What does Leukocytosis indicate?

Leukocytosis: Clinical Significance and Diagnostic Approach

A WBC count of 20,000/mm³ indicates leukocytosis and strongly suggests an underlying bacterial infection requiring immediate clinical evaluation, with the highest diagnostic priority being identification of the infection source through targeted testing based on symptoms and physical findings. 1

Immediate Clinical Significance

Leukocytosis with WBC ≥14,000/mm³ carries a likelihood ratio of 3.7 for bacterial infection and warrants careful assessment even without fever. 2 When the WBC reaches 20,000/mm³, the probability of serious bacterial infection increases substantially, particularly when combined with other markers. 1

Key Diagnostic Markers to Assess

The most powerful laboratory indicators for bacterial infection, in order of diagnostic accuracy, are: 2

• Absolute band count ≥1,500 cells/mm³ (likelihood ratio 14.5 for bacterial infection)
• Neutrophil percentage >90% (likelihood ratio 7.5)
• Left shift ≥16% bands (likelihood ratio 4.7, even with normal WBC)
• Total WBC ≥14,000/mm³ (likelihood ratio 3.7)

A manual differential count is essential—automated analyzers are insufficient for accurately assessing band forms and immature neutrophils. 3, 4

Most Common Causes at This WBC Level

Infectious Etiologies (Most Likely)

Bacterial infections represent the most common cause of leukocytosis at this level: 2, 5

• Respiratory tract infections (pneumonia, bronchitis)
• Urinary tract infections (pyelonephritis, complicated UTI)
• Skin and soft tissue infections (cellulitis, abscess)
• Gastrointestinal infections (appendicitis, cholecystitis, diverticulitis)
• Bloodstream infections (bacteremia, sepsis)

Non-Infectious Causes to Consider

Physical and emotional stress can double the WBC count within hours due to demargination of neutrophils from bone marrow storage pools. 5, 6 Common non-infectious causes include:

• Medications: Corticosteroids, lithium, beta-agonists, epinephrine 2, 6
• Physiologic stress: Surgery, trauma, seizures, exercise 5, 6
• Chronic conditions: Obesity, smoking, chronic inflammatory diseases 5
• Tissue damage: Major trauma, cerebrovascular accident, myocardial infarction 7

Immediate Diagnostic Workup

Essential First Steps

Obtain a complete blood count with manual differential immediately to assess band forms, neutrophil percentage, and presence of left shift. 1, 4

Symptom-Directed Testing

Respiratory symptoms: 4

• Pulse oximetry
• Chest radiograph (mandatory if hypoxemia documented)
• Consider thoracic ultrasound if chest X-ray abnormal

Urinary symptoms: 3, 4

• Urinalysis for leukocyte esterase/nitrite
• Microscopic examination for WBCs
• Urine culture if pyuria present (≥10 WBCs/high-power field)

Abdominal symptoms: 4

• Abdominal ultrasound or CT if indicated by examination
• Consider diagnostic paracentesis in patients with ascites

Skin/soft tissue findings: 3

• Needle aspiration or deep-tissue biopsy if fluctuant areas present or unusual pathogens suspected

Blood Cultures

Blood cultures should be obtained if bacteremia is suspected based on: 3, 4

• High fever with rigors
• Hemodynamic instability
• Suspected endocarditis or intravascular infection
• No clear localized source identified

Critical Thresholds and Red Flags

Hyperleukocytosis (WBC >100,000/mm³)

WBC counts above 100,000/mm³ represent a medical emergency due to risk of leukostasis, cerebral infarction, and hemorrhage, requiring immediate cytoreduction with hydroxyurea. 1 However, at WBC 20,000/mm³, this is not an immediate concern.

Occult Pneumonia Consideration

In highly febrile children (>39°C) with WBC >20,000/mm³ and no respiratory findings, consider chest radiograph as occult pneumonia occurs in approximately 26% of such cases. 1 This applies to children older than 3 months.

Common Pitfalls to Avoid

Do not ignore left shift when total WBC is only mildly elevated—a left shift ≥16% bands indicates significant bacterial infection even with normal total WBC count. 2, 3

Do not rely solely on automated differential counts—manual review is essential for accurate band assessment and detection of toxic granulations or immature forms. 1, 3

Do not treat asymptomatic bacteriuria in patients with chronic catheters—virtually 100% have bacteriuria and pyuria without infection. 1

Do not assume infection is the only cause—consider medication effects (especially corticosteroids), recent surgery or trauma, and chronic inflammatory conditions before initiating antibiotics. 5, 6

Special Population Considerations

Older Adults in Long-Term Care

In elderly patients, leukocytosis has been associated with increased mortality from pneumonia and bloodstream infections, and typical infection symptoms are frequently absent due to decreased basal body temperature and frailty. 1, 3

Hospitalized Patients with Persistent Leukocytosis

Unexplained persistent leukocytosis in hospitalized patients often represents persistent inflammation-immunosuppression and catabolism syndrome (PICS) rather than active infection, particularly after major trauma, surgery, or cerebrovascular events. 7 These patients frequently develop eosinophilia (>500 cells/mm³) around hospital day 12 and may not benefit from additional antibiotics. 7