Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published February 13, 2019


How is pernicious anemia treated?

Vitamin B12 deficiency can cause a range of neuropsychiatric symptoms, including psychosis, personality changes, and affective symptoms, in addition to cognitive impairment. It commonly causes paresthesia. Vitamin B12 deficiency typically causes macrocytic anemia. Read the latest Case Records of the Massachusetts General Hospital here

Clinical Pearls

Q: What laboratory abnormalities are seen in isolated vitamin B12 deficiency versus isolated folate deficiency?

A: Vitamin B12 and folate are required for metabolism of homocysteine to methionine, whereas vitamin B12 but not folate is required for metabolism of methylmalonyl–coenzyme A (methylmalonic acid linked to coenzyme A) to succinyl–coenzyme A. Thus, isolated folate deficiency can produce an elevation in the homocysteine level but not in the methylmalonic acid level. In contrast, isolated vitamin B12 deficiency can produce an elevation in both the methylmalonic acid level and the homocysteine level.

Q: What is the most common cause of severe vitamin B12 deficiency?

A: Severe vitamin B12 deficiency is most commonly caused by autoimmune gastritis. It can also arise from other malabsorptive conditions (e.g., inflammatory bowel disease, atrophic gastritis, or pancreatic insufficiency), develop after certain procedures (e.g., bariatric surgery or ileal resection), occur with the use of restricted diets (e.g., veganism) or certain medications (e.g., proton-pump inhibitors or metformin), or arise from hypermetabolic states (including pregnancy) or inborn errors of metabolism.

Morning Report Questions

Q: Is the presence of intrinsic-factor antibodies sensitive and specific for pernicious anemia?

A: The presence of intrinsic-factor antibodies is highly specific but somewhat insensitive for pernicious anemia. In contrast, the presence of parietal-cell antibodies is highly sensitive but nonspecific for this diagnosis. Patients with pernicious anemia sometimes have elevated indirect bilirubin and lactate dehydrogenase levels due to hemolysis.

Q: How is pernicious anemia treated?

A: Treatment of pernicious anemia consists of a repletion phase with weekly parenteral doses of vitamin B12 (cyanocobalamin or hydroxocobalamin), followed by a maintenance phase with monthly intramuscular doses that are continued indefinitely. Parenteral administration bypasses the impairment of oral absorption that is a hallmark of pernicious anemia. For patients with acute neuropsychiatric impairment, an intensive regimen (intramuscular doses of 1000 μg every 24 to 48 hours until symptoms resolve or plateau) has been suggested. The biochemical effect of repletion on methylmalonic acid and homocysteine levels and on hematopoietic effects (i.e., a rise in the reticulocyte count) should be evident within 5 to 10 days.

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