Diagnostic Approach to Elevated MCV and RDW
The most likely diagnosis is vitamin B12 or folate deficiency causing megaloblastic macrocytic anemia, and you must check serum vitamin B12, folate levels, and reticulocyte count immediately to guide treatment. 1, 2
Initial Laboratory Workup
The minimum diagnostic workup must include: 1, 2
- Complete blood count with MCV and RDW - The elevated RDW is particularly important as it can indicate coexisting iron deficiency even when macrocytosis is present 1
- Reticulocyte count - This is critical to differentiate megaloblastic from non-megaloblastic causes. A low or normal reticulocyte count points toward vitamin deficiencies, medications, or myelodysplastic syndrome, while an elevated count suggests hemolysis or recent hemorrhage 1, 2
- Serum vitamin B12 level - Deficiency is defined as <150 pmol/L or <203 ng/L 2
- Serum folate and RBC folate - Deficiency indicated by serum folate <10 nmol/L or RBC folate <305 nmol/L 2
- Serum ferritin and transferrin saturation - Essential because microcytosis and macrocytosis can coexist and neutralize each other, resulting in a falsely normal MCV 1
- CRP - To assess for inflammation which can elevate ferritin and mask iron deficiency 1, 2
Peripheral Smear Findings
Examine the peripheral smear for macro-ovalocytes and hypersegmented neutrophils, which confirm megaloblastic anemia from B12 or folate deficiency. 3, 4 Round macrocytes without these features suggest liver disease or alcohol toxicity rather than vitamin deficiency 5, 3
Treatment Algorithm
Critical Treatment Sequence
Always treat vitamin B12 deficiency BEFORE initiating folate supplementation to prevent precipitating subacute combined degeneration of the spinal cord. 2, 6 This is a non-negotiable principle - folic acid can mask the hematologic manifestations of B12 deficiency while allowing irreversible neurologic damage to progress 1, 6
For Confirmed Vitamin B12 Deficiency:
- Administer 1 mg vitamin B12 intramuscularly three times weekly for 2 weeks, then 1 mg every 2-3 months for life 2
- If neurological symptoms are present, use hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then 1 mg every 2 months 2
For Folate Deficiency (after excluding B12 deficiency):
- Oral folic acid 5 mg daily for minimum 4 months 2
Critical Pitfalls to Avoid
Do not give folic acid alone without first checking B12 levels. Doses of folic acid greater than 0.1 mg daily can produce hematologic remission in B12-deficient patients while neurologic damage progresses irreversibly 6. This represents one of the most dangerous errors in managing macrocytic anemia.
Monitor serum potassium closely during the first 48 hours of treatment in patients with pernicious anemia, as rapid cell production can cause hypokalemia 6
Check for coexisting iron deficiency - The elevated RDW in your patient suggests this possibility. In inflammatory conditions, ferritin up to 100 μg/L may still indicate iron deficiency 1, 2
Monitoring Response
- Repeat reticulocyte count and hematocrit daily from days 5-7 of therapy 6
- Reticulocytes should increase to at least twice normal while hematocrit remains below 35% 6
- An increase in hemoglobin of at least 2 g/dL within 4 weeks indicates adequate response 2
- If reticulocytes fail to increase appropriately, reassess for complicating conditions including iron deficiency, folate deficiency, or underlying bone marrow disease 6
When to Refer to Hematology
Refer if the cause remains unclear after complete workup, or if you suspect myelodysplastic syndrome - particularly with concurrent leukopenia and/or thrombocytopenia 2, 4 MDS becomes increasingly common in elderly patients and requires bone marrow evaluation 4