What is the initial workup for leukocytosis (elevated white blood cell count)?

Initial Laboratory Workup for Leukocytosis

The essential first step in evaluating leukocytosis is a complete blood count (CBC) with differential to characterize which cell line is elevated, followed by peripheral blood smear review to examine morphology and assess for left shift or malignant cells. 1

Initial Diagnostic Steps

• Complete blood count (CBC) with differential is the cornerstone of initial evaluation to identify which white blood cell line is elevated 1
• Peripheral blood smear review is essential to examine morphology of white blood cells, assess for left shift (increased band neutrophils), and rule out malignant cells 1
• A comprehensive metabolic panel should be obtained to monitor for potential tumor lysis syndrome and assess organ function 1

Evaluation Based on Cell Type Predominance

Neutrophilic Leukocytosis

• An elevated total band count (>1500/mm³) has the highest likelihood ratio (14.5) for detecting bacterial infection 1, 2
• Increased percentage of neutrophils (>90%) and band neutrophils (>16%) have likelihood ratios of 7.5 and 4.7, respectively, for bacterial infection 1, 2
• A WBC count >14,000 cells/mm³ has a likelihood ratio of 3.7 for bacterial infection 1
• Evaluate for common infectious causes including respiratory, urinary tract, skin/soft tissue, and gastrointestinal infections 2

Lymphocytic Leukocytosis

• Flow cytometry should be considered if lymphoproliferative disorder is suspected based on morphology 1
• Assess for viral infections which commonly cause lymphocytosis 3

Severe Leukocytosis (Hyperleukocytosis >100,000/μL)

• Blood cultures should be obtained before starting antibiotics if infection is suspected 4
• Consider hematology consultation for urgent evaluation of possible leukemia 3
• Monitor for and prevent tumor lysis syndrome with appropriate hydration and possibly allopurinol or rasburicase 4

Site-Specific Evaluation

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

Differential Diagnosis Considerations

• Infections and chronic inflammatory conditions are common causes of secondary leukocytosis 3
• Medications that can cause neutrophilia include lithium, beta-agonists, and epinephrine 2
• Constitutional symptoms along with an abnormal peripheral blood smear result indicate the need for evaluation for malignancy 3
• Persistent neutrophilic leukocytosis above 50,000 cells/μL when the cause is other than leukemia defines a leukemoid reaction 5

Common Pitfalls to Avoid

• Overlooking the significance of absolute neutrophil count elevation when total WBC count is only mildly elevated 1, 2
• Treating asymptomatic patients with antibiotics based solely on mildly elevated WBC counts 1
• Failing to recognize that leukocytosis without fever does not exclude infection, particularly in older adults 1
• Overlooking non-infectious causes of leukocytosis such as malignancies, hemorrhage, or hemolysis 5
• Failing to distinguish between reactive lymphoid proliferation and lymphoproliferative disorders by examining lymphocyte morphology 6

Special Considerations

• In patients with unexplained persistent leukocytosis despite antibiotic therapy, consider non-infectious causes such as tissue damage rather than active infection 7
• Urgent referral to a hematology subspecialist is indicated in cases of suspected acute leukemia 3