What are the treatment options for elevated white blood cell (WBC) count and suspected vitamin B12 deficiency?

Management of Elevated White Blood Cell Count and Vitamin B12 Deficiency

For patients with elevated white blood cell count and suspected vitamin B12 deficiency, treatment should focus on addressing the underlying cause of leukocytosis while simultaneously correcting B12 deficiency with either oral supplementation (1000 μg daily) or intramuscular injections (1000 μg monthly) depending on the cause of deficiency.

Diagnostic Approach

Initial Assessment for B12 Deficiency

• Use either total B12 (serum cobalamin) or active B12 (serum holotranscobalamin) as the initial test 1
• Interpret results according to these thresholds:
  • Confirmed deficiency: Total B12 <180 ng/L (133 pmol/L) or active B12 <25 pmol/L
  • Indeterminate: Total B12 180-350 ng/L (133-258 pmol/L) or active B12 25-70 pmol/L
  • Unlikely deficiency: Total B12 >350 ng/L (258 pmol/L) or active B12 >70 pmol/L 1

Confirmatory Testing

• For indeterminate results, measure serum methylmalonic acid (MMA) to confirm B12 deficiency 1, 2
• Complete blood count should be obtained to assess for megaloblastic anemia 3

Evaluation of Elevated WBC Count

• Rule out acute myeloid leukemia (AML) or other hematologic malignancies, which can present with both elevated WBC and B12 deficiency 1, 4
• Note that hypervitaminosis B12 can be associated with leukemia and bone marrow dysplasia 4

Treatment Algorithm

1. For Confirmed B12 Deficiency with Malabsorption:

Option A: Intramuscular (IM) Administration

• Initial loading: 100 mcg daily for 6-7 days by IM injection
• Followed by: 100 mcg on alternate days for 7 doses
• Then: 100 mcg every 3-4 days for 2-3 weeks
• Maintenance: 100 mcg monthly for life 5

Option B: High-Dose Oral Administration

• 1000-2000 μg (1-2 mg) daily oral cyanocobalamin 2, 3
• This approach is as effective as IM administration for most patients, even those with malabsorption 3

2. For B12 Deficiency with Normal Absorption:

• Oral supplementation with 1000 μg daily is appropriate 2, 3

3. Special Populations:

• Post-bariatric surgery: 1000 μg oral B12 daily indefinitely 2
• Vegans/vegetarians: 250-350 μg daily or 1000 μg weekly 2
• Patients with pernicious anemia: Lifelong monthly IM injections of 100 mcg 5

Monitoring Response

B12 Deficiency Monitoring

• Monitor hematocrit and reticulocyte counts daily from days 5-7 of therapy until hematocrit normalizes 5
• Reassess B12 levels after 1-3 months of supplementation 2
• Annual assessment of B12 status for patients on maintenance therapy 2

Leukocytosis Monitoring

• If AML is diagnosed, follow specific protocols for management 1
• For APL (Acute Promyelocytic Leukemia) with high WBC count:
  • Leukapheresis is not routinely recommended but can be considered in life-threatening cases with leukostasis 1
  • Monitor for APL differentiation syndrome (fever, WBC >10,000/mcL, shortness of breath, hypoxemia, pleural/pericardial effusions) 1

Important Precautions

• B12 deficiency left untreated for >3 months may produce permanent degenerative spinal cord lesions 5
• High-dose folic acid (>0.1 mg/day) may mask B12 deficiency hematologically but won't prevent neurological damage 5
• Avoid intravenous administration of B12 as most will be lost in urine 5
• For patients with elevated WBC counts and APL, central venous catheter placement should be delayed until bleeding is controlled 1

Follow-up

• If reticulocytes don't increase after treatment or don't maintain at least twice normal levels while hematocrit is <35%, reevaluate diagnosis or treatment 5
• Patients with pernicious anemia have approximately three times the risk of stomach cancer and should undergo appropriate testing when indicated 5

By following this algorithm, clinicians can effectively manage both the elevated white blood cell count and vitamin B12 deficiency, prioritizing interventions that will improve morbidity, mortality, and quality of life outcomes.