Vitamin B<sub>12</sub>
Vitamin B12
    
Number
001503
CPT
82607
Related Information
  • Anemia Profile, Megaloblastic, Serum
  • Folate (Folic Acid)
  • Synonyms
    B12 ; Cobalamin, True
    Specimen
    Serum
    Volume
    1 mL
    Minimum Volume
    0.3 mL (Note: This volume does not allow for repeat testing.)
    Container
    Red-top tube or gel-barrier tube
    Collection
    If a red-top tube is used, transfer separated serum to a plastic transport tube.
    Storage Instructions
    Refrigerate
    Patient Preparation
    Fasting specimen preferred; must draw before Schilling test, transfusions or B12 therapy is started.
    Causes for Rejection
    Plasma specimen
    Reference Interval
    211-911 pg/mL
    Use
    Detect B12 deficiency as in pernicious anemia; diagnose folic acid deficiency; evaluate hypersegmentation of granulocyte nuclei; follow up MCV >100; diagnose macrocytic anemia; diagnose megaloblastic anemia; evaluate alcoholism, prenatal care; evaluate malabsorption, neurological disorders, or the elevation of B12 as seen in liver cell damage or myeloid leukemia
    Limitations
    Drugs capable of interference with absorption of B12 and/or folic acid include chemotherapeutic agents (methotrexate), antimalarial (pyrimethamine), diuretics (triamterene), protozoacides (pentamidine, isethionate), antibacterials (trimethoprim), anticonvulsants (phenytoin), sedatives (barbiturates), oral contraceptives, antituberculosis agents (cycloserine, para-aminosalicylic acid), antigout (colchicine), oral hypoglycemic, biguanide group (metformin, phenformin). Establishing functional cobalamin (B12) sufficiency in any individual patient may require consideration of intra-individual variation, functional status of the gastric mucosa (in particular in elderly individuals) and transcobalamin II binding.1,2
    Methodology
    Immunochemiluminometric assay (ICMA)
    Additional Information
    Conditions associated with decreased vitamin B12 include hypochlorhydria; pernicious anemia (PA) in which cobalamin levels may vary from 0 to overlapping lower limits of patients without PA; disorders of intestinal absorption, or inflammatory bowel disease; prior gastric surgery; intestinal surgery (diminished B12 or folate or both are found in 88% of patients with jejunoileal bypass operated for morbid obesity);3 resection of terminal ileum as for Crohn disease prevents absorption of B12; oral contraceptives; abnormalities of cobalamin transport or metabolism.2 A significant rise in MCV may be an important early indicator of B12 deficiency.4 Conditions associated with increased vitamin B12 include chronic granulocytic leukemia (and to a lesser degree leukemoid states); chronic renal failure; severe congestive heart failure; diabetes; obesity; COPD and cases of liver cell damage.

    There is growing evidence that elevated serum or urine methylmalonic acid (MMA) levels may be a more definitive indication of early cobalamin (B12) deficiency. MMA serum level, when increased, reflects decreased tissue cobalamin and is an early indicator of B12 deficiency. Cobalamin dependent neurologic disease with normal hematologic parameters and serum B12 levels may be associated with significant elevations of serum methylmalonic acid.5,6 GC/MS methodology for MMA determinations is preferred. To avoid dietary influence serum MMA levels have preference over urine studies in nonfasting patients.7

    Footnotes
    1. Lindstedt G, Lundberg PA, Johansson PM, et al, “High Prevalence of Atrophic Gastritis in the Elderly: Implications for Health-Associated Reference Limits for Cobalamin in Serum,” Clin Chem, 1989, 35(7):1557-9.
    2. Herzlich B and Herbert V, “Depletion of Serum Holotranscobalamin II. An Early Sign of Negative Vitamin B12 Balance,” Lab Invest, 1988, 58(3):332-7.
    3. Hocking MP, Duerson MC, O'Leary JP, et al, “Jejunoileal Bypass for Morbid Obesity. Late Follow-up in 100 Cases,” N Engl J Med, 1983, 308(17):995-9.
    4. Hall CA, “Vitamin B12 Deficiency and Early Rise in Mean Corpuscular Volume,” JAMA, 1981, 245(11):1144-6.
    5. Lindenbaum J, Healton EB, Savage DG, et al, “Neuropsychiatric Disorders Caused by Cobalamin Deficiency in the Absence of Anemia or Macrocytosis,” N Engl J Med, 1988, 318(26):1720-8.
    6. Rasmussen K, Moelby L, and Jensen MK, “Studies on Methylmalonic Acid in Humans. II. Relationship Between Concentrations in Serum and Urinary Excretion, and the Correlation Between Serum Cobalamin and Accumulation of Methylmalonic Acid,” Clin Chem, 1989, 35(12):2277-80.
    7. Rasmussen K, “Studies on Methylmalonic Acid in Humans. I. Concentrations in Serum and Urinary Excretion in Normal Subjects After Feeding and During Fasting and After Loading With Protein, Fat, Sugar, Isoleucine, and Valine,” Clin Chem, 1989, 38(12):2271-6
    References

    Carethers M, “Diagnosing Vitamin B12 Deficiency, A Common Geriatric Disorder,” Geriatrics, 1988, 43(3):89-94, 105-7, 111-2 (review).

    Chanarin I, “Megaloblastic Anaemia, Cobalamin, and Folate,” J Clin Pathol, 1987, 40(9):978-84 (review).

    Gimsing P and Nexo E, “Cobalamin-Binding Capacity of Haptocorrin and Transcobalamin: Age-Correlated Reference Intervals and Values From Patients,” Clin Chem, 1989, 35(7):1447-51.

    Herbert V, “Don't Ignore Low Serum Cobalamin (Vitamin B12) Levels,” Arch Intern Med, 1988, 148(8):1705-7.

    Herbert V, “The 1986 Herman Award Lecture. Nutrition Science as a Continually Unfolding Story: The Folate and Vitamin B12 Paradigm,” Am J Clin Nutr, 1987, 46(3):387-402 (review).

    Steiner I, Kidron D, Soffer D, et al, “Sensory Peripheral Neuropathy of Vitamin B12 Deficiency: A Primary Demyelinating Disease?” J Neurol, 1988, 235(3):163-4.

    Thompson WG, Babitz L, Cassino C, et al, “Evaluation of Current Criteria Used to Measure Vitamin B12 Levels,” Am J Med, 1987, 82(2):291-4.


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