Management of Mild Macrocytosis in a Healthy Young Adult
For a previously healthy 19-year-old female with an isolated MCV of 99 fL (just 2 fL above the upper limit of normal) and otherwise completely normal CBC and CMP, no immediate intervention is required, but a focused evaluation should be performed to exclude common reversible causes. 1
Initial Diagnostic Workup
This degree of macrocytosis (MCV 99 fL) is borderline and may not represent true pathology, but warrants a systematic evaluation:
First-Line Laboratory Tests
Reticulocyte count is the critical first test to distinguish between production defects versus increased red cell turnover (hemolysis or recent hemorrhage). 1, 2
Vitamin B12 level should be checked, as deficiency can occur even in young patients and may present with isolated macrocytosis before anemia develops. 2
Serum and RBC folate levels should be measured, particularly given the patient's age and potential dietary patterns. 2
- Deficiency indicated by serum folate <10 nmol/L (4.4 μg/L) or RBC folate <305 nmol/L 2
TSH should be checked to exclude hypothyroidism, which commonly causes macrocytosis. 2, 3
Additional Considerations
Medication review is essential, as drugs like methotrexate, azathioprine, hydroxyurea, and anticonvulsants cause macrocytosis. 1, 3
Alcohol use history should be obtained, as alcohol is one of the most common causes of non-megaloblastic macrocytosis. 3, 4
Red cell distribution width (RDW) from the existing CBC should be evaluated—an elevated RDW suggests coexisting iron deficiency that may be masked by macrocytosis. 1, 2
Mean corpuscular hemoglobin (MCH) is more sensitive than MCV for detecting iron deficiency and should be reviewed from the existing CBC. 1
- A reduced MCH despite macrocytosis indicates a mixed picture requiring iron studies 1
Management Based on Findings
If All Tests Are Normal
Monitor with repeat CBC in 3-6 months to ensure MCV stability, as this mild elevation may represent normal variation for this patient. 1
Reassess B12 and folate periodically, as deficiencies can develop over time even with initially normal levels. 1
If Vitamin Deficiency Is Identified
Never initiate folate supplementation before excluding B12 deficiency, as folate can mask B12 depletion and precipitate subacute combined degeneration of the spinal cord. 2, 3
For confirmed B12 deficiency: 1 mg intramuscularly three times weekly for 2 weeks, then 1 mg every 2-3 months. 2
For folate deficiency (after excluding B12 deficiency): oral folic acid 5 mg daily for minimum 4 months. 2
When to Consider Hematology Referral
Hematology consultation is recommended if the cause remains unclear after initial workup, if MCV progressively worsens, or if other cytopenias develop. 1, 2
The presence of other cytopenias significantly increases concern for bone marrow disorders and warrants more aggressive evaluation. 1
Critical Pitfalls to Avoid
Do not dismiss mild macrocytosis without evaluation, as 9-21% of patients with B12 deficiency present with isolated macrocytosis without anemia. 5
Do not assume normal ferritin excludes iron deficiency in the presence of inflammation—ferritin up to 100 μg/L may still indicate iron deficiency when inflammation is present. 1, 3
Do not overlook medication-induced macrocytosis, particularly with thiopurines, which cause myelosuppression rather than vitamin deficiency. 1, 3
Do not neglect follow-up, as a significant percentage of patients with unexplained macrocytosis may develop primary bone marrow disorders over time. 1