Required section · Section 3 of 6
Use markers and look-alikes with limits
Vitamin B12 and folate deficiency impair DNA synthesis. A serum B12 result alone has method and biologic limitations, so one borderline value cannot establish deficiency. Methylmalonic acid (MMA) and homocysteine can provide functional evidence in the appropriate context. The cited MMA decision point is 0.40 micromol/L; use the local assay interval rather than a second universal cutoff. Renal insufficiency can elevate MMA and reduce its specificity, and homocysteine has non-B12 causes.
Use a medication pattern-and-action comparison rather than a long drug list. Do not attribute macrocytosis to a drug without medication history and qualified review; alcohol, liver disease, hypothyroidism, pregnancy, and marrow disorders remain nonmedication differentials.
| Pattern or context | Examples | Laboratory action |
|---|---|---|
| Folate-pathway interference | Methotrexate; trimethoprim | Correlate medication history and folate-pathway context. |
| Macrocytosis-associated exposure | Hydroxyurea; antiretrovirals; anticonvulsants; chemotherapy | Document exposure and correlate the CBC and smear; use qualified review if cytopenias or dysplasia are present. |
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