Pernicious Anemia Treatment & Management

Updated: May 16, 2022
  • Author: Srikanth Nagalla, MD, MS, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Approach Considerations

The following goals are the most important in establishing care for patients with pernicious anemia:

  • To establish that the patient has cobalamin deficiency

  • If there is evidence for folic acid deficiency but pernicious anemia has not been ruled out, treat with both folic acid and cobalamin until pernicious anemia has been ruled out. The reason is that folic acid restores blood counts but does not prevent the development of subacute combined system degeneration in patients with pernicious anemia.

  • To determine the cause of the failure to absorb cobalamin (This goal is somewhat controversial. Not all hematologists work to establish the precise cause of low vitamin B12 levels. The nuclear medicine tests are expensive and cumbersome, and as a result, many hematologists simply proceed to treatment once a differential diagnosis of a low vitamin B12 state is established.)

  • To treat the patient with adequate doses of cobalamin

  • To confirm the diagnosis by documenting that specific therapy is effective

  • To ensure administration of adequate quantities of cobalamin for the lifespan of the patient

Once therapy is started, hospitalization is necessary only for patients with severe life-threatening anemia. It may be required until patients develop an adequate hematologic response.

Patients whose cobalamin deficiency is due to underlying diseases involving the intestine or pancreas may require additional therapy. Examples of additional therapy are surgical correction of anatomic abnormalities of the gut that produce small bowel bacterial overgrowth, or the treatment of fish tapeworm anemia or pancreatitis. Elderly patients who also have hypokalemia should receive oral potassium supplements, to prevent severe hypokalemia and possible arrhythmias.

Go to Anemia, Iron Deficiency Anemia, and Chronic Anemia for complete information on these topics.


Cobalamin Therapy

Vitamin B12 is available for therapeutic use parenterally as either cyanocobalamin or hydroxocobalamin. [26] The two forms are equally useful in the treatment of vitamin B12 deficiency, and both are nontoxic (except for rare allergic reactions). Theoretical advantages exist to using hydroxocobalamin because it is retained better in the body and is more available to cells; however, both chemical forms of cobalamin provide prompt correction.

Cobalamin is available in a solution for injection in doses ranging from 100 to 1000 µg. Most of the injected doses in excess of 50 µg are rapidly excreted in the urine. Thus, when therapy is started, repeated doses are recommended in order to replenish body stores.

A number of regimens have been recommended. One regimen begins with daily subcutaneous administration for the first week. If significant reticulocytosis confirms that therapy is successful, doses are then administered twice weekly for another 4-5 weeks. After this period, 100 µg can be administered monthly by subcutaneous or intramuscular injection. Lifetime compliance is necessary. An alternative regimen involves weekly injections of 1000 µg of vitamin B12 for 5-6 weeks, followed by monthly injections.

Cobalamin deficiency–related neurological impairment can vary in clinical presentation, including acute combined system degeneration, peripheral neuropathy, and psychosis. These neuropathies should be treated more aggressively.

Response should be monitored by reticulocyte counts, lactic dehydrogenase (LDH), and an appropriate rise in hemoglobin levels. LDH levels decrease and hemoglobin levels increase by about 1 g/dL/wk. A rise in LDH might indicate a relapse.

Limited studies have shown that adequate therapy can be maintained after the initial parenteral loading doses through oral ingestion of 250-1000 µg of vitamin B12 daily. Even with a total absence of intrinsic factor (IF), about 1% of an oral dose is absorbed, and the daily requirement for vitamin B12 is 1 µg/d. A study by Zhang and colleagues found evidence that using orally ingested soy protein isolate (SPI) nanoparticles as a carrier can improve the intestinal transport and absorption of vitamin B12. [27]

The oral route may be necessary in the rare patients who have allergic reactions to parenteral administration, or in patients receiving anticoagulant or antiplatelet agent therapy, in whom intramuscular injections are contraindicated. [28] If this route is used, obtain serum cobalamin measurements at periodic intervals to ensure that adequate quantities of cobalamin have been absorbed. Oral cobalamin therapy should not be used in patients with neurologic symptoms.

A randomized, placebo-controlled trial of oral cobalamin therapy in 50 patients with borderline serum vitamin B12 levels (125-200 pg/mL) and nonspecific symptoms compatible with subtle vitamin B12 deficiency found that after 1 month, serum methylmalonic acid (MMA) levels were corrected more often in patients receiving oral cobalamin than in those receiving placebo. However, the benefit to the MMA level disappeared after 3 additional months without cobalamin therapy. [29]

A study found that oral cobalamine was more effective than parenteral therapy in some circumstances. [29]


Blood Transfusions

Transfusions are rarely required in patients with a megaloblastic anemia that is due to vitamin B12 deficiency. The likelihood of obtaining a dramatic response to cobalamin therapy within a few days of initiating treatment makes it unnecessary to subject the patient to the hazards of blood transfusion.

Usually, mild-to-moderate congestive heart failure secondary to anemia abates with bed rest and low-dosage diuretic therapy. However, if the congestive heart failure is severe or the patient has coronary insufficiency, transfusion of packed red blood cells may be necessary.

Transfuse the blood slowly because patients who are transfused for severe anemia often develop circulatory overload. For this reason, low-dose diuretic therapy is often employed with transfusion.


Dietary Measures and Activity Restriction

People who are strict vegetarians and, most particularly, people who do not consume eggs, milk, or meat can develop cobalamin deficiency. Counsel these people to either change their dietary habits or remain on supplementary vitamin B-12 therapy for their lifetime. An oral tablet of 100-200 µg taken weekly should provide adequate therapy.

Patients with severe anemia should curtail strenuous physical activity until they develop an adequate hematologic response after treatment.



Because an increased familial incidence of pernicious anemia exists, family members should be aware that they are at greater risk of developing this disease and should seek medical attention promptly if they develop anemia or mental and neurologic symptoms. Monitor siblings and children of patients with a hereditary abnormality of cobalamin deficiency for evidence of the specific defect in cobalamin transport or metabolism.

Determine whether cobalamin deficiency is the etiology in patients who recently developed evidence of mental deterioration.

Prophylactically treat patients with cobalamin when they have undergone total gastrectomy, bypass procedures for weight reduction, ileectomy, pancreatectomy, or when they have atrophic gastritis or chronic inflammatory disease of the ileum.

Strict vegetarians should continue supplementary cobalamin, particularly during pregnancy and while nursing a newborn infant.

Elderly people are at risk for developing pernicious anemia due to achlorhydria. Therefore, serum vitamin B-12 levels should be checked. If low or if cobalamin deficiency is suspected, they should be treated with vitamin B-12 supplementation.


Consultations and Long-Term Monitoring

A consultation with a neurologist may be desirable in patients with unusual neurologic manifestations. Such consultation is most useful in patients without a macrocytic megaloblastic anemia.

Outpatient follow-up of patients with pernicious anemia is required to ensure that they have responded to therapy with cobalamin and that they continue to receive cobalamin on a regular basis for the remainder of their lives. Most patients can be taught to self-administer cobalamin subcutaneously so that they can minimize their visits to the physician.