What is the initial lab workup for a patient presenting with leukocytosis (elevated white blood cell count)?

Initial Laboratory Workup for Leukocytosis

The initial laboratory workup for a patient with leukocytosis should include a complete blood count with differential, peripheral blood smear review, comprehensive metabolic panel, and targeted diagnostic tests based on suspected underlying causes. 1, 2

Initial Assessment

• Complete blood count (CBC) with differential is the first essential test to characterize the leukocytosis and identify which cell line is elevated 1, 2
• Peripheral blood smear review to examine morphology of white blood cells, assess for left shift (increased band neutrophils), and rule out malignant cells 1, 2
• Comprehensive metabolic panel to monitor for potential tumor lysis syndrome and assess organ function 1

Differential Diagnosis Based on Cell Type

Neutrophilic Leukocytosis

• Evaluate for left shift - an elevated total band count (>1500/mm³) has the highest likelihood ratio (14.5) for detecting bacterial infection 1
• Increased percentage of neutrophils (>90%) and band neutrophils (>16%) have likelihood ratios of 7.5 and 4.7, respectively, for bacterial infection 1, 3
• WBC count >14,000 cells/mm³ has a likelihood ratio of 3.7 for bacterial infection 1, 2

Lymphocytic Leukocytosis

• Flow cytometry should be considered if lymphoproliferative disorder is suspected based on morphology 1, 4
• Viral studies may be warranted, particularly in children with lymphocytosis 5

Site-Specific Evaluation

• Urinalysis and urine culture if urinary symptoms are present or if source of infection is unclear 1, 3
• Blood cultures if systemic symptoms or signs of sepsis are present 3
• Respiratory evaluation (including chest imaging) if respiratory symptoms are present 3
• Consider CT imaging for suspected intra-abdominal infections 3

Special Considerations

• Leukocytosis without fever does not exclude infection, particularly in older adults 1, 2
• Non-infectious causes of leukocytosis include stress (surgery, trauma, exercise), medications, smoking, obesity, and chronic inflammatory conditions 5, 6
• Constitutional symptoms (fever, weight loss, bruising, fatigue) along with abnormal peripheral blood smear should prompt evaluation for hematologic malignancy 6, 4

Common Pitfalls

• Treating asymptomatic patients with antibiotics based solely on mildly elevated WBC counts can lead to unnecessary antibiotic use 2, 3
• Overlooking the significance of absolute neutrophil count elevation when total WBC count is only mildly elevated 2
• Failing to consider non-infectious causes of persistent leukocytosis, leading to prolonged unnecessary antibiotic therapy 7
• Not recognizing that the peripheral WBC count can double within hours after certain stimuli due to bone marrow storage and marginated pools of neutrophils 5

When to Consider Hematology Referral

• Persistent unexplained leukocytosis despite negative infection workup 4, 7
• Abnormal peripheral blood smear suggesting hematologic malignancy 6, 4
• Urgent referral to hematology is indicated in cases of suspected acute leukemia 6