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What Is Pernicious Anemia?

Pernicious anemia (per-NISH-us uh-NEE-me-uh) is a condition in which the body can't make enough healthy red blood cells because it doesn't have enough vitamin B12.

Vitamin B12 is a nutrient found in some foods. The body needs this nutrient to make healthy red blood cells and to keep its nervous system working properly.

People who have pernicious anemia can't absorb enough vitamin B12 from food. This is because they lack intrinsic (in-TRIN-sik) factor, a protein made in the stomach. A lack of this protein leads to vitamin B12 deficiency.

Other conditions and factors also can cause vitamin B12 deficiency. Examples include infections, surgery, medicines, and diet. Technically, the term "pernicious anemia" refers to vitamin B12 deficiency due to a lack of intrinsic factor. Often though, vitamin B12 deficiency due to other causes also is called pernicious anemia.

This article discusses pernicious anemia due to a lack of intrinsic factor and other causes.

Overview

Pernicious anemia is a type of anemia. The term "anemia" usually refers to a condition in which the blood has a lower than normal number of red blood cells. In pernicious anemia, the body can't make enough healthy red blood cells because it doesn't have enough vitamin B12.

Without enough vitamin B12, your red blood cells don't divide normally and are too large. They may have trouble getting out of the bone marrow—a sponge-like tissue inside the bones where blood cells are made.

Without enough red blood cells to carry oxygen to your body, you may feel tired and weak. Severe or long-lasting pernicious anemia can damage the heart, brain, and other organs in the body.

Pernicious anemia also can cause other problems, such as nerve damage, neurological problems (such as memory loss), and digestive tract problems. People who have pernicious anemia also may be at higher risk for weakened bone strength and stomach cancer.

Outlook

The term “pernicious” means “deadly.”  The condition is called pernicious anemia because it often was fatal in the past, before vitamin B12 treatments were available. Now, pernicious anemia usually is easy to treat with vitamin B12 pills or shots.

With ongoing care and proper treatment, most people who have pernicious anemia can recover, feel well, and live normal lives.

Without treatment, pernicious anemia can lead to serious problems with the heart, nerves, and other parts of the body. Some of these problems may be permanent.




Other Names for Pernicious Anemia

Pernicious anemia is one of two major types of "macrocytic" or "megaloblastic" anemia. These terms refer to anemia in which the red blood cells are larger than normal. (The other major type of macrocytic anemia is caused by folic acid deficiency.)

Rarely, children are born with an inherited disorder that prevents their bodies from making intrinsic factor. This disorder is called congenital pernicious anemia.

Vitamin B12 deficiency also is called cobalamin deficiency and combined systems disease.




What Causes Pernicious Anemia?

Pernicious anemia is caused by a lack of intrinsic factor or other causes, such as infections, surgery, medicines, or diet.

Lack of Intrinsic Factor

Intrinsic factor is a protein made in the stomach. It helps your body absorb vitamin B12. In some people, an autoimmune response causes a lack of intrinsic factor.

An autoimmune response occurs if the body’s immune system makes antibodies (proteins) that mistakenly attack and damage the body's tissues or cells.

In pernicious anemia, the body makes antibodies that attack and destroy the parietal (pa-RI-eh-tal) cells. These cells line the stomach and make intrinsic factor. Why this autoimmune response occurs isn't known.

As a result of this attack, the stomach stops making intrinsic factor. Without intrinsic factor, your body can't move vitamin B12 through the small intestine, where it's absorbed. This leads to vitamin B12 deficiency.

A lack of intrinsic factor also can occur if you've had part or all of your stomach surgically removed. This type of surgery reduces the number of parietal cells available to make intrinsic factor.

Rarely, children are born with an inherited disorder that prevents their bodies from making intrinsic factor. This disorder is called congenital pernicious anemia.

Other Causes

Pernicious anemia also has other causes, besides a lack of intrinsic factor. Malabsorption in the small intestine and a diet lacking vitamin B12 both can lead to pernicious anemia.

Malabsorption in the Small Intestine

Sometimes pernicious anemia occurs because the body's small intestine can't properly absorb vitamin B12. This may be the result of:

  • Too many of the wrong kind of bacteria in the small intestine. This is a common cause of pernicious anemia in older adults. The bacteria use up the available vitamin B12 before the small intestine can absorb it.
  • Diseases that interfere with vitamin B12 absorption. One example is celiac disease. This is a genetic disorder in which your body can't tolerate a protein called gluten. Another example is Crohn's disease, an inflammatory bowel disease. HIV also may interfere with vitamin B12 absorption.
  • Certain medicines that alter bacterial growth or prevent the small intestine from properly absorbing vitamin B12. Examples include antibiotics and certain diabetes and seizure medicines.
  • Surgical removal of part or all of the small intestine.
  • A tapeworm infection. The tapeworm feeds off of the vitamin B12. Eating undercooked, infected fish may cause this type of infection.

Diet Lacking Vitamin B12

Some people get pernicious anemia because they don't have enough vitamin B12 in their diets. This cause of pernicious anemia is less common than other causes.

Good food sources of vitamin B12 include:

  • Breakfast cereals with added vitamin B12
  • Meats such as beef, liver, poultry, and fish
  • Eggs and dairy products (such as milk, yogurt, and cheese)
  • Foods fortified with vitamin B12, such as soy-based beverages and vegetarian burgers

Strict vegetarians who don't eat any animal or dairy products and don't take a vitamin B12 supplement are at risk for pernicious anemia.

Breastfed infants of strict vegetarian mothers also are at risk for pernicious anemia. These infants can develop anemia within months of being born. This is because they haven't had enough time to store vitamin B12 in their bodies. Doctors treat these infants with vitamin B12 supplements.

Other groups, such as the elderly and people who suffer from alcoholism, also may be at risk for pernicious anemia. These people may not get the proper nutrients in their diets.




Who Is at Risk for Pernicious Anemia?

Pernicious anemia is more common in people of Northern European and African descent than in other ethnic groups.

Older people also are at higher risk for the condition. This is mainly due to a lack of stomach acid and intrinsic factor, which prevents the small intestine from absorbing vitamin B12. As people grow older, they tend to make less stomach acid.

Pernicious anemia also can occur in younger people and other populations. You're at higher risk for pernicious anemia if you:

  • Have a family history of the condition.
  • Have had part or all of your stomach surgically removed. The stomach makes intrinsic factor. This protein helps your body absorb vitamin B12.
  • Have an autoimmune disorder that involves the endocrine glands, such as Addison's disease, type 1 diabetes, Graves' disease, or vitiligo. Research suggests a link may exist between these autoimmune disorders and pernicious anemia that's caused by an autoimmune response.
  • Have had part or all of your small intestine surgically removed. The small intestine is where vitamin B12 is absorbed.
  • Have certain intestinal diseases or other disorders that may prevent your body from properly absorbing vitamin B12. Examples include Crohn's disease, intestinal infections, and HIV.
  • Take medicines that prevent your body from properly absorbing vitamin B12. Examples of such medicines include antibiotics and certain seizure medicines.
  • Are a strict vegetarian who doesn't eat any animal or dairy products and doesn't take a vitamin B12 supplement, or if you eat poorly overall.



What Are the Signs and Symptoms of Pernicious Anemia?

A lack of vitamin B12 (vitamin B12 deficiency) causes the signs and symptoms of pernicious anemia. Without enough vitamin B12, your body can't make enough healthy red blood cells, which causes anemia.

Some of the signs and symptoms of pernicious anemia apply to all types of anemia. Other signs and symptoms are specific to a lack of vitamin B12.

Signs and Symptoms of Anemia

The most common symptom of all types of anemia is fatigue (tiredness). Fatigue occurs because your body doesn’t have enough red blood cells to carry oxygen to its various parts.

A low red blood cell count also can cause shortness of breath, dizziness, headache, coldness in your hands and feet, pale or yellowish skin, and chest pain.

A lack of red blood cells also means that your heart has to work harder to move oxygen-rich blood through your body. This can lead to irregular heartbeats called arrhythmias (ah-RITH-me-ahs), heart murmur, an enlarged heart, or even heart failure.

Signs and Symptoms of Vitamin B12 Deficiency

Vitamin B12 deficiency may lead to nerve damage. This can cause tingling and numbness in your hands and feet, muscle weakness, and loss of reflexes. You also may feel unsteady, lose your balance, and have trouble walking. Vitamin B12 deficiency can cause weakened bones and may lead to hip fractures.

Severe vitamin B12 deficiency can cause neurological problems, such as confusion, dementia, depression, and memory loss.

Other symptoms of vitamin B12 deficiency involve the digestive tract. These symptoms include nausea (feeling sick to your stomach) and vomiting, heartburn, abdominal bloating and gas, constipation or diarrhea, loss of appetite, and weight loss. An enlarged liver is another symptom.

A smooth, thick, red tongue also is a sign of vitamin B12 deficiency and pernicious anemia.

Infants who have vitamin B12 deficiency may have poor reflexes or unusual movements, such as face tremors. They may have trouble feeding due to tongue and throat problems. They also may be irritable. If vitamin B12 deficiency isn't treated, these infants may have permanent growth problems.




How Is Pernicious Anemia Diagnosed?

Your doctor will diagnose pernicious anemia based on your medical and family histories, a physical exam, and test results.

Your doctor will want to find out whether the condition is due to a lack of intrinsic factor or another cause. He or she also will want to find out the severity of the condition, so it can be properly treated.

Specialists Involved

Primary care doctors—such as family doctors, internists, and pediatricians (doctors who treat children)—often diagnose and treat pernicious anemia. Other kinds of doctors also may be involved, including:

  • A neurologist (nervous system specialist)
  • A cardiologist (heart specialist)
  • A hematologist (blood disease specialist)
  • A gastroenterologist (digestive tract specialist)

Medical and Family Histories

Your doctor may ask about your signs and symptoms. He or she also may ask:

  • Whether you've had any stomach or intestinal surgeries
  • Whether you have any digestive disorders, such as celiac disease or Crohn's disease
  • About your diet and any medicines you take
  • Whether you have a family history of anemia or pernicious anemia
  • Whether you have a family history of autoimmune disorders (such as Addison's disease, type 1 diabetes, Graves' disease, or vitiligo). Research suggests a link may exist between these autoimmune disorders and pernicious anemia that's caused by an autoimmune response.

Physical Exam

During the physical exam, your doctor may check for pale or yellowish skin and an enlarged liver. He or she may listen to your heart for rapid or irregular heartbeats or a heart murmur.

Your doctor also may check for signs of nerve damage. He or she may want to see how well your muscles, eyes, senses, and reflexes work. Your doctor may ask questions or do tests to check your mental status, coordination, and ability to walk.

Diagnostic Tests and Procedures

Blood tests and procedures can help diagnose pernicious anemia and find out what's causing it.

Complete Blood Count

Often, the first test used to diagnose many types of anemia is a complete blood count (CBC). This test measures many parts of your blood. For this test, a small amount of blood is drawn from a vein (usually in your arm) using a needle.

A CBC checks your hemoglobin (HEE-muh-glow-bin) and hematocrit (hee-MAT-oh-crit) levels. Hemoglobin is an iron-rich protein that helps red blood cells carry oxygen from the lungs to the rest of the body. Hematocrit is a measure of how much space red blood cells take up in your blood. A low level of hemoglobin or hematocrit is a sign of anemia.

The normal range of these levels may be lower in certain racial and ethnic populations. Your doctor can explain your test results to you.

The CBC also checks the number of red blood cells, white blood cells, and platelets (PLATE-lets) in your blood. Abnormal results may be a sign of anemia, another blood disorder, an infection, or another condition.

Finally, the CBC looks at mean corpuscular (kor-PUS-kyu-lar) volume (MCV). MCV is a measure of the average size of your red blood cells. MCV can be a clue as to what's causing your anemia. In pernicious anemia, the red blood cells are larger than normal.

Other Blood Tests

If the CBC results confirm that you have anemia, you may need other blood tests to find out what type of anemia you have.

A reticulocyte (re-TIK-u-lo-site) count measures the number of young red blood cells in your blood. The test shows whether your bone marrow is making red blood cells at the correct rate. People who have pernicious anemia have low reticulocyte counts.

Serum folate, iron, and iron-binding capacity tests also can help show whether you have pernicious anemia or another type of anemia.

Your doctor may recommend other blood tests to check:

  • Your vitamin B12 level. A low level of vitamin B12 in the blood indicates pernicious anemia.
  • Your homocysteine and methylmalonic acid (MMA) levels. High levels of these substances in your body are a sign of pernicious anemia.
  • For intrinsic factor antibodies and parietal cell antibodies. These antibodies also are a sign of pernicious anemia.

Bone Marrow Tests

Bone marrow tests can show whether your bone marrow is healthy and making enough red blood cells. The two bone marrow tests are aspiration (as-pi-RA-shun) and biopsy.

For aspiration, your doctor removes a small amount of fluid bone marrow through a needle. For a biopsy, your doctor removes a small amount of bone marrow tissue through a larger needle. The samples are then examined under a microscope.

In pernicious anemia, the bone marrow cells that turn into blood cells are larger than normal.




How Is Pernicious Anemia Treated?

Doctors treat pernicious anemia by replacing the missing vitamin B12 in the body. People who have pernicious anemia may need lifelong treatment.

The goals of treating pernicious anemia include:

  • Preventing or treating the anemia and its signs and symptoms
  • Preventing or managing complications, such as heart and nerve damage
  • Treating the cause of the pernicious anemia (if a cause can be found)

Specific Types of Treatment

Pernicious anemia usually is easy to treat with vitamin B12 shots or pills.

If you have severe pernicious anemia, your doctor may recommend shots first. Shots usually are given in a muscle every day or every week until the level of vitamin B12 in your blood increases. After your vitamin B12 blood level returns to normal, you may get a shot only once a month.

For less severe pernicious anemia, your doctor may recommend large doses of vitamin B12 pills. A vitamin B12 nose gel and spray also are available. These products may be useful for people who have trouble swallowing pills, such as older people who have had strokes.

Your signs and symptoms may begin to improve within a few days after you start treatment. Your doctor may advise you to limit your physical activity until your condition improves.

If your pernicious anemia is caused by something other than a lack of intrinsic factor, you may get treatment for the cause (if a cause can be found). For example, your doctor may prescribe medicines to treat a condition that prevents your body from absorbing vitamin B12.

If medicines are the cause of your pernicious anemia, your doctor may change the type or dose of medicine you take. Infants of strict vegetarian mothers may be given vitamin B12 supplements from birth.




How Can Pernicious Anemia Be Prevented?

You can't prevent pernicious anemia caused by a lack of intrinsic factor. Without intrinsic factor, you won't be able to absorb vitamin B12 and will develop pernicious anemia.

Although uncommon, some people develop pernicious anemia because they don't get enough vitamin B12 in their diets. You can take steps to prevent pernicious anemia caused by dietary factors.

Eating foods high in vitamin B12 can help prevent low vitamin B12 levels. Good food sources of vitamin B12 include:

  • Breakfast cereals with added vitamin B12
  • Meats such as beef, liver, poultry, and fish
  • Eggs and dairy products (such as milk, yogurt, and cheese)
  • Foods fortified with vitamin B12, such as soy-based beverages and vegetarian burgers

If you’re a strict vegetarian, talk with your doctor about having your vitamin B12 level checked regularly.

Vitamin B12 also is found in multivitamins and B-complex vitamin supplements. Doctors may recommend supplements for people at risk for vitamin B12 deficiency, such as strict vegetarians or people who have had stomach surgery.

Older adults may have trouble absorbing vitamin B12. Thus, doctors may recommend that older adults eat foods fortified with vitamin B12 or take vitamin B12 supplements.




Living With Pernicious Anemia

With proper treatment, people who have pernicious anemia can recover, feel well, and live normal lives. If you have complications of pernicious anemia, such as nerve damage, early treatment may help reverse the damage.

Ongoing Care

If you have pernicious anemia, you may need lifelong treatment. See your doctor regularly for checkups and ongoing care. Take vitamin B12 supplements as your doctor advises. This may help prevent symptoms and complications.

During your followup visits, your doctor may check for signs of vitamin B12 deficiency. He or she also may adjust your treatment as needed.

If you have pernicious anemia, you're at higher risk for stomach cancer. See your doctor regularly so he or she can check for this complication.

Also, tell your family members, especially your children and brothers and sisters, that you have pernicious anemia. Pernicious anemia can run in families, so they may have a higher risk for the condition.




Clinical Trials

The National Heart, Lung, and Blood Institute (NHLBI) is strongly committed to supporting research aimed at preventing and treating heart, lung, and blood diseases and conditions and sleep disorders.

NHLBI-supported research has led to many advances in medical knowledge and care. Often, these advances depend on the willingness of volunteers to take part in clinical trials.

Clinical trials test new ways to prevent, diagnose, or treat various diseases and conditions. For example, new treatments for a disease or condition (such as medicines, medical devices, surgeries, or procedures) are tested in volunteers who have the illness. Testing shows whether a treatment is safe and effective in humans before it is made available for widespread use.

By taking part in a clinical trial, you can gain access to new treatments before they’re widely available. You also will have the support of a team of health care providers, who will likely monitor your health closely. Even if you don’t directly benefit from the results of a clinical trial, the information gathered can help others and add to scientific knowledge.

If you volunteer for a clinical trial, the research will be explained to you in detail. You’ll learn about treatments and tests you may receive, and the benefits and risks they may pose. You’ll also be given a chance to ask questions about the research. This process is called informed consent.

If you agree to take part in the trial, you’ll be asked to sign an informed consent form. This form is not a contract. You have the right to withdraw from a study at any time, for any reason. Also, you have the right to learn about new risks or findings that emerge during the trial.

For more information about clinical trials related to pernicious anemia and vitamin B12 deficiency, talk with your doctor. You also can visit the following Web sites to learn more about clinical research and to search for clinical trials:

For more information about clinical trials for children, visit the NHLBI’s Children and Clinical Studies Web page.




Links to Other Information About Pernicious Anemia

NHLBI Resources

Non-NHLBI Resources

Clinical Trials

 
April 01, 2011 Last Updated Icon

The NHLBI updates Health Topics articles on a biennial cycle based on a thorough review of research findings and new literature. The articles also are updated as needed if important new research is published. The date on each Health Topics article reflects when the content was originally posted or last revised.