What is the appropriate follow-up for a 51-year-old male with leukocytosis (elevated White Blood Cell (WBC) count), neutrophilia (elevated neutrophil level), mild hyponatremia (low sodium level), and mild hypochloremia (low chloride level), without a known source of infection?

Appropriate Follow-Up for Leukocytosis Without Identified Infection Source

This patient requires immediate clinical assessment for occult bacterial infection, as the WBC count of 14,500 cells/mm³ with neutrophilia carries a likelihood ratio of 3.7 for underlying bacterial infection, even without fever or obvious source. 1, 2

Immediate Diagnostic Workup

Essential Laboratory Studies

• Manual differential count is mandatory to assess for left shift (≥16% band neutrophils), which has a likelihood ratio of 4.7 for bacterial infection even when total WBC is only mildly elevated 2, 3
• Absolute band count should be calculated—if ≥1,500 cells/mm³, this carries the highest likelihood ratio (14.5) for documented bacterial infection 2, 3
• Blood cultures should be obtained if any signs of systemic infection are present (fever, hypotension, tachycardia, altered mental status) 2, 4
• Urinalysis with culture to exclude urinary tract infection, as UTI is a common occult source in adults 2

Critical Clinical Assessment

Evaluate for the following infection sources and sepsis criteria:

• Vital signs: Check for fever >38°C or hypothermia <36°C, hypotension <90 mmHg systolic, tachycardia, tachypnea 3, 4
• Respiratory symptoms: Cough, dyspnea, chest pain suggesting pneumonia 3
• Urinary symptoms: Dysuria, flank pain, frequency 3
• Skin/soft tissue: Erythema, warmth, purulent drainage 3
• Abdominal examination: Peritoneal signs, diarrhea suggesting intra-abdominal infection 2
• Lactate level: If >3 mmol/L, indicates severe sepsis requiring immediate intervention 4

Electrolyte Abnormalities

The mild hyponatremia (133 mEq/L) and hypochloremia (95 mEq/L) are non-specific but may indicate:

• Volume depletion from occult infection
• SIADH from pulmonary or CNS infection
• These findings do not change the primary focus on identifying infection source 2

Management Algorithm

If Patient is Hemodynamically Stable:

1. Complete diagnostic workup first before initiating antibiotics 3, 4
2. Obtain chest X-ray if any respiratory symptoms present 2
3. Site-specific cultures as clinically indicated 2
4. Close monitoring for clinical deterioration 3

If Sepsis Criteria Present:

1. Initiate broad-spectrum empiric antibiotics within 1 hour of recognition 3, 4
2. Aggressive fluid resuscitation for hypotension 3, 4
3. Vasopressor support if hypotension persists despite fluids 3, 4
4. Source control measures (drainage of abscesses, removal of infected catheters) 3

Alternative Considerations if Infection Excluded

If thorough evaluation reveals no infection source, consider:

• Medications: Corticosteroids, lithium, beta-agonists can cause leukocytosis 2, 5
• Physical or emotional stress: Surgery, trauma, exercise, emotional stress can double WBC count within hours 5, 6
• Smoking and obesity: Common non-infectious causes 5
• Chronic inflammatory conditions 5
• Persistent inflammation-immunosuppression and catabolism syndrome (PICS): Consider if patient has recent major trauma, surgery, or critical illness 7

Critical Pitfalls to Avoid

• Do not ignore elevated neutrophil count when total WBC is only mildly elevated—left shift can occur with normal WBC and still indicate serious bacterial infection 2, 3
• Do not rely on automated analyzer alone—manual differential is essential to assess band forms and immature neutrophils 3, 4
• Do not delay antibiotics in severe sepsis/septic shock while awaiting culture results 3, 4
• Do not treat based solely on laboratory findings without clinical correlation if patient is asymptomatic and hemodynamically stable 3, 4

When to Consider Hematology Referral

Referral to hematology/oncology is indicated if:

• WBC count >100,000 cells/mm³ (medical emergency) 6
• Concurrent abnormalities in red blood cells or platelets 5, 6
• Constitutional symptoms: Fever, weight loss, bruising, fatigue without identified infection 5, 6
• Persistent unexplained leukocytosis after thorough infection workup 5, 8