Prednisone Increases WBC and Neutrophils
Yes, prednisone consistently and predictably increases both white blood cell (WBC) and neutrophil counts through a well-established, dose-dependent mechanism that begins as early as the first day of treatment. 1, 2
Mechanism and Timing
- Corticosteroids like prednisone cause leukocytosis through lymphocyte depletion while simultaneously increasing neutrophil counts, creating a characteristic pattern of neutrophilia with lymphopenia. 1
- The WBC elevation can occur within 6-24 hours of administration and persists throughout the duration of therapy. 1
- Even small doses of prednisone (as low as 0.5 mg/kg/day) administered over prolonged periods can induce extreme and persistent leukocytosis, with WBC counts exceeding 20,000/mm³ as early as the first day of treatment. 2
Magnitude and Pattern of Response
- Standard doses of prednisone (40 mg) or hydrocortisone (200 mg) increase blood neutrophil counts by approximately 4,000-4,600 cells/mm³ above baseline. 3
- Leukocytosis typically reaches maximal values within two weeks, after which the WBC count may decrease slightly but does not return to pretreatment levels while therapy continues. 2
- The leukocytosis is predominantly neutrophilic (27% increase in leukocytes, 33% increase in neutrophils), accompanied by monocytosis, eosinopenia, and variable lymphopenia. 2, 4
Dose-Response Relationship
- Higher doses produce earlier and more pronounced leukocytosis, though the relationship is not strictly linear. 2
- Doses as low as 5-10 mg prednisone produce measurable effects, while doses of 40-80 mg produce maximal neutrophilic responses. 3
- The effect is sustained throughout treatment duration—standard ITP treatment with prednisone 0.5-2 mg/kg/day for 2-4 weeks produces consistent leukocytosis throughout the entire treatment period. 1
Clinical Implications for Infection Diagnosis
When evaluating for infection in patients on prednisone, do not rely solely on the WBC count—instead, check the peripheral smear for left shift (>6% bands) and toxic granulation. 1, 2
- Corticosteroid-induced leukocytosis rarely shows left shift or toxic granulation, whereas infection typically presents with both findings. 2
- Investigate for infection if WBC >14,000/mm³ with left shift (>6% bands), regardless of steroid dose. 1
- Serial monitoring of WBC counts with differential is necessary if infection is suspected, rather than relying on a single elevated value. 1
Duration-Based Risk Stratification
- Any dose for less than 1 week carries low risk for significant immunosuppression but still produces measurable leukocytosis. 1
- Moderate-to-high dose prednisone (≥20 mg/day) for 4 weeks or more produces sustained leukocytosis and increases infection risk, warranting consideration for Pneumocystis jirovecii prophylaxis. 1
- The leukocytosis persists as long as therapy continues, making it an unreliable marker for infection monitoring in patients on chronic steroids. 2
Important Caveats
Leukocytosis may be blunted or absent in severely immunocompromised patients, making infection diagnosis more challenging in this subset. 1
Prednisone decreases C-reactive protein (CRP) levels by approximately 46% but does not affect procalcitonin (PCT) levels, making PCT a more reliable marker for infection resolution in patients on corticosteroids. 4