What is the appropriate treatment for a patient with vitamin B12 deficiency presenting with macrocytic anemia (serum cobalamin 142 pg/mL, hemoglobin 117 g/L, macrocytosis, large platelets and polychromasia)?

Treatment of Confirmed Vitamin B12 Deficiency with Macrocytic Anemia

This patient has confirmed vitamin B12 deficiency (142 pg/mL is below the 180 pg/mL threshold) with macrocytic anemia and should be treated immediately with intramuscular vitamin B12 without waiting for additional testing. 1

Diagnostic Confirmation

Your patient's presentation is classic for B12 deficiency:

• Serum B12 of 142 pg/mL (approximately 105 pmol/L) is definitively deficient, falling well below the 180 pg/mL (133 pmol/L) diagnostic threshold 1, 2
• Macrocytosis with polychromasia and large platelets are characteristic hematologic findings of megaloblastic anemia 3, 4
• No further confirmatory testing (MMA or homocysteine) is needed when B12 is this low—these tests are reserved only for indeterminate results (180-350 pg/mL) 1, 2

The polychromasia indicates some reticulocyte response, though typically B12 deficiency shows a low reticulocyte count due to ineffective erythropoiesis 3, 5. The hemoglobin of 117 g/L represents moderate anemia requiring prompt treatment.

Immediate Treatment Protocol

Initial Intensive Phase

Administer hydroxocobalamin or cyanocobalamin 1000 mcg (1 mg) intramuscularly:

• Daily for 6-7 days initially to rapidly replete stores 6
• Then alternate days for seven doses (2 weeks) if clinical improvement and reticulocyte response occur 6
• Then every 3-4 days for another 2-3 weeks until hematologic values normalize 6

Critical: Avoid the intravenous route—almost all vitamin will be lost in urine 6. Use intramuscular or deep subcutaneous injection only 6.

Maintenance Therapy

After normalization of hematologic parameters, continue with 1000 mcg intramuscularly monthly for life 6, 7. This lifelong treatment is essential because the underlying cause (likely malabsorption) will persist 1.

Alternative Oral Therapy Consideration

While the FDA label emphasizes parenteral therapy for malabsorption 6, recent guidelines show oral B12 (1000-2000 mcg daily) is equally effective for most patients, including those with malabsorption, and is more cost-effective 2. However, given the moderate anemia (Hgb 117 g/L) and need for rapid repletion, starting with intramuscular therapy is preferred, with potential transition to high-dose oral maintenance after initial correction 2, 8.

Essential Concurrent Assessments

Rule Out Folate Deficiency

Check serum folate levels immediately 8, 9. If folate is also deficient, never give folic acid before or without B12 treatment—this can mask the anemia while allowing irreversible neurological damage to progress 8. If both are deficient, treat both simultaneously 6, 5.

Assess for Neurological Involvement

Actively screen for neurological symptoms including:

• Paresthesias, numbness, or peripheral neuropathy 2, 10
• Cognitive difficulties, memory problems, or concentration issues 2
• Gait disturbances or proprioceptive deficits 2

If any neurological symptoms are present, use a more aggressive regimen: hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then maintenance every 2 months for life 2. Neurological damage can become irreversible if untreated 8, 10.

Identify the Underlying Cause

Investigate why this patient is B12 deficient:

• Test for pernicious anemia: anti-intrinsic factor antibodies (most specific) and anti-parietal cell antibodies 7, 10
• Medication review: metformin >4 months, PPIs/H2 blockers >12 months, colchicine, anticonvulsants 2
• Dietary history: strict vegan diet without supplementation 2
• Gastrointestinal causes: atrophic gastritis, ileal resection >20 cm, Crohn's disease, celiac disease 2, 8
• Consider Schilling test if malabsorption mechanism needs clarification 6

Monitoring Response to Treatment

Expected Hematologic Response

• Reticulocyte count should rise within 3-7 days of starting treatment 6, 5
• Hemoglobin should begin improving within 1-2 weeks 7
• Complete normalization of blood counts typically occurs within 6-8 weeks 6

Follow-Up Laboratory Testing

Recheck complete blood count and B12 level at:

• 3 months to confirm normalization 2
• 6 months to ensure sustained response 2
• Then annually for life to detect treatment failures 2

Target B12 level >300 pmol/L (approximately 400 pg/mL) for optimal health 2, though some guidelines suggest even higher targets of 30-44 ng/mL (220-325 pmol/L) for cardiovascular and musculoskeletal benefits 2.

Critical Pitfalls to Avoid

Do Not Delay Treatment

With B12 <180 pg/mL and macrocytic anemia, treatment should begin immediately—do not wait for MMA, homocysteine, or intrinsic factor antibody results 1, 2. These can be sent concurrently but should not delay therapy.

Watch for Severe Presentations

This patient's presentation is relatively mild, but be aware that severe B12 deficiency can mimic thrombotic thrombocytopenic purpura with:

• Marked thrombocytopenia (platelets <50×10⁹/L) 7, 4
• Extremely elevated LDH (>2500 IU/L, sometimes >9000 IU/L) 7, 4
• Schistocytes on peripheral smear (pseudothrombotic microangiopathy) 7, 10

Key distinguishing feature: reticulocyte count is LOW in B12 deficiency (<2.5%) versus elevated in true TTP 7. LDH >2500 IU/L is more typical of B12 deficiency than TTP 7.

Monitor for Hypokalemia

During the first week of treatment, rapid cell production can cause hypokalemia—monitor potassium levels, especially if the patient has cardiac disease 9.

Ensure Lifelong Compliance

Emphasize that this is lifelong therapy—patients often feel better after initial treatment and discontinue maintenance injections, leading to recurrence 2, 6. If malabsorption is the cause (pernicious anemia, ileal resection, bariatric surgery), oral supplementation alone will not suffice without high doses 2, 8.