What medications can increase white blood cell (WBC) count?

Medications That Can Increase White Blood Cell Count

Filgrastim (G-CSF) is the most effective medication for increasing white blood cell count, particularly neutrophils, with increases typically occurring within 24 hours of administration. 1

First-Line Medications

Granulocyte Colony-Stimulating Factors (G-CSFs)

• Filgrastim (Zarxio, Neupogen):
  • Mechanism: Directly stimulates neutrophil production and release from bone marrow
  • Typical increase: Can raise WBC count by 10-30 × 10⁹/L within 24-48 hours
  • Dosage: 5-10 μg/kg/day subcutaneously
  • Monitoring: CBC with differential should be monitored regularly during therapy
  • Caution: Discontinue if WBC exceeds 100,000/mm³ 1

Corticosteroids

• Prednisone/Prednisolone:
  • Mechanism: Demargination of neutrophils from vessel walls into circulation
  • Typical increase:
    • Low dose (≤20mg): 0.3 × 10⁹/L increase
    • Medium dose (21-40mg): 1.7 × 10⁹/L increase
    • High dose (>40mg): 4.8 × 10⁹/L increase 2
  • Peak effect: Within 48 hours of administration
  • Duration: Persists throughout treatment period, can last weeks 3
  • Note: Even small doses administered over prolonged periods can induce significant leukocytosis 3

Second-Line Options

Inhaled Corticosteroids

• Budesonide and Fluticasone:
  • Mechanism: Decrease expression of neutrophil adhesion molecules (Mac-1 and L-selectin)
  • Effect: Budesonide increases WBC by 23.4% and ANC by 30.1%; Fluticasone increases WBC by 12.6% and ANC by 22.7%
  • Onset: Effects seen within 6 hours of a single dose 4

Immunomodulators

• Azathioprine:
  • Paradoxical effect: While typically causing leukopenia, in some cases it may be continued despite WBC counts <7,000/mm³ 5
  • Note: Requires close monitoring as it typically decreases rather than increases WBC count

Clinical Considerations

Monitoring Parameters

• For patients receiving G-CSFs:
  • Monitor CBC at least twice weekly during therapy
  • Discontinue if WBC count exceeds 100,000/mm³ 6
  • Watch for potential side effects including bone pain, capillary leak syndrome, and splenic rupture

Steroid-Induced Leukocytosis vs. Infection

• Steroid-induced leukocytosis:
  • Typically lacks left shift (band forms <6%)
  • Rarely shows toxic granulation
  • Usually peaks within 48 hours of administration 3
  • Average increase of 5 × 10⁹/L in chronically treated patients with acute infections 7

Cautions and Contraindications

• G-CSFs are contraindicated in patients with:
  • History of serious allergic reactions to filgrastim products
  • Sickle cell disorders (can precipitate crisis)
  • Underlying malignancies (potential stimulation of tumor growth) 1

Algorithm for Medication Selection

1. Assess urgency and target WBC level needed:

   • Rapid increase needed (24-48 hours): Choose filgrastim
   • Moderate increase acceptable (48-72 hours): Consider corticosteroids
   • Mild increase sufficient: Consider inhaled corticosteroids

2. Consider underlying conditions:

   • Neutropenia post-chemotherapy: Filgrastim preferred
   • Inflammatory conditions: Corticosteroids may provide dual benefit
   • Respiratory conditions: Inhaled corticosteroids may be appropriate

3. Monitor response:

   • Check CBC within 24-48 hours of initiating therapy
   • Adjust dosing based on response and target WBC count
   • Discontinue G-CSFs if WBC exceeds 100,000/mm³

When interpreting WBC increases after steroid initiation, increases up to 4.8 × 10⁹/L within 48 hours after high-dose steroids are expected. Larger increases, or any significant increase after low-dose steroids, should prompt investigation for other causes of leukocytosis such as infection 2.