What Is Pernicious Anaemia 

  • Shazia Asim PhD Scholar (Pharmacology), University of Health Sciences Lahore, Pakistan
  • Yuna Chow BSc (Hons), Medicine, University of St Andrews

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Pernicious anaemia is a rare autoimmune disease, characterized by a deficiency of vitamin B12, which is essential for the production of red blood cells. This autoimmune reaction is typically directed against the parietal cells in the stomach, which produce intrinsic factor, a substance necessary for B12 absorption.1

Pernicious anaemia: a multifaceted haematological enigma

Pernicious Anaemia is a complex, multifactorial autoimmune disease. It is a neglected disorder in many medical settings and is underdiagnosed in many patients. This disease is linked to autoimmune gastritis, which is a different condition. Pernicious anaemia occurs in a later stage of autoimmune gastritis where gastric intrinsic factor deficiency and consequent vitamin B12 deficiency may occur. Pernicious anaemia has a multifaceted nature. This is because vitamin B12 plays a pivotal role in the pathophysiology of the disease and, when deficient, may lead to several dysfunctions, hence the proteiform clinical presentations of pernicious anaemia. Vitamin B12 deficiency, which is also known as cobalamin deficiency, aggravates many other haematological conditions, such as myelodysplastic syndrome, acute leukemia sideroblastic anaemias, bone marrow failure states, and thromboembolism.2

The body's betrayal: mechanisms underlying pernicious anaemia

The term “pernicious anaemia” is an anachronism, dating from the era when treatment had not yet been discovered and the disease was fatal, but this name remains in use to refer to an autoimmune disorder that affects the gastric mucosa's production of intrinsic factor, leading to vitamin B12 deficiency and megaloblastic anaemia. Impaired intrinsic factor production in pernicious anaemia occurs because of autoimmune destruction of the parietal cells which secrete intrinsic factors, or the development of auto-antibodies targeted against intrinsic factors itself. Apart from impaired intrinsic factor production, other factors that contribute in the pathophysiology of pernicious anaemia are folic acid deficiency, altered pH in the small intestine, and lack of absorption of vitamin B12 complexes in the terminal ileum. This disease must therefore be differentiated from other disorders that hinder the absorption of vitamin B12.

Prevalence worldwide

According to an article published in The Nutrients, the worldwide prevalence of pernicious anaemia is 0.1%, but this rises to 2 to 3% in people over 65 years, and the female: male ratio is 2:1. It is rare in individuals under the age of 30 (2). Pernicious anaemia is prevalent across all continents. It ranges from 50 to 4,000 cases per 100,000 persons, depending on the diagnostic criteria. However, the complexity of the diagnosis leads to a miscalculation of this prevalence.3

Causes and risk factors

Explore the underlying causes of pernicious anaemia

Pernicious anaemia results from a deficiency of intrinsic factors. This deficiency is a consequence of autoimmune atrophic gastritis (antibodies attacking healthy stomach cells), leading to the injury of gastric mucosa and ultimately causing the loss of parietal cells, which normally produce hydrochloric acid and intrinsic factors. Intrinsic factors secreted by the parietal cells are needed for the absorption of vitamin B12. This vitamin deficiency ultimately leads to megaloblastic anaemia. However, due to acid loss, iron deficiency anaemia precedes cobalamin-deficient pernicious anaemia for many years.4

Identify potential risk factors

Pernicious anaemia associated with gastric atrophy is also considered an outcome of chronic Helicobacter pylori infection, however, there are conflicting views about the relationship between pernicious anaemia and Helicobacter pylori. Helicobacter invades the gastric mucosa and causes the destruction of gastric parietal cells, and atrophic gastritis comprises the availability of intrinsic factors for vitamin B12 transport and absorption, leading to vitamin B12 deficiency.

Familial predisposition has also been mentioned in the literature as far as the potential risk factors are concerned. A familial link with ≤19% of the patients having a family member with pernicious anaemia.5

Symptoms and signs

Clinical presentation progresses gradually, and patients usually show the following symptoms6


  • Pallor
  • Fatigue
  • Tachycardia
  • Lack of Mental concentration.

Involvement of small-bowel epithelium may lead to

  • Malabsorption and diarrhoea, leading to weight loss
  • Anorexia 
  • Glossitis – a frequent sign of megaloblastic anaemia, with the patient displaying a painful, smooth, red tongue

Other symptoms include


The progression of pernicious anaemia is often devious. Alternatively, patients may have no anaemic symptoms since they become accustomed to the subtle nature of the disease. There is a possibility that the underlying disease may be missed, causing a delay in the treatment unless a complete blood count is investigated.6 Following workup is suggested.

Initial serology

  • Complete blood count (CBC) showing macrocytosis
  • Vitamin B12 level
  • Folate level, (to rule out folic acid deficiency anaemia)
  • Serum iron, total iron-binding capacity and ferritin
  • Peripheral blood smear including reticulocyte count
  • Serum methylmalonic acid (elevated mainly in cobalamin deficiency) and serum homocysteine, (elevated in both cobalamin and folic acid deficiencies) help determine the cause of this type of anaemia.7

Follow-up serology

Anti-intrinsic factor antibodies are highly sensitive in detecting pernicious anaemia, and these rise with progression of disease. Antiparietal cell antibodies are less specific than anti-intrinsic factor antibodies.

  • Endoscopy and biopsies

According to the American Gastroenterological Association, patients with a new pernicious anaemia should undergo endoscopy with biopsies to confirm atrophic gastritis for risk stratification and to rule out gastric neoplasia.8

A serum cobalamin of <200 ng/L plus the presence of anti-IF antibodies confirms a diagnosis of pernicious anaemia.9


  • With long-standing pernicious anaemia, people may experience gastric polyps 
  • They are also more likely to develop gastric cancer and gastric carcinoid tumour.10
  • People with pernicious anaemia are more likely to have fractures in the back, leg, and forearm.
  • Peripheral neuropathy is an early neurological manifestation of pernicious anaemia.5 Brain and nervous system problems, muscle weakness, numbness or tingling in your hands and feet, memory loss and dementia may be permanent if treatment is delayed.11 

Treatment and management

Vitamin B12 supplementation

Intramuscular injections 

Regular intramuscular injections of vitamin B12 (hydroxocobalamin or cyanocobalamin) is the most common and effective treatment for pernicious anaemia. These injections bypass the need for intrinsic factor and directly supply the body with B12.12

Oral supplements

In some cases, high-dose oral B12 supplements may be prescribed for individuals with mild deficiencies or for maintenance therapy after initial injections.

Lifestyle and dietary changes

Dietary modifications

Patients should take a diet rich in B12 including fish, eggs, meat and dairy products. B12-fortified foods or supplements are essential for those following a vegetarian or vegan diet.

Avoidance of alcohol

Alcohol can interfere with B12 absorption. Patients should limit alcohol intake or abstain completely.

Monitoring and follow-up

Regular blood tests 

Periodic blood tests to monitor B12 levels and haematological parameters are essential to ensure the effectiveness of treatment.

Clinical follow-up

Regular check-ups with a healthcare provider to monitor symptoms, overall health, and response to treatment.

Treatment of underlying cause

Intravenous B12 therapy

In severe cases or when oral or intramuscular treatments are not well-absorbed, intravenous B12 therapy may be necessary.

Management of autoimmune condition

If pernicious anaemia is caused by an autoimmune reaction, immunosuppressive therapy may be considered under the guidance of a specialist.

Complications management

Neurological complications: 

People with advanced neurological symptoms should manage with additional treatments like physical therapies.

Gastric conditions: 

If there are concurrent gastric conditions (such as atrophic gastritis), they need to be managed properly. Patients should be made aware about the long-term outcome in the form of gastric cancer and should be educated about symptoms and screening of gastric cancer.

It's crucial for individuals diagnosed with pernicious anaemia to follow the prescribed treatment plan and attend regular follow-up appointments with their healthcare provider. Compliance with treatment and monitoring can help manage the condition effectively and improve the patient's quality of life. Patients should always consult their healthcare provider for personalized advice and treatment.


What is the main cause of pernicious anaemia?

The main cause of pernicious anaemia is a lack of intrinsic factor, a protein needed for the absorption of vitamin B12 in the digestive system. This deficiency leads to reduced B12 absorption and subsequent anaemia.

What is pernicious anaemia vs iron deficiency anaemia?

Pernicious anaemia is a specific type of megaloblastic anaemia caused by a lack of intrinsic factor, while iron deficiency anaemia is a different type of anaemia resulting from insufficient iron in the body. Both can cause similar symptoms, such as fatigue and weakness, but they have distinct underlying causes.

What tests confirm pernicious anaemia?

Tests to confirm pernicious anaemia typically involve measuring blood levels of vitamin B12, as well as checking for the presence of antibodies against intrinsic factors. In some cases, bone marrow aspiration may be performed to examine the blood cell production in the bone marrow.

What is the difference between pernicious anaemia and B12 deficiency?

Pernicious anaemia is a type of B12 deficiency, but not all B12 deficiencies are pernicious anaemia. Pernicious anaemia specifically results from a lack of intrinsic factor, which is needed for B12 absorption. Other B12 deficiencies can be caused by factors such as dietary insufficiency or malabsorption unrelated to intrinsic factor deficiency


Pernicious anaemia is an autoimmune disorder which is characterized by atrophy of gastric mucous and deficiency of intrinsic factor and vitamin B12. Pernicious anaemia is an autoimmune disease leading to the non-availability of intrinsic factors, however, it is also linked to long-standing Helicobacter pylori infection. It may not be diagnosed for long periods of time, but when clinically evident it shows symptoms of anaemia, such as pallor, fatigue and breathlessness. Other symptoms may include diarrhoea, glossitis and dyspepsia. Its diagnosis depends upon blood work mostly and includes tests like complete blood count, serum ferritin level, folic acid level, peripheral blood smear, serum methylmalonic acid and serum homocysteine. Its management depends upon replenishing vitamin B12 orally and intramuscularly, and through dietary modifications. 


  1. Vaqar S, Shackelford K. Pernicious anaemia.  StatPearls [Internet]: StatPearls Publishing; 2023. https://www.ncbi.nlm.nih.gov/books/NBK540989/
  2. Esposito G, Dottori L, Pivetta G, Ligato I, Dilaghi E, Lahner E. Pernicious anaemia: the hematological presentation of a multifaceted disorder caused by Cobalamin deficiency. Nutrients. 2022;14(8):1672. https://pubmed.ncbi.nlm.nih.gov/35458234/
  3. Stabler SP. Vitamin B12 deficiency. New England Journal of Medicine. 2013;368(2):149-60. https://www.nejm.org/doi/full/10.1056/nejmcp1113996
  4. Guéant J-L, Guéant-Rodriguez R-M, Alpers DH. Vitamin B12 absorption and malabsorption.  Vitamins and hormones. 119: Elsevier; 2022. p. 241-74. https://www.sciencedirect.com/science/article/abs/pii/S0083672922000164
  5. Ammouri W, Adnaoui¹ M. Pernicious Anaemia: Mechanisms, Diagnosis, and Management. HEMATOLOGY. 2020. 
  6. Htut TW, Thein KZ, Oo TH. Pernicious anaemia: Pathophysiology and diagnostic difficulties. Journal of Evidence‐Based Medicine. 2021;14(2):161-9. https://onlinelibrary.wiley.com/doi/abs/10.1111/jebm.12435?casa_token=EbCo6YOc96gAAAAA:IKKYRYO2kcU49NxeRACIhxiafC1BjuNVnXsLhyIZnHAtoAOw6gQDOni25UjETHiybAHP3rxD_VcvlXKdRQ
  7. VS MS. SEMINAR ON anaemia. 2022.
  8. Shah SC, Piazuelo MB, Kuipers EJ, Li D. AGA clinical practice update on the diagnosis and management of atrophic gastritis: expert review. Gastroenterology. 2021;161(4):1325-32. E7. https://www.sciencedirect.com/science/article/pii/S0016508521032364
  9. Tun AM, Thein KZ, Myint ZW, Oo TH. Pernicious anemia: Fundamental and practical aspects in diagnosis. Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Cardiovascular & Hematological Agents). 2017;15(1):17-22.
  10. Murphy G, Dawsey SM, Engels EA, Ricker W, Parsons R, Etemadi A, et al. Cancer risk after pernicious anemia in the US elderly population. Clinical Gastroenterology and Hepatology. 2015;13(13):2282-9. e4.
  11. da Silva EB, Bastos CS. Effects of vitamin B12 deficiency on the central nervous system. J Pathol Res Rev Rep SRC/JPR-152. 2022;140:2-4.
  12. Tuğba-Kartal A, Çağla-Mutlu Z. Comparison of sublingual and intramuscular administration of vitamin B12 for the treatment of vitamin B12 deficiency in children. Revista de investigación clínica. 2020;72(6):380-5. https://www.scielo.org.mx/scielo.php?pid=S0034-83762020000600380&script=sci_arttext

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Shazia Asim

PhD Scholar (Pharmacology), University of Health Sciences Lahore, Pakistan

I have extensive experience of teaching Pharmacology at an undergraduate medical institute in Lahore, Pakistan. I mentor my students by nurturing their curiosity and encouraging them to know this subject through interactive discussions. I also like to guide my students in research projects and learn pharmacology through real world application of pharmacological principles.

During my MPhil, my keen interest in research work on Aloe vera plant extract and its effect on urinary tract infection got me a gold medal. Currently, I am enrolled at the University of Health Sciences, Lahore as a Ph.D. scholar. Other than my profession and my research work, I get immense satisfaction in writing. I am an avid writer and contribute insightful articles to medical journals and mainstream newspapers, both local and international. I am a strong advocate of preventive health care and my mission is to empower individuals with knowledge that encourages them to take charge of their wellbeing.

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