Risk Factors For Pernicious Anaemia

Introduction

What is pernicious anaemia?

Pernicious (per-nish-uhs) anaemia (PA) is a rare type of anaemia that occurs due to a deficiency in vitamin B12 resulting from its malabsorption. It is a result of an autoimmune reaction where your body abnormally forms antibodies against the parietal cells of the stomach which produces intrinsic factor (IF) which in turn is responsible for absorbing vitamin B12 from the stomach. It is the most common cause of severe vitamin B12 deficiency in the UK. Additionally, it mostly affects people over 60 years old due to various risk factors. 

What are the symptoms of pernicious anaemia?

Despite improvements in understanding pernicious anaemia, doctors may struggle to make the diagnosis due to its complexity, wide range of clinical presentation, and limitations of currently available diagnostic tools.¹

Its symptoms include:²

• Signs of anaemia such as lightheadedness, headaches, rapid breathing, and feeling tired
• Gastrointestinal symptoms include diarrhoea or constipation, red tongue with or without mouth ulcers, loss of appetite nausea, and weight loss
• Long-term effects on the nervous system include memory problems, problems with vision, irritability, difficulty concentrating, hallucinations, depressive mood, and delusions

What is the mechanism of pernicious anaemia?

The main problem with pernicious anameia is that the parietal cells of the stomach are unable to make the intrinsic factor (IF) which is important for vitamin B12 absorption from the stomach.³ Normally, the IF transports vitamin B12 from food to specific cells in the small intestine. From there, vitamin B12 enters your circulation. Other proteins then transport vitamin B12 to the bone marrow, where it is needed to produce new red blood cells. When your immune system prevents your intrinsic factor from functioning properly, this process cannot occur.⁴

Are there risk factors for pernicious anaemia?

Identifying risk factors for any disease is important to avoid or decrease its occurrence in the future, if possible. However, since PA occurs as a result of an autoimmune process in the body, it cannot be prevented. Alternatively, its symptoms can be reduced by restoring the level of vitamin B12 in the body. 

It is important to differentiate between PA and other causes of vitamin B12 deficiency because PA is one of the main causes of megaloblastic anaemia. Various causes of vitamin B12 insufficiency, such as gastrointestinal disorders and gastrointestinal surgery, may only be managed to the degree that they are avoidable. Vegetarians can avoid vitamin B12 shortage by taking B12 supplements. An oral dosage of 100-200 mcg administered weekly should be sufficient. 

Risk factors for vitamin B12 deficiency anaemia 

Genetic risk factors

It is known that PA has a strong autoimmune origin while other causes of vitamin B12 deficiency do not. However, the genetic susceptibility factors have not been adequately researched. The mechanism of action is through autoantibodies which then attack the parietal cells of the stomach, resulting in a decrease in the synthesis of intrinsic factors. Some cases of PA are associated with other autoimmune diseases such as autoimmune thyroid disease, Addison’s disease, vitiligo or diabetes mellitus type 1, which indicates a common genetic background.⁵

The familial risk for such a disease is important, indicating a complex genetic aetiology. The findings of one research study suggest that more population-level research is needed to clarify the processes of familial pernicious anaemia, which could be helpful in understanding the disease's aetiology.⁶ 

Two essential facts support the presence of a genetic foundation. First, PA has a familial relationship, with around 19% of patients having a family member with PA. On the other hand, it was discovered that the genes HLA-DRB1*03 and DRB1*04 were strongly related to PA. These types of genes have been found in other autoimmune disorders, supporting the idea that autoimmunity may play a role in PA.⁷

Dietary factors

If you are on a restricted diet that does not include animal products such as fish, meat, poultry, eggs, and dairy products, which are the main source of vitamin B12, or you are poorly eating in general, then you are at risk of developing vitamin B12 deficiency. 

Your daily needs for vitamin B12 is determined by your age. The recommended daily amount for adults is 2.4 mcg.⁸ Vitamin B12 is one of the primary 'raw materials' required to construct healthy red blood cells— the other is folate or folic acid. If you are deficient in either B12 or Folate, or both, your body will be unable to create healthy red blood cells, which will prevent oxygen from being efficiently delivered throughout your body.

Age, gender and ethnicity

Epidemiological studies show that PA affects 0.1% of the general population and 2-3% of those over 65 years old. AFAB are at double the risk than AMAB. PA may impact persons of any age, although the risk often rises with age.⁹ Similarly, although PA primarily affects older women of Northern European heritage, new studies have demonstrated a similar frequency of PA in other ethnicities (e.g., Caucasian, African, and American), with an earlier beginning of the pathological disease.¹⁰ 

Medical conditions

If you have the following medical conditions then you might be at risk of developing vitamin B12 deficiency anaemia:¹¹

• You had a bariatric surgery i.e. having part of your stomach removed as part of a surgery to decrease the stomach size and help in weight loss. The section removed results in loss of production of the intrinsic factor thus decreased vitamin B12 absorption
• You have other autoimmune disorders such as autoimmune thyroid disease, Addison’s disease, vitiligo or diabetes mellitus type 1, as researchers concluded a link between these diseases and pernicious anaemia
• You take medications that inhibit your body from adequately absorbing vitamin B12. Examples include: proton pump inhibitors that are used in gastritis and reflux disease, metformin, and nitrous oxide
• You suffer from other medical conditions that hinder absorption from the small intestine such as coeliac disease or Crohn’s disease
• You have a condition called functional vitamin B12 deficiency where the transporter that carries the vitamin is low while the vitamin level itself is normal

Lifestyle factors

Smokers are in general at risk for many vitamin deficiencies, including vitamin B12. The findings of one study revealed that while blood levels of total vitamin B12 may not differ between smokers and nonsmokers, the function of this vitamin is impaired in the bodies of smokers due to a drop in serum levels of the active form of vitamin B12.¹²

Alcohol consumption, specifically chronic alcohol abuse, can lead to both vitamin B12 and folate deficiency. Chronic alcohol abuse has a direct harmful effect on the liver cells, as well as through another mechanism which increases homocysteine, an amino acid which if accumulated would result in an increased risk of heart diseases, in addition to increased risk of cancers and dementia.

Summary

Pernicious anaemia is a rare type of vitamin B12 deficiency, primarily affecting those over 60, resulting from vitamin B deficiency due to impaired absorption. This condition stems from an autoimmune reaction where the body produces antibodies against stomach parietal cells responsible for intrinsic factor production, which is vital for B12 absorption. Symptoms vary widely, including signs of anaemia, gastrointestinal issues, and long-term neurological effects. While pernicious anaemia cannot be prevented due to its autoimmune nature, symptoms can be managed through B12 supplementation.

Risk Factors include:

• Genetic predisposition plays a role only in pernicious anaemia but not other types of vitamin B12 deficiency
• Dietary factors, particularly restrictive diets or poor eating habits, increase susceptibility. 
• Medical conditions like bariatric surgery, autoimmune disorders, and certain medications hinder vitamin B12 absorption
• Lifestyle factors such as smoking and alcohol misuse also contribute to vitamin B12 deficiency

Understanding these risk factors is crucial for effective management and prevention of complications.