How should I manage an asymptomatic 39-year-old woman with no known comorbidities who has neutrophil-predominant leukocytosis (white blood cell count 14.8 ×10⁹/L)?

Management of Asymptomatic Neutrophilic Leukocytosis in a 39-Year-Old Woman

In an asymptomatic 39-year-old woman with a WBC of 14.8 × 10⁹/L and neutrophilic predominance, the appropriate initial approach is to repeat the complete blood count with manual differential and obtain a peripheral blood smear to assess for left shift, immature forms, dysplasia, or blast cells, while simultaneously evaluating for common physiologic and reactive causes before considering hematologic malignancy. 1, 2

Initial Risk Stratification

The WBC count of 14.8 × 10⁹/L falls into a moderate elevation range that warrants evaluation but does not constitute a medical emergency. 1 A WBC >100,000/μL would represent a true emergency requiring immediate intervention with aggressive hydration and cytoreduction, but this patient's count is well below that threshold. 1, 3

Key Diagnostic Features to Assess

The peripheral blood smear is essential to distinguish benign from malignant leukocytosis. 4 Specifically evaluate for:

• Left shift ≥16% band neutrophils (likelihood ratio 4.7 for bacterial infection) 1
• Absolute band count ≥1,500 cells/mm³ (likelihood ratio 14.5 for bacterial infection) 1
• Neutrophil percentage >90% (likelihood ratio 7.5 for bacterial infection) 1
• Presence of blast cells, immature myeloid forms, or dysplastic features (requires immediate hematology referral regardless of total WBC) 1
• Toxic granulations or activated neutrophil changes (suggests reactive process, commonly infection) 4

Evaluation for Reactive Causes

Since the patient is asymptomatic, systematically exclude common nonmalignant etiologies before pursuing malignancy workup. 2

Physiologic Stressors

• Recent surgery, exercise, trauma, or emotional stress can double the peripheral WBC count within hours due to demargination from bone marrow storage pools 2
• Smoking status (chronic smoking causes persistent leukocytosis) 2
• Obesity (associated with chronic low-grade inflammation and leukocytosis) 2

Medication Review

Certain medications can cause leukocytosis, including corticosteroids, lithium, beta-agonists, and colony-stimulating factors. 2

Occult Infection

Even in asymptomatic patients, evaluate for:

• Subclinical infections that may not produce overt symptoms 2
• Chronic inflammatory conditions (inflammatory bowel disease, rheumatologic disorders) 2
• Asplenia or functional hyposplenism (causes persistent leukocytosis) 2

Important caveat: Do NOT pursue urinalysis or urine culture in this asymptomatic patient, as pyuria without symptoms does not indicate infection requiring treatment and contributes to unnecessary antibiotic use. 5

When to Refer to Hematology

Immediate hematology referral is indicated if: 1, 2

• Peripheral smear shows blast cells, immature forms, or dysplastic features
• Splenomegaly or lymphadenopathy on physical examination
• Constitutional symptoms develop (fever, weight loss, bruising, fatigue)
• Persistent leukocytosis without identifiable reactive cause after repeat testing

Follow-Up Strategy

If the initial peripheral smear shows only mature neutrophils without left shift, blasts, or dysplasia, and no reactive cause is immediately identified:

• Repeat CBC with differential in 2-4 weeks to determine if leukocytosis is persistent or transient 2, 6
• Clinical monitoring for development of symptoms, splenomegaly, or lymphadenopathy 2
• Avoid repeated testing at short intervals unless clinical course changes, as this does not affect decision-making 6

Persistent Leukocytosis Without Cause

If leukocytosis persists beyond 4-6 weeks without identified reactive etiology and remains asymptomatic, hematology referral is warranted to exclude chronic myeloproliferative neoplasms (such as chronic myeloid leukemia, polycythemia vera, or essential thrombocythemia), even in the absence of overt symptoms. 2, 7

Critical distinction: In chronic myeloid leukemia, leukostatic symptoms are uncommon even with WBC >100,000/μL in chronic phase, so absence of symptoms does not exclude malignancy. 1 However, at a WBC of 14.8 × 10⁹/L, CML would typically present with additional features such as basophilia, eosinophilia, or splenomegaly. 8

What NOT to Do

• Do not obtain blood cultures in an afebrile, asymptomatic patient without clinical suspicion for infection 3
• Do not initiate empiric antibiotics based solely on leukocytosis without evidence of infection 9
• Do not perform bone marrow examination until peripheral smear evaluation and hematology consultation are completed 4
• Do not order extensive autoimmune or inflammatory workup without clinical features suggesting these conditions 2