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Low levels of vitamin B12 are seen in folate deficiency, HIV, and multiple myeloma.
Elevated levels of vitamin B12 are seen in renal disease, occult malignancy, and alcoholic liver disease and as a result of technical error.
Macrocytosis may be due to folate deficiency, reticulocytosis, medications, bone marrow dysplasia, and hypothyroidism or be masked by concomitant microcytic anemia.
Serum homocysteine and MMA
Elevated in B12 deficiency secondary to decreased metabolism
If both are normal, B12 deficiency is effectively ruled out.
If MMA is normal and homocysteine is increased, think folate deficiency.
PA
Check antibody to intrinsic factor; positive test is confirmatory for PA, but sensitivity is only 50 " “70%.
Anti-parietal cell antibody positivity indicates PA.
For patients who are antibody positive, consider screening for autoimmune thyroid disease.
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Pregnancy Considerations
Because B12 crosses the placenta, pregnant women with low levels of B12 are at higher risk of having children with neural tube defects, congenital heart defects, developmental delay, and failure to thrive.
Exclusively breastfed infants of mothers who are B12 deficient are at risk of developing B12 deficiency. Infants breastfed from B12-deficient mothers might not show signs or symptoms until 4 to 6 months of age, which may include developmental regression, feeding difficulties, lethargy, or hypotonia.
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Diagnostic Procedures/Other
- Bone marrow exam is usually unnecessary in the evaluation of B12 deficiency because of the inability to differentiate from folate deficiency.
- Spinal cord imaging is not standard; MRI in selected cases, especially with severe myelopathy
TREATMENT
MEDICATION
- Parenteral cyanocobalamin replacement recommended in patients with severe neurologic symptoms: IM cyanocobalamin (2)[C]
- 1,000 Ž ¼g/day for 7 days, then
- 1,000 Ž ¼g weekly for 4 weeks, then
- 1,000 Ž ¼g monthly for life
- High-dose, daily oral cyanocobalamin at doses of 1,000 to 2,000 Ž ¼g are as effective as monthly intramuscular injection and is the preferred route of initial therapy in most circumstances because it is cost-effective and convenient (3)[A]. Requires greater patient compliance. Transnasal and buccal preparations of cyanocobalamin are also available; however, further study is needed.
ALERT
Folic acid without vitamin B12 in patients with PA is contraindicated; it will not correct neurologic abnormalities.
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INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Consider blood transfusion for severe anemia.
- Draw blood for hematologic parameters before transfusing.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Hematologic
- Reticulocytosis in 1 week
- Rise in hemoglobin beginning at 10 days; usually will return to normal in 6 to 8 weeks
- Monitor potassium in profoundly anemic patients (hypokalemia due to potassium use).
- Serum MMA decreases with replacement therapy.
- Neurologic: can note improvement within 3 months of treatment; however, maximum improvement noticed at 6 to 12 months. Some symptoms may be irreversible.
DIET
Meat, animal protein, and legumes unless contraindicated ‚
REFERENCES
11 Lachner ‚ C, Steinle ‚ NI, Regenold ‚ WT. The neuropsychiatry of vitamin B12 deficiency in elderly patients. J Neuropsychiatry Clin Neurosci. 2012;24(1):5 " “15.22 Stabler ‚ SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149 " “160.33 Vidal-Alaball ‚ J, Butler ‚ CC, Cannings-John ‚ R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2005;(3):CD004655.
ADDITIONAL READING
- Allen ‚ LH. How common is vitamin B-12 deficiency? Am J Clin Nutr. 2009;89(2):693S " “696S.
- Bizzaro ‚ N, Antico ‚ A. Diagnosis and classification of pernicious anemia. Autoimmun Rev. 2014;13(4 " “5):565 " “568.
- Fern ƒ ¡ndez-Ba ƒ ±ares ‚ F, Monz ƒ ³n ‚ H, Forne ‚ M. A short review of malabsorption and anemia. World J Gastroenterol. 2009;15(37):4644 " “4652.
- Langan ‚ RC, Zawistoski ‚ KJ. Update on vitamin B12 deficiency. Am Fam Physician. 2011;83(12):1425 " “1430.
- Mazokopakis ‚ EE, Starakis ‚ IK. Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency. Diabetes Res Clin Pract. 2012;97(3):359 " “367.
- Oberley ‚ MJ, Yang ‚ DT. Laboratory testing for cobalamin deficiency in megaloblastic anemia. Am J Hematol. 2013;88(6):522 " “526.
CODES
ICD10
- E53.8 Deficiency of other specified B group vitamins
- D51.0 Vitamin B12 defic anemia due to intrinsic factor deficiency
- D51.3 Other dietary vitamin B12 deficiency anemia
- D51.1 Vitamin B12 deficiency anemia due to selective vitamin B12 malabsorption with proteinuria
- D51.9 Vitamin B12 deficiency anemia, unspecified
- D51.8 Other vitamin B12 deficiency anemias
- D51.9 Vitamin B12 deficiency anemia, unspecified
ICD9
- 266.2 Other B-complex deficiencies
- 266.2 Other B-complex deficiencies
- 281.0 Pernicious anemia
- 281.1 Other vitamin B12 deficiency anemia
- 281.1 Other vitamin B12 deficiency anemia
SNOMED
- 64117007 Vitamin B12 deficiency (non anemic) (disorder)
- 64117007 Vitamin B12 deficiency (non anemic) (disorder)
- 84027009 Pernicious anemia (disorder)
- 190634004 Cobalamin deficiency (disorder)
CLINICAL PEARLS
- Consider screening for B12 deficiency in high-risk patients including the elderly and monitoring B12 levels annually if on metformin or on chronic PPIs.
- Correcting folate deficiency without treating with cyanocobalamin in megaloblastic anemia may correct hematologic but not neurologic disorders.
- Vitamin B12 deficiency can coexist with other causes of anemia, including iron deficiency or hemolysis; thus, MCV can be normal, decreased, or increased.
- For patients with PA, cyanocobalamin replacement must be lifelong.
- Patients with PA are at increased risk for other autoimmune conditions as well as gastric malignancy.