In a 71‑year‑old man with leukopenia (white blood cell count 2.9 ×10⁹/L), anemia (hemoglobin 12.3 g/dL, red blood cell count 4.08 ×10¹²/L), neutropenia (absolute neutrophil count 1.2 ×10⁹/L) and low serum vitamin B12 (154 pg/mL), what is the next step in management?

Management of Vitamin B12 Deficiency with Cytopenias

Immediate intramuscular vitamin B12 1000 µg should be started without delay in this patient with confirmed severe B12 deficiency (154 pg/mL), leukopenia, neutropenia, and anemia. 1, 2

Diagnostic Confirmation

• The serum B12 of 154 pg/mL is definitively deficient, falling well below the diagnostic threshold of 180 pg/mL (133 pmol/L). 1
• No additional confirmatory testing (MMA, homocysteine, or intrinsic factor antibodies) is required before initiating treatment when B12 is <180 pg/mL with cytopenias. 1
• The presentation of pancytopenia (leukopenia with WBC 2.9, neutropenia with ANC 1.2, and anemia with hemoglobin 12.3) is consistent with severe B12 deficiency causing ineffective hematopoiesis. 3

Immediate Treatment Protocol

Intramuscular hydroxocobalamin or cyanocobalamin 1000 µg should be administered immediately using the following regimen: 1, 2

• Days 1–14: 1000 µg IM three times weekly (or daily for 6–7 days per FDA labeling). 1, 2
• Weeks 3–4: Continue 1000 µg IM on alternate days for seven doses. 2
• Weeks 5–7: 1000 µg IM every 3–4 days for another 2–3 weeks. 2
• Maintenance: 1000 µg IM monthly for life once hematologic parameters normalize. 1, 2

Oral high-dose B12 (1000–2000 µg daily) is equally effective for most patients, but intramuscular therapy is preferred in this case given the severity of cytopenias and should be considered when neutropenia or significant anemia is present. 1, 4, 5

Critical Monitoring Parameters

Reticulocyte count should be checked between days 5–10 to confirm therapeutic response; reticulocytosis indicates appropriate bone marrow recovery. 2, 5

Complete blood count should be repeated on days 10,30, and 90 to document normalization of hemoglobin, WBC, neutrophils, and platelets. 5

• Expected response includes reticulocytosis within 5–10 days, rising hemoglobin and WBC counts by day 30, and complete normalization by day 90. 5
• Failure to achieve reticulocytosis suggests an alternative or additional diagnosis requiring hematology consultation. 6

Essential Concurrent Workup

Check folate level immediately before starting therapy, as deficiencies often coexist and folate must never be given alone before B12 replacement. 1, 2

• Administering folic acid before treating B12 deficiency can precipitate subacute combined degeneration of the spinal cord by masking anemia while allowing irreversible neurological damage to progress. 1

Complete iron studies (ferritin, transferrin saturation, CRP) should be obtained to identify concurrent iron deficiency, which is common and may require separate treatment. 6

Assess for neurological symptoms including paresthesias, numbness, balance problems, cognitive difficulties, or visual changes, as these may occur even before anemia develops and require more aggressive initial dosing. 1

• If neurological involvement is present, use 1000 µg IM on alternate days until no further improvement, then 1000 µg IM every 2 months for life. 1

Identify Underlying Cause

Investigate the etiology of B12 deficiency to guide long-term management: 1, 4

• Dietary history: Vegan/vegetarian diet, food allergies to eggs/milk/fish. 1
• Medication review: Metformin >4 months, PPIs or H2 blockers >12 months, colchicine, phenobarbital, pregabalin. 1
• Gastrointestinal conditions: History of gastric/small bowel resection, inflammatory bowel disease (especially ileal Crohn's disease >20 cm resection), celiac disease, atrophic gastritis. 1, 4
• Autoimmune screening: Check for thyroid disease, type 1 diabetes, Sjögren syndrome, as these increase risk. 1

Intrinsic factor antibody testing can be performed but should not delay treatment; positive results confirm pernicious anemia requiring lifelong IM therapy. 1

Common Pitfalls to Avoid

Do not wait for additional test results before starting treatment when B12 is <180 pg/mL with cytopenias; immediate therapy is mandatory. 1

Do not use the intravenous route, as almost all vitamin will be lost in urine; intramuscular or deep subcutaneous injection is required. 2

Do not misinterpret severe B12 deficiency as acute leukemia or myelodysplastic syndrome; the profound dysplastic changes, hypersegmented neutrophils, and hypercellular bone marrow with blastic differentiation can mimic hematologic malignancy. 3

Do not discontinue treatment after initial improvement; lifelong maintenance therapy is required because the underlying malabsorption typically persists. 1, 2

Expected Clinical Course

Hematologic improvement should be evident by day 30, with complete normalization by day 90 in most patients. 5

Neurologic symptoms improve in approximately 75–78% of patients by day 30 if present, though some deficits may be irreversible if treatment is delayed. 1, 5

Serum B12 levels should normalize by day 90 and remain elevated with appropriate maintenance therapy. 5