How should I manage asymptomatic leukocytosis in a 50‑year‑old woman?

Management of Asymptomatic Leukocytosis (WBC 15.6) in a 50-Year-Old Woman

In an asymptomatic 50-year-old woman with a WBC of 15.6, you should immediately obtain a complete blood count with manual differential to assess for left shift, immature cells, or blast forms, and systematically evaluate for occult infection, medication effects, and inflammatory conditions before considering hematologic malignancy. 1, 2

Immediate Diagnostic Steps

Order CBC with Manual Differential (Within 12-24 Hours)

• A manual differential is mandatory because automated analyzers miss critical findings such as band forms, immature granulocytes, blast cells, and toxic granulations 1, 2
• Assess the absolute neutrophil count and band count: an absolute band count ≥1,500 cells/mm³ has a likelihood ratio of 14.5 for bacterial infection, even in asymptomatic patients 1, 2
• Look specifically for:
  • Left shift (≥16% bands or absolute bands ≥1,500): likelihood ratio 4.7 for occult bacterial infection 1, 2
  • Neutrophil percentage >90%: likelihood ratio 7.5 for bacterial infection 1, 2
  • Blast cells: immediate hematology referral required 2, 3
  • Basophilia + eosinophilia + immature granulocytes: suggests chronic myeloid leukemia 2

Systematic Evaluation for Secondary Causes

Medication Review:

• Corticosteroids, lithium, and beta-agonists are the most common drug causes of leukocytosis 1, 4
• Lithium consistently causes leukocytosis; a WBC <4,000/mm³ would be unusual in lithium-treated patients 1

Occult Infection Assessment:

• Absence of fever does not exclude serious bacterial infection, particularly in middle-aged adults 2
• Evaluate for localizing symptoms: respiratory tract infection, urinary tract infection, skin/soft tissue infection 1
• Consider inflammatory markers (CRP, ESR) to assess for occult inflammatory processes 3

Physiological Stressors:

• Recent emotional stress, acute exercise, or physical trauma can double the WBC within hours due to catecholamine and cortisol release 1
• Smoking and obesity are chronic causes of mild leukocytosis 4

Chronic Inflammatory Conditions:

• Adult-onset Still's disease: 50% have WBC >15×10⁹/L with marked neutrophilia 1, 2
• Inflammatory bowel disease activity correlates with leukocytosis and thrombocytosis 1

Red Flags Requiring Urgent Hematology Referral

Immediate referral is indicated if:

• Blast cells present on peripheral smear (acute leukemia) 2, 3
• Basophilia + eosinophilia + left-shifted myeloid maturation (CML pattern) 2
• Splenomegaly or lymphadenopathy on physical examination 1, 2
• Constitutional symptoms: fever without infection, unintentional weight loss, night sweats, severe fatigue, bruising, or bleeding 4, 5
• Concurrent cytopenias: anemia or thrombocytopenia alongside leukocytosis 3, 6

Management Algorithm Based on Differential Results

If Manual Differential Shows Left Shift or High Neutrophil Percentage:

• Pursue infectious workup aggressively even if asymptomatic: urinalysis, chest imaging if respiratory symptoms, blood cultures if indicated 1, 2
• Do not assume absence of infection based on lack of symptoms 1

If Manual Differential is Normal (Mature Neutrophils, No Left Shift):

• Repeat CBC in 2-4 weeks to assess for persistence 4, 5
• Continue evaluation for medication effects and chronic inflammatory conditions 1
• Serial measurements are more informative than single values for unexplained persistent elevation 1

If Immature Cells or Dysplastic Features Present:

• Obtain comprehensive metabolic panel, LDH, uric acid to assess for tumor lysis risk 3
• Same-day hematology referral for bone marrow evaluation and cytogenetic testing 2, 3

Critical Pitfalls to Avoid

• Do not ignore a high neutrophil percentage (>84%) when total WBC is only mildly elevated: left shift can occur with normal or near-normal WBC and still indicate bacterial infection 1
• Do not treat with antibiotics based solely on leukocytosis without evidence of infection: asymptomatic mild elevations are often physiological 1
• Do not rely solely on automated analyzer results: manual smear review is essential to identify band forms and immature cells 1, 2
• Do not overlook transient causes: exercise, stress, and diurnal variations can cause mild elevations that resolve spontaneously 1
• Do not delay hematology referral if blast cells are suspected: acute leukemia requires urgent intervention 5, 6

Follow-Up Strategy

If initial workup is unrevealing and manual differential shows mature cells without left shift:

• Repeat CBC with manual differential in 2-4 weeks 4, 5
• If persistently elevated without explanation, consider hematology referral for further evaluation including bone marrow biopsy 4, 7
• Document any interval development of symptoms, organomegaly, or cytopenias 5, 6