Megaloblastic Anemia /
Pernicious Anemia

Alternative Names: Terms related to megaloblastic anemia include: pernicious anemia, megaloblastic anemia of pregnancy, folic acid deficiency anemia, folate deficiency anemia, vitamin B12 deficiency anemia, hypovitaminosis B12.

Megaloblastic anemias are somewhat rare blood disorders characterized by the presence of large, structurally and visually abnormal, immature red blood cells (megaloblasts).  Decreased numbers and immaturity of white blood cells (leukocytes) and blood platelets (thrombocytes) may also occur.  Megaloblastic anemias are usually caused by a deficiency or defective absorption of either vitamin B12 (cobalamin) or folic acid.  As a result, they are also known as the vitamin deficiency anemias. Folic acid was discovered in 1931 as a "cure" for the anemia of pregnancy.  Eating extra yeast also seemed to relieve the symptoms of pernicious anemia, but the neurological symptoms of this disease either were not resolved or appeared later on, confirming some doctors' feelings that there were two different problems involved.  In 1945, folic acid was isolated from spinach; we now know that B12 and folic acid produce two very similar deficiency problems.  B12 deficiency may lead to progressive and irreversible neurological damage, whereas a lack of folic acid will not.

Both vitamin B12 and folic acid are essential in the bone marrow for the production of healthy red blood cells in sufficient amounts.  If either is lacking in the diet, or if the absorption of either is impaired, megaloblastic anemia may result.  Other causes include leukemia, myelofibrosis, multiple myeloma, certain hereditary disorders, drugs that affect nucleic acid metabolism such as chemotherapy agents (methotrexate).

Incidence; Causes and Development; Contributing Risk Factors

Pernicious anemia is one of the megaloblastic anemias and can affect all racial groups, but the incidence is higher among people of Scandinavian or Northern European descent.  Pernicious anemia usually does not appear before the age of 30, although a juvenile form of the disease can occur in children and is evident before the child is 3 years old.

Folic acid deficiency anemia is more common in the Western world because many people there refuse to eat sufficient amounts of green, leafy vegetables.  Because the demand for folic acid increases among pregnant women and among patients on hemodialysis, risk becomes even higher for these people.

Pernicious anemia is caused by someone losing their ability to make intrinsic factor (IF), a substance that enables vitamin B12 to be absorbed from the intestine.  The result is vitamin B12 deficiency, which gradually affects sensory and motor nerves, causing neurological, gastrointestinal and cardiovascular problems.

Folic acid anemia occurs when folic-acid levels are low, usually due to inadequate dietary intake or faulty absorption.  In contrast to vitamin B12, the liver is able to store only a small amount of folic acid.  If the diet lacks folic acid, anemia will arise within a few months.

Folic acid deficiency is seen frequently among elderly women, especially those who have poor diets.  It usually results from a diet lacking in foods with high folic acid content, or from the body's inability to digest foods or absorb foods having high folic acid content.  Other factors that increase the risk of developing folic acid deficiency anemia are:

• age
• alcoholism
• birth-control pills, anticonvulsant therapy, sulfa antibiotics, and certain other medications
• illness
• smoking
• stress

Signs and Symptoms

Symptoms, which usually begin gradually, include loss of appetite, diarrhea, paleness, fatigue, and headache.  Tingling of the hands and feet, as well as the onset of spastic movements, may indicate that the nervous system has been affected.  Weight loss and lack of appetite (anorexia) may also occur, as well as jaundice, confusion and depression.

Lesions in the gastrointestinal tract may cause abnormal activity in the intestines and difficulties with the absorption of food.  Enlargement of liver and spleen (hepatosplenomegaly) may also occur, accompanied by yellow discoloration of the skin (jaundice) or pallor.  Weakness, heart palpitations, difficulty breathing, as well as pain in the limbs are other possible symptoms.  Mouth and tongue infection may also occur.  Neurological lesions, irritability, and abnormal feelings (e.g.  of heat and cold) may also be present.

The main symptoms of pernicious anemia are tiredness, shortness of breath and fatigue.

Fatigue is often the first sign of folic acid deficiency anemia.  Other symptoms include:

• anorexia nervosa
• pale skin
• paranoia
• rapid heart beat
• sore, inflamed tongue
• weakness
• weight loss

Diagnosis and Tests

Between 50 and 75% of patients with pernicious anemia have antibodies to IF, and 93% have antibodies to parietal cells which means this is another autoimmune disorder.  Intrinsic factor and hydrochloric acid are produced by the parietal cells in the stomach; both are needed in order to release B12 from foods.

The megaloblastic anemias of whatever sort are usually diagnosed in the course of a regular blood examination.  The large, immature red blood cells are unmistakable.  Diagnosis is confirmed through blood tests to measure hemoglobin, an iron-containing compound that carries oxygen to cells throughout the body.  Symptoms may be reevaluated after the patient has taken prescription folic acid supplements.

Treatment and Prevention

Usually, injections of vitamin B12 are sufficient to overcome the deficiency.  Persons with this form of megeloblastic anemia usually have to take the supplemental B12 for the rest of their lives.  Persons with folic acid deficiency anemia usually take supplemental folic acid by mouth daily.  This treatment, too, may go on throughout a person's life.

Alternative therapies for folic acid deficiency anemia may include reflexology concentrated on areas that influence the liver and spleen.  Increasing consumption of foods high in folate is helpful.  Eating a mixture of yogurt (8 oz) and turmeric (1 tsp) also may help resolve symptoms.

Seek medical attention if...

A doctor should be seen if fever, chills, muscle aches, or new symptoms develop during treatment, or if symptoms do not improve after two weeks of treatment.

A physician should also be contacted if the tongue becomes slick or smooth or the patient:

• bruises or tires easily
• feels ill for more than five days
• feels weak or out of breath
• looks pale or jaundiced.