In the anemias caused by deficiencies of vitamin B12 or folic acid, identical bone marrow and peripheral blood changes occur, because both vitamins are essential for normal DNA synthesis. In either anemia, the RBCs that are produced are abnormally large and are called megaloblastic RBCs. Other cells derived from the myeloid stem cell (nonlymphoid WBCs, platelets) are also abnor mal. A bone marrow analysis reveals hyperplasia (abnormal in-crease in the number of cells), and the precursor erythroid and myeloid cells are large and bizarre in appearance. Many of these abnormal RBCs and myeloid cells are destroyed within the mar-row, however, so the mature cells that do leave the marrow are ac-tually fewer in number. Thus, pancytopenia (a decrease in all myeloid-derived cells) can develop. In an advanced situation, the hemoglobin value may be as low as 4 to 5 g/dL, the WBC count 2,000 to 3,000/mm3, and the platelet count less than 50,000/mm3. Those cells that are released into the circulation are often abnormally shaped. The neutrophils are hypersegmented. The platelets may be abnormally large. The RBCs are abnormally shaped, and the shapes may vary widely (poikilocytosis). Because the RBCs are very large, the MCV is very high, usually exceeding 110 μ m3.
Folic acid, a vitamin that is necessary for normal RBC produc-tion, is stored as compounds referred to as folates. The folate stores in the body are much smaller than those of vitamin B12, and they are quickly depleted when the dietary intake of folate is deficient (within 4 months). Folate is found in green vegeta-bles and liver. Folate deficiency occurs in people who rarely eat uncooked vegetables. Alcohol increases folic acid requirements, and, at the same time, patients with alcoholism usually have a diet that is deficient in the vitamin. Folic acid requirements are also increased in patients with chronic hemolytic anemias and in women who are pregnant, because the need for RBC production is increased in these conditions. Some patients with malabsorp-tive diseases of the small bowel, such as sprue, may not absorb folic acid normally.
A deficiency of vitamin B12 can occur in several ways. Inadequate dietary intake is rare but can develop in strict vegetarians who consume no meat or dairy products. Faulty absorption from the gastrointestinal tract is more common. This occurs in conditions such as Crohn’s disease, or after ileal resection or gastrectomy. Another cause is the absence of intrinsic factor, as in pernicious anemia. Intrinsic factor is normally secreted by cells within the gastric mucosa; normally it binds with the dietary vitamin B12 and travels with it to the ileum, where the vitamin is absorbed. With-out intrinsic factor, orally consumed vitamin B12 cannot be ab-sorbed, and RBC production is eventually diminished. Even if adequate vitamin B12 and intrinsic factor are present, a deficiency may occur if disease involving the ileum or pancreas impairs ab-sorption. Pernicious anemia, which tends to run in families, is primarily a disorder of adults, particularly the elderly. The ab-normality is in the gastric mucosa: the stomach wall atrophies and fails to secrete intrinsic factor. Therefore, the absorption of vita-min B12 is significantly impaired.
The body normally has large stores of vitamin B12, so years may pass before the deficiency results in anemia. Because the body compensates so well, the anemia can be severe before the patient becomes symptomatic. For unknown reasons, patients with pernicious anemia have a higher incidence of gastric cancer than the general population; these patients should have endos-copies at regular intervals (every 1 to 2 years) to screen for early gastric cancer.
Symptoms of folic acid and vitamin B12 deficiencies are similar, and the two anemias may coexist. However, the neurologic man-ifestations of vitamin B12 deficiency do not occur with folic acid deficiency, and they persist if B12 is not replaced. Therefore, care-ful distinction between the two anemias must be made. Serum lev-els of both vitamins can be measured. In the case of folic acid deficiency, even small amounts of folate will increase the serum fo-late level, sometimes to normal. Measuring the amount of folate within the RBC itself (red cell folate) is therefore a more sensitive test in determining true folate deficiency.
After the body stores of vitamin B12 are depleted, patients may begin to show signs of the anemia. However, because the onset and progression of the anemia are so gradual, the body can compensate very well until the anemia is severe, so that the typical manifesta-tions of anemia (weakness, listlessness, fatigue) may not be appar-ent initially. The hematologic effects of deficiency are accompanied by effects on other organ systems, particularly the gastrointestinal tract and nervous system. Patients with pernicious anemia develop a smooth, sore, red tongue and mild diarrhea. They are extremely pale, particularly in the mucous membranes. They may become confused; more often they have paresthesias in the extremities (par-ticularly numbness and tingling in the feet and lower legs). They may have difficulty maintaining their balance because of damage to the spinal cord, and they also lose position sense (propriocep-tion). These symptoms are progressive, although the course of illness may be marked by spontaneous partial remissions and exac-erbations. Without treatment, patients can die after several years, usually from heart failure secondary to anemia.
The classic method of determining the cause of vitamin B12 defi-ciency is the Schilling test, in which the patient receives a small oral dose of radioactive vitamin B12, followed in a few hours by a large, nonradioactive parenteral dose of vitamin B12 (this aids in renal ex-cretion of the radioactive dose). If the oral vitamin is absorbed, more than 8% will be excreted in the urine within 24 hours; there-fore, if no radioactivity is present in the urine (ie, the radioactive vitamin B12 stays within the gastrointestinal tract), the cause is gastrointestinal malabsorption of the vitamin B12. Conversely, if the urine is radioactive, the cause of the deficiency is not ileal dis-ease or pernicious anemia. Later, the same procedure is repeated, but this time intrinsic factor is added to the oral radioactive vita-min B12. If radioactivity is now detected in the urine (ie, the B12 was absorbed from the gastrointestinal tract in the presence of intrinsic factor), the diagnosis of pernicious anemia can be made. The Schilling test is useful only if the urine collections are complete; therefore, the nurse must promote the patient’s understanding and ability to comply with this collection.
Another useful, easier test is the intrinsic factor antibody test. A positive test indicates the presence of antibodies that bind the vit-amin B12–intrinsic factor complex and prevent it from binding to receptors in the ileum, thus preventing its absorption. Unfortu-nately, this test is not specific for pernicious anemia alone, but it can aid in the diagnosis.
Folate deficiency is treated by increasing the amount of folic acid in the diet and administering 1 mg of folic acid daily. Folic acid is administered intramuscularly only for people with malabsorption problems. With the exception of the vitamins adminis-tered during pregnancy, most proprietary vitamin preparations do not contain folic acid, so it must be administered as a sepa-rate tablet. After the hemoglobin level returns to normal, the folic acid replacement can be stopped. However, patients with alcoholism should continue receiving folic acid as long as they continue alcohol consumption.
Vitamin B12 deficiency is treated by vitamin B12 replacement. Vegetarians can prevent or treat deficiency with oral supplements through vitamins or fortified soy milk. When, as is more common, the deficiency is due to defective absorption or absence of intrin-sic factor, replacement is by monthly intramuscular injections of vitamin B12, usually at a dose of 1000 μ g. The reticulocyte count rises within 1 week, and in several weeks the blood counts are all normal. The tongue improves in several days. However, the neu-rologic manifestations require more time for recovery; if there is severe neuropathy, the patient may never recover fully. To prevent recurrence of pernicious anemia, vitamin B12 therapy must be con-tinued for life.
Assessment of patients who have or are at risk for megaloblastic anemia includes inspection of the skin and mucous membranes. Mild jaundice may be apparent and is best seen in the sclera with-out using fluorescent lights. Vitiligo (patchy loss of skin pigmen-tation) and premature graying of the hair are often seen in patients with pernicious anemia. The tongue is smooth, red, and sore. Be-cause of the neurologic complications associated with these ane-mias, a careful neurologic assessment is important, including tests of position and vibration sense.
The nurse needs to pay particular attention to ambulation and should assess the patient’s gait and stability as well as the need for assistive devices (eg, canes, walkers) and for assistance in manag-ing daily activities. Of particular concern is ensuring safety when position sense, coordination, and gait are affected. Physical and occupational therapy referrals may be needed.
If sensation is altered, patients need to be instructed to avoid excessive heat and cold.
Because mouth and tongue soreness may restrict nutritional in-take, the nurse can advise patients and families to prepare bland, soft foods and to eat small amounts frequently. The nurse also may explain that other nutritional deficiencies, such as alcohol-induced anemia, can induce neurologic problems.
Patients must also be taught about the chronicity of their dis-order and the necessity for monthly vitamin B12 injections even in the absence of symptoms. Many patients can be instructed to self-administer their injections. The gastric atrophy associated with pernicious anemia increases the risk of gastric carcinoma, so these patients need to understand that ongoing medical follow-up and screening are important.