Pernicious anemia

A megaloblastic anemia, pernicious anemia (also called Addison’s anemia) is characterized by decreased gastric production of hydrochloric acid and deficiency of intrinsic factor (IF), a substance normally secreted by the parietal cells of the gastric mucosa that’s essential for vitamin B₁₂ absorption. The resulting vitamin B₁₂ deficiency causes serious neurologic, gastric, and intestinal abnormalities. Untreated pernicious anemia may lead to permanent neurologic disability and death.

Pernicious anemia primarily affects people of northern European ancestry; in the United States, it’s most common in New England and the Great Lakes region because that is where people of that ancestry are concentrated. It’s rare in children, Blacks, and Asians. Onset typically occurs between ages 50 and 60; incidence rises with increasing age.

Causes

Familial incidence of pernicious anemia suggests a genetic predisposition. A significantly higher incidence in patients with immunologically related diseases — such as thyroiditis, myxedema, and Graves’ disease — seems to support a widely held theory that an inherited autoimmune response causes gastric mucosal atrophy and, therefore, deficiency of hydrochloric acid and IF.

Deficiency of IF impairs absorption of vitamin B₁₂. The resultant vitamin B₁₂ deficiency inhibits cell growth, particularly of red blood cells (RBCs), leading to insufficient and deformed RBCs with poor oxygen-carrying capacity. Vitamin B₁₂ deficiency also impairs myelin formation, causing neurologic damage. Iatrogenic induction of IF deficiency can follow partial gastrectomy.

Signs and symptoms

Characteristically, pernicious anemia has an insidious onset but eventually causes an unmistakable triad of symptoms: weakness, sore tongue, and numbness and tingling in the extremities. The lips, gums, and tongue appear markedly bloodless. Hemolysis-induced hyperbilirubinemia may cause faintly jaundiced sclera and pale to bright yellow skin. The patient may also become highly susceptible to infection, especially of the genitourinary tract.

GI signs and symptoms

Gastric mucosal atrophy and decreased hydrochloric acid production disturb digestion and lead to nausea, vomiting, anorexia, weight loss, flatulence, diarrhea, and constipation. Gingival bleeding and tongue inflammation may hinder eating and intensify anorexia.

Central nervous system signs and symptoms

Nerve demyelination caused by vitamin B₁₂ deficiency initially affects the peripheral nerves but gradually extends to the spinal cord. Consequently, the neurologic effects of pernicious anemia include neuritis, weakness in the extremities, peripheral numbness and paresthesia, disturbed position sense, lack of coordination, ataxia, impaired fine finger movement, positive Babinski’s and Romberg’s signs, light-headedness, optic muscle atrophy, loss of bowel and bladder control, impotence (in males), and altered vision (diplopia, blurred vision), taste, and hearing (tinnitus).

The effects of pernicious anemia on the nervous system may also produce irritability, poor memory, headache, depression, and delirium. Although some of these symptoms are temporary, irreversible central nervous system changes may have occurred before treatment is initiated.

Cardiovascular signs and symptoms

Increasingly fragile cell membranes induce widespread destruction of RBCs, resulting in low hemoglobin (Hb) levels. The impaired oxygen-carrying capacity of the blood secondary to lowered Hb leads to weakness, fatigue, and light-headedness. Compensatory increased cardiac output results in palpitations, wide pulse pressure, dyspnea, orthopnea, tachycardia, premature beats and, eventually, heart failure.

Diagnosis

A positive family history, typical ethnic heritage, and results of blood studies, bone marrow aspiration, gastric analysis, and the Schilling test help establish the diagnosis of pernicious anemia. Laboratory screening must rule out other anemias with similar symptoms, such as folic acid deficiency anemia, because treatment differs.

Diagnosis must also rule out vitamin B₁₂ deficiency resulting from malabsorption due to a GI disorder, gastric surgery, radiation, or drug therapy.

Blood study results that suggest pernicious anemia include:

❑ decreased Hb level (4 to 5 g/dl) and decreased RBC count

❑ increased mean corpuscular volume (greater than 120/µl), because each larger-than-normal RBC contains increased amounts of Hb; mean corpuscular Hb concentration is also increased

❑ low white blood cell and platelet counts and large, malformed platelets

❑ serum vitamin B₁₂–assay levels, less than 0.1 mcg/ml

❑ elevated serum lactate dehydrogenase levels.

Bone marrow aspiration reveals erythroid hyperplasia (crowded red bone marrow), with increased numbers of megaloblasts but few normally developing RBCs. Gastric analysis shows the absence of free hydrochloric acid after histamine or pentagastrin injection.

Schilling test

With the Schilling test, the definitive test for pernicious anemia, the patient receives a small oral dose (0.5 to 2 mcg) of radioactive vitamin B₁₂ after fasting for 12 hours. A larger dose (1 mg) of nonradioactive vitamin B₁₂ is given I.M. 2 hours later, as a parenteral flush, and the radioactivity of a 24-hour urine specimen is measured.

Usually, about 7% of the radioactive vitamin B₁₂ dose is excreted in the first 24 hours; persons with pernicious anemia excrete less than 3%. (With pernicious anemia, the vitamin remains unabsorbed and is passed in the stool.) When the Schilling test is repeated with IF added, the test shows normal excretion of vitamin B₁₂.

Serologic tests

Important serologic findings may include IF antibodies and antiparietal cell antibodies.

Treatment

Early parenteral vitamin B₁₂ replacement can reverse pernicious anemia, minimize complications, and possibly prevent permanent neurologic damage.

Vitamin B₁₂ replacement

An initial high dose of parenteral vitamin B₁₂ causes rapid RBC regeneration. Within 2 weeks, the Hb level should rise to normal, and the patient’s condition should markedly improve. Because rapid cell regeneration increases the patient’s iron and folate requirements, concomitant iron and folic acid replacement is necessary to prevent iron deficiency anemia.

After the patient’s condition improves, the vitamin B₁₂ dosage can be decreased to maintenance levels and given monthly. Because such injections must be continued for life, patients should learn how to do the injections themselves.

Other measures

If anemia causes extreme fatigue, the patient may require bed rest until his Hb level rises. If his Hb level is dangerously low, blood transfusions, digoxin, a diuretic, and a low-sodium diet for heart failure may be needed. Most important is the replacement of vitamin B₁₂ to control the condition that led to this failure. Antibiotics help combat accompanying infections.

Special considerations

❑ Supportive measures minimize the risk of complications and speed recovery. Patient and family teaching can promote compliance with lifelong vitamin B₁₂ replacement.

❑ If the patient has severe anemia, plan activities, rest periods, and necessary diagnostic tests to conserve energy. Monitor pulse rate often; tachycardia means activities are too strenuous.

❑ Warn the patient to guard against infections, and tell him to report signs of infection promptly, especially respiratory and urinary tract infections, because the patient’s weakened condition may increase susceptibility.

❑ Provide a well-balanced diet, including foods high in vitamin B₁₂ (meat, liver, fish, eggs, and milk). Offer between-meal snacks, and encourage the family to bring favorite foods from home.

❑ Because a sore mouth and tongue make eating painful, ask the dietitian to avoid giving the patient irritating foods. If these symptoms make talking difficult, supply a pad and pencil or some other aid to facilitate nonverbal communication; explain this problem to the family. Provide diluted mouthwash or, with severe conditions, swab the patient’s mouth with tap water or warm saline solution.

❑ Warn the patient with a sensory deficit not to use a heating pad because it may cause burns.

❑ If the patient is incontinent, establish a regular bowel and bladder routine. After the patient is discharged, a visiting nurse should follow up on this schedule and make adjustments as needed.

❑ If neurologic damage causes behavioral problems, assess mental and neurologic status often; if necessary, give tranquilizers as ordered, and apply a jacket restraint at night.

❑ Stress to the patient that vitamin B₁₂ replacement isn’t a permanent cure and that these injections must be continued for life, even after symptoms subside.

CLINICAL TIP: To prevent pernicious anemia, emphasize the importance of vitamin B₁₂ supplements for patients who have had extensive gastric resections or those who follow strict vegetarian diets.

Book Source Details

• Book Title: Handbook of Diseases
• Author(s): Springhouse
• Year of Publication: 2003
• Copyright Details: Handbook of Diseases, Copyright © 2003 Lippincott Williams & Wilkins.

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