How should I interpret high serum vitamin B12 levels in my patient with anemia?

High serum B12 levels, aka hypercobalaminemia (HC),  is not rare among hospitalized patients with 1 study reporting “high” (813-1355 pg/ml) and “very high” (>1355 pg/ml) serum B12 levels in 13 and 7% of patients, respectively1. Common causes include excess B12 intake, solid neoplasms (particularly, hepatocellular carcinoma and metastatic neoplastic liver disease), blood disorders (eg, myelodysplastic syndrome, CML, and acute leukemias, particularly AML3), and other liver diseases, including alcohol-related diseases as well as acute and chronic hepatitis.  Other inflammatory states and renal failure have also been reported2.  

Paradoxically, even in the presence of HC, a functional B12 deficiency may still exist. This may be related to poor B12 delivery to cells due to its high binding by transport proteins transcobalamin I and III in HC which may in turn cause a decrease in the binding of B12 to transcobalamin II, a key player in B12 transport to tissues2.  In this setting, elevated serum methylmalonic acid and homocysteine levels may be helpful.

References:

  1. Arendt JFB, Nexo E. Cobalamin related parameters and disease patterns in patients with increased serum cobalamin levels. PLoS ONE 2012;9:e45979.
  2. Andres E, Serraj K, Zhu J. et al. The pathophysiology of elevated vitamin B12 in clinical practice. Q J Med 2013;106:505-515.
How should I interpret high serum vitamin B12 levels in my patient with anemia?

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