What is the likely diagnosis and management for a patient with leukocytosis and neutrophilia?

Evaluation of Leukocytosis with Marked Neutrophilia

This patient presents with moderate leukocytosis (WBC 10.6 × 10⁹/L) and marked neutrophilia (84.9%, absolute neutrophil count 9.0 × 10⁹/L), which most commonly indicates an acute bacterial infection requiring immediate clinical correlation with fever, localizing symptoms, and inflammatory markers to guide management. 1

Clinical Significance and Differential Diagnosis

Infection as Primary Consideration

• Bacterial infection is the most likely diagnosis when neutrophilia accompanies leukocytosis, particularly when the absolute neutrophil count exceeds 7.5 × 10⁹/L 1, 2
• Blood cultures should be obtained immediately if the patient has fever, chills, hypothermia, signs of hemodynamic compromise, or suspected infection 1
• The combination of neutrophilic leukocytosis with elevated CRP (>40 mg/L) or fever (>38.5°C) shows high specificity for bacterial infection 2

Important Non-Infectious Causes to Exclude

Stress-related leukocytosis can occur from:

• Surgery, trauma, exercise, or emotional stress (can double WBC within hours) 3
• Medications (corticosteroids, lithium, beta-agonists) 3
• Smoking and obesity 3

Thrombotic conditions:

• Leukocytosis and neutrophilia are commonly observed in patients with thrombosis, including heparin-induced thrombocytopenia 4
• This finding should not automatically suggest infection when evaluating patients with thrombocytopenia or thrombotic events 4

Inflammatory conditions:

• Adult-onset Still's disease presents with marked leukocytosis (50% of patients have WBC >15 × 10⁹/L, 37% have WBC >20 × 10⁹/L) along with fever and rash 1
• Chronic inflammatory conditions can cause persistent neutrophilia 3

Diagnostic Approach

Immediate Assessment Required

1. Clinical evaluation for infection sources:

   • Fever pattern, chills, or hypothermia 1
   • Localizing symptoms (respiratory, urinary, abdominal, skin/soft tissue) 1
   • Signs of hemodynamic compromise or sepsis 1

2. Laboratory workup:

   • Blood cultures (at least 2 sets) if infection suspected 1
   • C-reactive protein and procalcitonin levels (PCT ≥1.5 ng/mL has 100% sensitivity for sepsis) 1
   • Comprehensive metabolic panel to assess for renal failure or hypoalbuminemia (both associated with bacteremia) 1

3. Peripheral blood smear examination:

   • Assess for left shift (immature neutrophils), toxic granulations, or band forms 1
   • Evaluate white blood cell morphology and maturity 3
   • Look for eosinopenia (deep eosinopenia with >94% specificity for infection) 2

Risk Stratification

High-risk features suggesting serious infection or malignancy:

• Fever with leukocytosis 1
• Constitutional symptoms (weight loss, night sweats, fatigue) 3
• Bruising or bleeding 3
• Persistent or progressive leukocytosis 3

Prognostic considerations:

• Marked neutrophilia or failure to mount neutrophil response may have prognostic value in sepsis 1
• In one veterinary study extrapolated to clinical context, leukocytosis >50 × 10⁹/L with neutrophilia >50% was associated with high mortality 5

Management Recommendations

If Infection is Suspected

Immediate empiric antibiotics should be initiated if:

• Patient is febrile with signs of sepsis 1
• Clinical evidence of bacterial infection with hemodynamic compromise 1
• Antibiotic selection should target gram-negative organisms (E. coli, Klebsiella, Pseudomonas) and gram-positive organisms based on clinical presentation 1

If Malignancy Cannot be Excluded

Referral to hematology/oncology is indicated when: 3

• Constitutional symptoms present (fever, weight loss, bruising, fatigue)
• No clear infectious or inflammatory cause identified
• Persistent or progressive leukocytosis despite treatment of presumed infection

Serial Monitoring

• Daily sequential measurement of inflammatory markers (CRP, PCT) is more valuable than single measurements for diagnosing and monitoring infection 1
• Repeat complete blood count with differential in 24-48 hours if initial cause unclear 3
• Monitor for resolution with treatment of underlying cause 1

Common Pitfalls to Avoid

• Do not assume infection automatically: Leukocytosis can occur with thrombosis, stress, medications, or inflammatory conditions without infection 3, 4
• Do not delay blood cultures: Bacteria are rapidly cleared from blood; cultures should be obtained immediately after fever onset, ideally before antibiotics 1
• Do not ignore clinical context: The absolute neutrophil count of 9.0 × 10⁹/L is elevated but not extreme; clinical correlation with symptoms and inflammatory markers is essential 1, 2
• Consider leukocyte adhesion defect if marked leukocytosis persists even without ongoing infection 1