What initial investigations should I perform for a patient with macrocytosis and no obvious symptoms?

Guideline-aligned answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MRCGP.

Posted: 22 August 2025 Guideline-Aligned (High Confidence) Clinically Reviewed
Dr Kola Tytler MBBS CertHE MBA MRCGPClinical Lead • iatroX

For a patient presenting with macrocytosis without obvious symptoms, the initial investigation should include testing for vitamin B12 deficiency using either total serum B12 (serum cobalamin) or active B12 (serum holotranscobalamin) as the first-line diagnostic test.

Before starting vitamin B12 replacement, blood samples for these diagnostic tests should be taken.

If the initial B12 test result is indeterminate, consider further testing with serum methylmalonic acid (MMA) concentrations to clarify the diagnosis.

Additionally, consider other causes of macrocytosis if vitamin B12 deficiency is unlikely based on test results.

Educational content only. Always verify information and use clinical judgement.