Vitamin B12 deficiency Diagnosis and management Serum vitamin B12 and folate Q Does the patient have suspected vitamin B12 deficiency? No Consider alternative diagnoses. Yes Assess serum vitamin B12 and folate levels in patients with suspected vitamin B12 deficiency. A Diagnostic criteria Q Is serum vitamin B12 < 148 pmol/L? Q Is serum vitamin B12 lower than the local reference range? Yes to any Suspect vitamin B12 or folate deficiency in patients with a blood film showing oval macrocytes and hypersegmented neutrophils in the presence of an elevated MCV. B Diagnose vitamin B12 deficiency based on vitamin B12 levels of < 148 pmol/L (200 ng/L) or if vitamin B12 levels are below the LLN for the local reference range, in the presence of strong clinical suspicion. B Recognize that low serum vitamin B12 levels may be seen in the presence of folate deficiency, or due to technical issues with measurement, and neurological symptoms due to cobalamin deficiency may occur in the presence of a normal MCV. B No to all Serum homocysteine and methylmalonic acid BSH Q Is there a strong clinical suspicion of vitamin B12 deficiency? Yes Obtain further evaluation with MMA, serum total homocysteine, or holotranscobalamin in patients with serum cobalamin levels > 148 pmol/L in the presence of a strong clinical suspicion of cobalamin deficiency, and administer a trial of hydroxocobalamin to ascertain any clinical improvement. B Consider obtaining serum total homocysteine and/or MMA, depending on availability, as supplementary tests to determine biochemical cobalamin deficiency in the presence of clinical suspicion of deficiency but an indeterminate serum cobalamin level. C No Consider alternative diagnoses. Evaluation for pernicious anemia Q Does the patient have anemia? Q Does the patient have neutropathy? Q Does the patient have glossitis? Q Are there other reasons to suspect pernicious anemia? Yes to any Obtain anti-intrinsic factor antibodies in patients with suspected pernicious anemia presenting with anemia, neuropathy, and/or glossitis, regardless of serum vitamin B12 levels. A Obtain anti-intrinsic factor antibodies to identify early/latent presentation of pernicious anemia in patients with a low serum cobalamin level in the absence of anemia and food malabsorption (or other causes of deficiency). B Obtain anti-intrinsic factor antibodies for probable concurrence of pernicious anemia in patients with T2DM and a low serum cobalamin. Do not exclude antibody-negative pernicious anemia if negative. B Do not obtain anti-gastric parietal cell antibodies for the diagnosis of pernicious anemia. D No to all Patients with pernicious anemia Q Does the patient have positive anti-intrinsic factor antibodies? Q Does the patient have vitamin B12 deficiency of unknown etiology? No to all Continue management and follow-up as clinically appropriate Yes to any Initiate lifelong cobalamin replacement in patients with vitamin B12 deficiency and positive anti-intrinsic factor antibodies. A Initiate lifelong cobalamin replacement in patients with vitamin B12 deficiency and negative anti-intrinsic factor antibodies where no other causes of deficiency have been identified, as these patients may have anti-intrinsic factor-negative pernicious anemia. B No to all Continue management and follow-up as clinically appropriate.