming it is unrelated.

Diet alone does not fix pernicious anaemia, because the problem is absorption. The NHS lists meat, salmon and cod, milk and other dairy products and eggs as sources of B12, with some fortified foods such as certain yeast extracts and breakfast cereals for vegetarians and vegans, which matter mainly when the deficiency is diet-related.

On the NHS the GP is usually the first step. They can arrange blood tests, start treatment and refer to a haematologist or gastroenterologist if needed. Injections are typically given by a GP or practice nurse, with the schedule set by your clinician.

Some people choose to see a haematologist or gastroenterologist privately for tests or a second opinion. In either setting it is worth asking which antibody and B12 tests are included, how often injections will be given long term, and who will monitor you, so that your GP has a complete record.