Causes of Normal WBC with Increased Neutrophils and Decreased Lymphocytes
A normal white blood cell count with increased neutrophils and decreased lymphocytes (neutrophilia with relative lymphopenia) most commonly occurs in acute stress responses, early bacterial infections, and certain inflammatory conditions where the total WBC remains within normal range despite significant shifts in differential counts.
Common Causes
Acute Stress Response
- Physical stress (surgery, trauma, exercise)
- Emotional stress
- Seizures
- Anesthesia 1
- The stress response causes demargination of neutrophils and redistribution of lymphocytes to lymphoid tissues
Early or Resolving Infections
- Early bacterial infections before significant leukocytosis develops
- Viral infections in early or recovery phases 2
- COVID-19 infection (particularly notable for normal WBC with lymphopenia) 2
Inflammatory Conditions
- Early stages of inflammatory disorders
- Autoimmune diseases
- Tissue injury or necrosis 3
Medication Effects
- Corticosteroids (even a single dose can cause neutrophilia with lymphopenia)
- Beta-agonists
- Epinephrine
- Lithium 1, 4
Physiologic Variations
- Diurnal variation (WBC counts are typically higher in the afternoon)
- Post-exercise state (temporary neutrophilia with relative lymphopenia) 1
Diagnostic Approach
Laboratory Assessment
- Complete blood count with differential
- Calculate absolute neutrophil and lymphocyte counts (not just percentages)
- Neutrophil-to-lymphocyte ratio (NLR) - elevated in stress and inflammation 5
- Look for toxic granulations or band forms suggesting infection 6
Clinical Correlation
- Fever pattern (continuous in bacterial, intermittent in viral)
- Presence of localizing symptoms
- Recent stressors or medication changes
- Duration of symptoms
Special Considerations
Infectious Disease Patterns
- Early bacterial infections may show normal WBC with left shift (increased bands) 2
- Viral infections typically cause lymphocytosis but may initially present with relative lymphopenia 2
- Certain rickettsial diseases can present with normal WBC but altered differentials 2
Hematologic Disorders
- Early stages of certain hematologic disorders before WBC elevation
- Bone marrow recovery phase after suppression
- Myelodysplastic syndromes
Clinical Pitfalls to Avoid
- Don't assume normal WBC excludes infection - differential counts matter
- Don't overlook medication effects, particularly recent steroid use
- Avoid attributing findings solely to stress without excluding infection
- Remember that absolute counts are more meaningful than percentages 7
- Serial measurements may be more informative than a single value
Management Implications
- If bacterial infection is suspected despite normal WBC, look for other signs like elevated C-reactive protein or procalcitonin
- In patients with normal WBC but neutrophilia >90% or band forms >16%, bacterial infection should still be strongly considered 1
- Monitor trends in cell counts rather than relying on a single measurement
- Consider the neutrophil-to-lymphocyte ratio as a marker of inflammation severity 5