What medications can cause elevated white blood cell (WBC) counts and neutrophils?

Medications That Cause Elevated Neutrophils and WBC Counts

Corticosteroids (prednisone, hydrocortisone) are the most common medications that cause significant elevations in white blood cell counts and neutrophils, with increases of up to 4,800 × 10^9/L cells within 48 hours after high-dose administration. 1

Common Medications Causing Leukocytosis

1. Corticosteroids

• Mechanism: Cause demargination of neutrophils from vascular endothelium into circulation and delayed apoptosis of neutrophils

• Magnitude of effect:

  • Prednisone: Mean increase of 4,610 ± 360 neutrophils/mm³ 2
  • Hydrocortisone: Mean increase of 4,220 ± 320 neutrophils/mm³ 2
  • Dose-dependent response: Higher doses cause greater increases 3
  • Peak effect: Usually within 48 hours of administration 1
  • Duration: Can persist for the duration of therapy 3

• Pattern of leukocytosis:

  • Predominantly neutrophilia (increased polymorphonuclear cells)
  • Often accompanied by monocytosis
  • Typically causes eosinopenia
  • Variable lymphopenia 3

2. Colony-Stimulating Factors

• G-CSF (Filgrastim, Pegfilgrastim):
  • Used specifically to increase neutrophil counts
  • Significant elevation of neutrophils expected and intended 4
  • Available as filgrastim, filgrastim-sndz, tbo-filgrastim, and pegfilgrastim 4

3. Other Common Medications

• Beta-agonists: Can cause moderate leukocytosis 5
• Lithium: Associated with leukocytosis, particularly neutrophilia 5
• Azathioprine: Paradoxically can cause leukocytosis in some patients despite being an immunosuppressant 6

Clinical Considerations

Distinguishing Medication-Induced vs. Infection-Induced Leukocytosis

• Medication-induced:

  • Rarely shows "left shift" (>6% band forms)
  • Typically lacks toxic granulation in neutrophils
  • Often predictable timing related to medication administration 3

• Infection-induced:

  • Often shows "left shift" with increased immature neutrophil forms
  • Frequently shows toxic granulation in neutrophils
  • May have other signs/symptoms of infection 3

Monitoring Recommendations

• For patients on corticosteroids:

  • Expect WBC increases of up to 4.84 × 10^9/L within 48 hours after high-dose steroids
  • Larger increases suggest other causes of leukocytosis 1
  • WBC counts should be drawn before morning steroid dose for accurate baseline 6

• For patients on G-CSF:

  • Weekly blood counts recommended for the first 6 months
  • Discontinue if WBC <2,000/mm³ or ANC <1,000/mm³ 4

Special Populations

• Transplant recipients:

  • Individual WBC response to steroids is reproducible but varies between patients
  • Not correlated with steroid dose but consistent for each patient 6

• Patients with hematologic conditions:

  • Avoid medications that can lower blood counts (e.g., carbamazepine) in patients with pre-existing neutropenia 7

Important Caveats

• Extremely high WBC counts (>100,000/mm³) are unlikely to be medication-induced alone and represent a medical emergency due to risk of brain infarction and hemorrhage 5
• Even small doses of prednisone administered over prolonged periods can induce extreme and persistent leukocytosis 3
• Medication-induced leukocytosis can complicate the diagnosis of infection, particularly in immunocompromised hosts 3

When evaluating elevated WBC and neutrophil counts, always consider the patient's medication list, particularly recent initiation or dose changes of corticosteroids or colony-stimulating factors, before pursuing extensive infectious workup.