Can B12 or Folate Deficiency Cause Low WBC?
Yes, both vitamin B12 and folate deficiency can cause leukopenia (low white blood cell count) as part of pancytopenia, a condition where all blood cell lines are reduced. 1, 2
Mechanism and Presentation
B12 and folate deficiencies cause megaloblastic anemia with pancytopenia, meaning they affect not just red blood cells but also white blood cells and platelets 1. The pancytopenia occurs because these vitamins are essential for DNA synthesis in all rapidly dividing cells, including bone marrow precursors 1.
Key Clinical Features:
- Pancytopenia includes low hemoglobin, low WBC (leukopenia), and low platelets (thrombocytopenia) 1, 2
- Macrocytic anemia (MCV >100 fL) is typically present but not always 1, 3
- Severe cases can present with profound cytopenias: one documented case showed WBC of 3.2 × 10⁹/L with hemoglobin of 2.6 g/dL and platelets of 17 × 10⁹/L 2
Critical Diagnostic Pitfall
The most dangerous scenario is high folate with low B12, which can mask the hematological manifestations (including low WBC) while allowing irreversible neurological damage to progress 1, 4, 5, 6. This occurs because:
- Folic acid supplementation can correct the blood picture (including WBC counts) in B12 deficiency 1, 5, 6
- Neurological manifestations will worsen despite hematological improvement 1, 5
- Doses of folic acid >0.1-0.4 mg daily can produce hematologic remission while neurological damage becomes irreversible 5, 6
Diagnostic Approach
When evaluating low WBC with suspected nutritional deficiency:
- Always measure both B12 and folate simultaneously when investigating cytopenias 1, 7
- Check MCV first: Macrocytosis (MCV >100 fL) suggests B12/folate deficiency, but normocytic anemia can occur in 9.2% of cases with B12/folate deficiency 1, 3
- Measure homocysteine if B12/folate levels are borderline, as it has better sensitivity than serum B12 alone 1, 8
- Never give folic acid before excluding B12 deficiency 1, 5, 6, 7
Treatment Priorities
If B12 deficiency is confirmed or suspected with low WBC:
- Treat B12 deficiency immediately before initiating folic acid 1, 5, 6
- For neurological involvement: hydroxocobalamin 1 mg IM on alternate days until no further improvement, then every 2 months 1
- For no neurological involvement: hydroxocobalamin 1 mg IM three times weekly for 2 weeks, then maintenance every 2-3 months lifelong 1
If folate deficiency is confirmed (after excluding B12 deficiency):
- Oral folic acid 1-5 mg daily for minimum 4 months 1
- Rapid improvement in leukopenia and thrombocytopenia typically occurs within days to weeks 2
Common Clinical Scenarios
Normocytic anemia with low WBC: Don't assume normal MCV excludes B12/folate deficiency—9.2% of patients with B12/folate deficiency present with normocytic anemia and may have leukopenia 3
Patients on certain medications: Methotrexate, sulfasalazine, and anticonvulsants can cause folate deficiency leading to pancytopenia 1
Post-bariatric surgery: These patients are at high risk for B12 and folate deficiency causing cytopenias and require regular monitoring 1