Vitamin B12 Deficiency
This patient has vitamin B12 deficiency causing megaloblastic anemia, confirmed by the combination of macrocytosis (MCV 102), low B12 (211), elevated methylmalonic acid (580), and hypersegmented neutrophils on peripheral smear.
Diagnostic Reasoning
The clinical picture definitively points to B12 deficiency:
- Macrocytic anemia (MCV 102) with hypersegmented neutrophils is the hallmark of megaloblastic anemia 1
- Low-normal B12 (211) can still represent true deficiency, as some patients with low-normal serum B12 levels manifest hematologic, neurologic, or psychiatric symptoms 2
- Elevated methylmalonic acid (580) confirms B12 deficiency even when serum B12 is borderline, as MMA is elevated specifically in B12 deficiency 2
- Normal ferritin (220) excludes iron deficiency
- Normal folate (12) excludes folate deficiency
Why Not the Other Options?
- Myelodysplastic syndrome: While MDS can cause macrocytosis 1, the elevated MMA and low B12 make this diagnosis secondary. MDS would be considered only if B12 replacement fails to correct the anemia
- Anemia of chronic disease: Typically normocytic, not macrocytic, and would not explain the elevated MMA 1, 3
- Hemolysis: Would show elevated reticulocyte count, which is absent in megaloblastic anemia (low reticulocyte index indicates decreased RBC production) 1
- Iron deficiency: Excluded by normal ferritin and macrocytic (not microcytic) MCV 1
Treatment Protocol
Immediate treatment with parenteral vitamin B12 is mandatory given the severity of anemia (Hb 10.2) and presence of fatigue 2, 4.
Initial Treatment Phase
- Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 4
- If neurologic symptoms are present or suspected (assess for sensory/motor symptoms, gait abnormalities), give hydroxocobalamin 1 mg IM on alternate days until no further improvement, then switch to maintenance 4
Maintenance Treatment
- Hydroxocobalamin 1 mg intramuscularly every 2-3 months lifelong 2, 4
- Oral B12 (1,000 µg/day) can be considered for long-term maintenance in patients without malabsorption or pernicious anemia 2
Critical Caveat
Never give folic acid before treating B12 deficiency, as folate can mask B12 deficiency and precipitate subacute combined degeneration of the spinal cord 4. The normal folate level here is reassuring.
Expected Response
- Hemoglobin should increase by at least 2 g/dL within 4 weeks 3
- Hypersegmented neutrophils disappear within 2 weeks of B12 therapy 5
- Reticulocyte count should rise within days, peaking at 5-7 days (indicating bone marrow response)
- Fatigue and other symptoms typically improve within weeks
Follow-Up Investigations
After initiating treatment, investigate the cause of B12 deficiency:
- Intrinsic factor antibodies to diagnose pernicious anemia (most common cause in elderly) 5
- Consider gastric achlorhydria, atrophic gastritis 2
- Review medications (metformin, proton pump inhibitors, H2 blockers) 2
- Assess for malabsorption syndromes if no other cause identified
At age 72, pernicious anemia due to lack of intrinsic factor is the most likely etiology, affecting 10-20% of older adults 2.