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Pernicious Anemia

What It Is, Causes, Signs, Symptoms, and More

Author: Ashley Mauldin, MSN, APRN, FNP-BC

Editors: Alyssa Haag, Emily Miao, PharmD

Illustrator: Jillian Dunbar

Copyeditor: Sadia Zaman, MBBS, BSc


What is pernicious anemia?

Pernicious anemia is a condition in which the body does not have enough healthy red blood cells due to insufficient vitamin B12. Vitamin B12, also known as cobalamin, is a nutrient required for the synthesis of healthy red blood cells. Vitamin B12 is typically found in foods originating from animals, such as fish, meat, poultry, eggs, and some dairy products. 

Pernicious anemia is considered to be a type of megaloblastic anemia, which is characterized by the production of large, atypical, immature red blood cells by the bone marrow. A lack of folic acid, or vitamin B9, is another common cause of megaloblastic anemias. 

What causes pernicious anemia?

Pernicious anemia is caused by the body’s inability to absorb vitamin B12 from the small intestine, due to a lack of a protein called intrinsic factor. Intrinsic factor is a protein that can bind to cobalamin and facilitates its absorption into the body. Intrinsic factor is directly released by parietal cells in the stomach, and so a lack of intrinsic factor directly inhibits the small intestine from properly absorbing vitamin B12 from food. As a result, the body is unable to create a sufficient number of healthy red blood cells. A lack of intrinsic factor can be caused by the autoimmune destruction of gastric parietal cells, intrinsic factor itself, or both. 

Pernicious anemia is more common in those individuals who have a family history of pernicious anemia, as well as those of northern European descent. Other common causes of a vitamin B12 deficiency anemia can include chronic gastritis; taking certain medications, like antacids or metformin; following a strict vegetarian diet; and gastric surgery that removes or bypasses part of the small intestine. 

Individuals with certain autoimmune diseases, such as Addison disease, Graves disease, hypoparathyroidism, hypothyroidism, type 1 diabetes, vitiligo, and celiac disease can also increase their risk of developing pernicious anemia

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Is pernicious anemia an autoimmune disease?

Pernicious anemia can also be considered an autoimmune condition. In certain individuals, the body’s immune system either directly attacks protein intrinsic factor, or it may attack the cells that are responsible for producing intrinsic factor (i.e., the parietal cells that line the stomach). Either way, a lack of protein intrinsic factor results in an impaired ability to absorb and utilize vitamin B12. 

What are the signs and symptoms of pernicious anemia?

Signs and symptoms of pernicious anemia can include paleness of the skin and mucous membranes, general weakness, fatigue, nausea, vomiting, glossitis (i.e., a swollen tongue), and a loss of appetite. Individuals who have experienced a low vitamin B12 level for a long time may present with signs and symptoms of nervous system damage which can include short-term memory loss, confusion, depression, imbalance, irritability, as well as numbness and tingling in the hands and feet. Individuals with severe pernicious anemia will usually present with shortness of breath, dizziness, and tachycardia.

How is pernicious anemia diagnosed?

Pernicious anemia diagnosis is based on medical and family history, physical examination, and a variety of blood tests. The healthcare provider will typically check a complete blood cell count blood test (CBC), which measures the amount of hemoglobin and hematocrit in the blood. A decreased level of both hemoglobin and hematocrit typically indicates that anemia is present. However, since there are several different types of anemia, other blood tests are conducted to distinguish the exact type of anemia. These blood tests can include a reticulocyte (i.e., immature red blood cells) count, peripheral blood smear, folate levels, iron levels, total iron-binding capacity, vitamin B12 levels, as well as auto-antibody presence in the blood. 

How is pernicious anemia treated?

Treatment for pernicious anemia depends on the underlying cause, but generally includes interventions that are aimed at increasing the vitamin B12 level in the body. Therefore, treatment usually consists of either oral or intramuscular vitamin B12 supplements depending on the severity of the pernicious anemia. Some individuals may only require vitamin B12 supplements, and advice to start eating foods high in B12. In some cases, daily, weekly, or monthly intramuscular injections of vitamin B12 may be required. 

What are the most important facts to know about pernicious anemia?

Pernicious anemia is a condition where there is an insufficient number of healthy red blood cells due to a lack of vitamin B12. Vitamin B12 is a type of nutrient that the body needs to properly make healthy red blood cells and is usually found in foods originating from animals (e.g., fish and poultry). Pernicious anemia is considered to be a type of megaloblastic anemia, which is characterized by unusually large, abnormal, immature red blood cells. Pernicious anemia is caused by an inability of the body to absorb vitamin B12 from the small intestine due to a lack of a protein called intrinsic factor due to autoimmune destruction. Common causes of vitamin B12 deficiency anemia include chronic gastritis; following a strict vegetarian or vegan diet; taking certain medications, like antacids or metformin; as well as gastric surgery that removes or bypasses part of the small intestine. Pernicious anemia can be considered an autoimmune condition. Signs and symptoms of pernicious anemia are indicative of a vitamin B12 deficiency and can include paleness of the skin and mucous membranes; weakness; fatigue; nausea; vomiting; and a loss of appetite. Pernicious anemia is diagnosed based on a thorough medical history and subsequent blood tests. The treatment for pernicious anemia depends on the underlying cause, but generally includes interventions that are aimed at increasing the vitamin B12 level in the body (e.g., oral or injectable vitamin B12 supplements depending on the severity of the pernicious anemia).

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Related links

Macrocytic anemia: Pathology review
Megaloblastic anemia
Vitamin B12 Deficiency
Anemia: Clinical Practice

Resources for research and reference

Johns Hopkins Medicine. (2021). Vitamin B12 deficiency anemia. In John Hopkins Medicine: Health. Retrieved October 29, 2021, from https://www.hopkinsmedicine.org/health/conditions-and-diseases/vitamin-B12-deficiency-anemia

Johnson, L. (2021). Vitamin B12 deficiency - Disorders of Nutrition. In Merck Manual: Consumer Version. Retrieved October 29, 2021, from https://www.merckmanuals.com/home/disorders-of-nutrition/vitamins/vitamin-B12-deficiency

Mayo Clinic Staff. (2021). Vitamin B-12. In Mayo Clinic. Retrieved October 29, 2021, from https://www.mayoclinic.org/drugs-supplements-vitamin-B12/art-20363663

National Heart, Lung, and Blood Institute (NHLBI). (2021). Pernicious Anemia. In National Heart, Lung, and Blood Institute (NHLBI). Retrieved October 29, 2021, from https://www.nhlbi.nih.gov/health-topics/pernicious-anemia

National Library of Medicine (NLM). (2021). Pernicious anemia. In MedlinePlus: Medical Encyclopedia. Retrieved October 29, 2021, from https://medlineplus.gov/ency/article/000569.htm

National Organization for Rare Disorders. (2021). Anemia, Megaloblastic. In National Organization for Rare Disorders (NORD). Retrieved October 29, 2021, from https://rarediseases.org/rare-diseases/anemia-megaloblastic/

National Organization for Rare Disorders. (2021). Anemia, Pernicious. In National Organization for Rare Disorders (NORD). Retrieved October 29, 2021, from https://rarediseases.org/rare-diseases/anemia-pernicious/#:~:text=Pernicious%20anemia%20is%20a%20rare,vitamin%20B12%20cannot%20be%20absorbed.

National Institutes of Health Office of Dietary Supplements. (2021). Vitamin B12. In National Institutes of Health Office of Dietary Supplements. Retrieved November 22, 2021, from https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/. 

Rodriguez, N. M., Shackelford, K. (2021). Pernicious Anemia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing LLC. Available from: https://www.ncbi.nlm.nih.gov/books/NBK540989/