What labs should be ordered to evaluate a patient with leukocytosis (elevated White Blood Cell count)?

Laboratory Evaluation for Leukocytosis

When evaluating a patient with leukocytosis (elevated white blood cell count), a complete blood count with differential, inflammatory markers, and appropriate cultures should be performed, with additional specialized testing based on suspected etiology. 1, 2

Initial Laboratory Evaluation

Core Laboratory Tests

• Complete Blood Count (CBC) with differential 1, 2

  • Manual differential preferred to assess bands and immature forms
  • Evaluate for left shift (bands >16% or band count >1,500 cells/mm³)
  • Note: WBC count >14,000 cells/mm³ has a likelihood ratio of 3.7 for bacterial infection

• Inflammatory markers 1, 2

  • C-reactive protein (CRP)
  • Erythrocyte sedimentation rate (ESR)
  • Procalcitonin (more specific for bacterial infection)

• Basic metabolic panel 1, 2

  • Electrolytes
  • Renal function
  • Liver enzymes

• Peripheral blood smear examination 2, 3

  • Critical for distinguishing reactive from malignant causes
  • Assess cell morphology, maturity, and presence of dysplasia
  • Look for toxic granulations suggesting infection

Additional Testing Based on Clinical Suspicion

For Suspected Infection

• Blood cultures 2
• Urine culture (if urinary symptoms) 1
• Stool cultures and C. difficile testing (if gastrointestinal symptoms) 1
• Respiratory cultures (if respiratory symptoms) 2

For Suspected Hematologic Malignancy

• Bone marrow aspiration and biopsy 1, 2

  • Morphologic examination
  • Cytochemistry
  • Immunophenotyping by flow cytometry
  • Cytogenetic analysis

• Molecular genetic studies 1, 2

  • For acute leukemia: FLT3-ITD, BCR-ABL1, etc.
  • For B-ALL: t(9;22), KMT2A translocations
  • Can be performed on peripheral blood, bone marrow, or tissue samples

• Cerebrospinal fluid analysis (if neurological symptoms or ALL) 1

  • Cell count
  • Cytology with blast enumeration
  • Flow cytometry

Specialized Testing Based on Differential

For Neutrophilic Leukocytosis

• Neutrophil-to-lymphocyte ratio (NLR) 2
  • Values >3.0 suggest inflammation or infection

For Eosinophilia or Basophilia

• Allergy testing 4
• Parasite screening 4, 5

For Lymphocytosis

• Flow cytometry of peripheral blood 1, 2, 3
  • To assess clonality and characterize lymphoid populations
• Viral studies (EBV, CMV, HIV) 5, 6

For Monocytosis

• Molecular testing for BCR-ABL1 (to rule out chronic myeloid leukemia) 1, 2

Important Considerations

• Critical values requiring urgent action:

  • WBC count >100,000/mm³ represents a medical emergency due to risk of leukostasis 4, 3
  • Presence of blasts in peripheral blood 1, 3

• Common pitfalls to avoid:

  • Attributing leukocytosis solely to stress without excluding infection 2
  • Failing to examine peripheral blood smear in cases of unexplained leukocytosis 2, 3
  • Not considering medication-induced leukocytosis (corticosteroids, lithium, beta-agonists) 4, 5

• Monitor trends in cell counts rather than relying on a single measurement 2

• Consider pregnancy-specific and age-specific normal ranges when interpreting results 5

By following this structured approach to laboratory evaluation of leukocytosis, clinicians can efficiently distinguish between benign reactive causes and more serious conditions requiring specialist referral.