How to approach a patient with leucocytosis (elevated white blood cell count)?

Approach to a Patient with Leukocytosis

A systematic diagnostic approach to leukocytosis should begin with a complete blood count with differential to characterize the type of elevated white blood cells, followed by targeted testing based on clinical presentation to identify the underlying cause, which is most commonly infection but may include inflammatory conditions, medication effects, or hematologic malignancies. 1

Initial Assessment

• Obtain a CBC with differential to identify which cell line is elevated and assess for left shift (increased band neutrophils) 1
• Review peripheral blood smear to examine morphology of white blood cells and rule out malignant cells 1
• Consider the following diagnostic thresholds:
  • WBC count >14,000 cells/mm³ has a likelihood ratio of 3.7 for bacterial infection 2
  • Elevated total band count (>1,500 cells/mm³) has the highest likelihood ratio (14.5) for bacterial infection 2
  • Increased percentage of neutrophils (>90%) and band neutrophils (>16%) have likelihood ratios of 7.5 and 4.7, respectively 2

Differential Diagnosis Based on Cell Type

Neutrophilic Leukocytosis

• Most common cause is infection (bacterial > viral) 3
• Non-infectious causes include:
  • Physical or emotional stress (seizures, anesthesia, overexertion) 3
  • Medications (corticosteroids, lithium, beta-agonists) 3
  • Inflammatory conditions 4
  • Smoking and obesity 4
  • Post-surgical state 5
  • Major trauma 5

Lymphocytic Leukocytosis

• Common in viral infections, especially in children 4
• Consider lymphoproliferative disorders if persistent 4
• Order flow cytometry if lymphoproliferative disorder is suspected based on morphology 1

Eosinophilic Leukocytosis

• Consider parasitic infections, allergic reactions, drug reactions 3
• May develop during prolonged hospitalization (seen in 15 of 29 patients with persistent unexplained leukocytosis in one study) 5

Basophilic Leukocytosis

• Rare, consider allergic reactions or myeloproliferative disorders 3

Focused Evaluation Based on Clinical Presentation

For Suspected Infection

• Urinalysis and urine culture if urinary symptoms are present or source is unclear 1
• Blood cultures if systemic symptoms or signs of sepsis are present 1
• Chest imaging if respiratory symptoms are present 1
• Consider CT imaging for suspected intra-abdominal infections 1
• Note that absence of fever does not exclude infection, particularly in older adults 2, 6

For Suspected Hematologic Malignancy

• Warning signs include:
  • Extremely elevated WBC counts (especially >100,000/mm³, which represents a medical emergency) 3
  • Concurrent abnormalities in red blood cell or platelet counts 3
  • Weight loss, bleeding, bruising, hepatosplenomegaly, lymphadenopathy 3
  • Immunosuppression 3
• Consider bone marrow examination and genetic analyses 7
• Referral to hematologist/oncologist if malignancy cannot be excluded 4

For Unexplained Persistent Leukocytosis

• Consider persistent inflammation-immunosuppression and catabolism syndrome (PICS), especially in patients with:
  • Major trauma 5
  • Prolonged hospitalization 5
  • Extensive tissue damage rather than active infection 5
• Monitor for development of opportunistic infections, including C. difficile 5
• Avoid unnecessary prolonged courses of broad-spectrum antibiotics 5

Management Algorithm

1. Determine severity of leukocytosis:

   • WBC >100,000/mm³: Medical emergency due to risk of brain infarction and hemorrhage 3
   • WBC 14,000-100,000/mm³: Requires evaluation but less urgent 2

2. Evaluate for infection:

   • If infection is suspected despite negative initial tests, consider occult infection sites 6
   • For suspected occult bacterial infection with appropriate clinical presentation, consider empiric antimicrobial therapy based on the most likely source 6
   • Limit antibiotic duration if source control is adequate 6

3. If infection is ruled out, consider:

   • Medication review and possible discontinuation of causative agents 3
   • Evaluation for inflammatory conditions 4
   • Hematology consultation if persistent or if concerning features for malignancy 4

4. Monitor response:

   • Serial WBC counts to track response to therapy 6
   • If leukocytosis persists despite treatment of apparent cause, broaden differential diagnosis 5

Common Pitfalls to Avoid

• Treating asymptomatic patients with antibiotics based solely on mildly elevated WBC counts 6
• Overlooking the significance of absolute neutrophil count elevation when total WBC count is only mildly elevated 1
• Missing hematologic malignancies by failing to evaluate patients with concurrent abnormalities in other cell lines 3
• Prolonged empiric antibiotic use for unexplained leukocytosis without evidence of infection 5