Evidence map›Paper›PMID 41498143›Full record

ArticleInternational journal of laboratory hematology2026

Unexplained Elevated Vitamin B12: Consider Macro-B12.

Evelien G E Hurkmans, Ruben Deneer, Marten R Nijziel, Volkher Scharnhorst

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Article in International journal of laboratory hematology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

4 authors.

Evelien G E HurkmansClinical Laboratory, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.ORCID https://orcid.org/0000-0002-1333-1496
Ruben DeneerClinical Laboratory, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.
Marten R NijzielCatharina Cancer Institute, Department of Internal Medicine/Hematology, Catharina Hospital, Eindhoven, the Netherlands.
Volkher ScharnhorstClinical Laboratory, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionElevated vitamin B12 concentration can be caused by supplementation, liver disease, kidney disease, or myeloid malignancies. Persistent, unexplained elevations of vitamin B12 can raise concern among patients and may lead to invasive diagnostic procedures, including bone marrow biopsy. A potential benign cause of this elevation is macro-B12, a complex of vitamin B12, transcobalamin, and immunoglobulins. Although not bioactive, this complex can cause elevated plasma vitamin B12 concentrations due to reduced clearance.

methodsPolyethylene glycol (PEG) precipitation is a laboratory technique that can be used to support the suspicion of macro-B12. Here, a case is described in which a PEG precipitation could potentially have prevented an unnecessary bone marrow biopsy. In addition, the presence of macro-B12 was studied in a group of patients with and without myeloid malignancies.

resultsMacro-B12 was identified in 24% of 72 individuals with vitamin B12 > 1476 pmol/L. In one of these patients, a functional vitamin B12 deficiency was confirmed by an elevated methylmalonic acid (MMA) concentration. Macro-B12 was not detected in 8 patients with a myeloid malignancy.

conclusionThese findings suggest that, in patients with persistently elevated vitamin B12 concentrations and a low suspicion of a myeloid malignancy, PEG precipitation may help to explain the elevated vitamin B12 and prevent unnecessary diagnostic procedures including bone marrow punctures.

Indexed as

Vitamin B 12AgedFemaleHumansMaleMiddle AgedPolyethylene GlycolsTranscobalaminsVitamin B 12 DeficiencyPolyethylene GlycolsTranscobalaminsVitamin B 12immune complexesimmunoassaymacro‐B12myeloid leukemiapolyethylene glycolsvitamin B12

Identifiers

PMID41498143
PMCPMC13155288

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