What are the normal white blood cell count and differential percentages, and how should leukocytosis or leukopenia be evaluated?

Normal White Blood Cell Count and Differential

Normal white blood cell count ranges from 4,000-10,000 cells/mm³, with neutrophils comprising 40-70%, lymphocytes 20-40%, monocytes 2-8%, eosinophils 1-4%, and basophils 0-1%. 1

Evaluation of Leukocytosis

Initial Laboratory Assessment

Immediately obtain a manual differential count—automated analyzers are insufficient for detecting critical findings like band forms and left shift. 2, 3

• Calculate the absolute band count by multiplying total WBC by band percentage: an absolute band count ≥1,500 cells/mm³ has the highest likelihood ratio (14.5) for documented bacterial infection 2
• Assess band percentage: ≥16% represents a left shift with likelihood ratio of 4.7 for bacterial infection, even when total WBC is normal 2
• Neutrophil percentage >90% has a likelihood ratio of 7.5 for bacterial infection 2
• Total WBC ≥14,000 cells/mm³ alone has only a likelihood ratio of 3.7, making the differential more important than the total count 2

Systematic Diagnostic Algorithm

Step 1: Confirm the leukocytosis and examine peripheral blood smear 4, 5

• Review smear for toxic granulations, immature cells (blasts), dysplasia, and uniformity of white blood cells 4, 5
• Distinguish myeloid versus lymphoid process based on cell morphology 5

Step 2: Assess for infection-related causes 2, 4

• Evaluate for fever, localizing symptoms, or signs of sepsis requiring bacterial infection workup 2
• Respiratory tract infections, urinary tract infections, skin/soft tissue infections, and gastrointestinal infections commonly cause leukocytosis 2
• Critical pitfall: Do not ignore left shift when total WBC is only mildly elevated—left shift is more predictive than total WBC count 2, 3

Step 3: Review medications and physiological causes 2, 6

• Corticosteroids, lithium (consistently causes leukocytosis; WBC <4,000/mm³ would be unusual), and beta-agonists are the most common medication causes 2, 6
• Emotional stress triggers leukocytosis through catecholamines and cortisol release 2
• Acute exercise causes immediate WBC elevation, particularly granulocytes and NK cells 2
• Physical stress from surgery, trauma, or seizures can double peripheral WBC within hours due to large bone marrow storage pools 4, 6

Step 4: Identify red flags requiring hematology referral 2, 6, 5

• Extreme leukocytosis (>100,000/mm³) represents a medical emergency due to risk of cerebral infarction and hemorrhage requiring immediate cytoreductive therapy 2, 6
• Splenomegaly and lymphadenopathy suggest malignancy 2
• Constitutional symptoms: fever, weight loss, bruising, or fatigue 4, 6
• Concurrent abnormalities in red blood cells or platelets 6
• Presence of blasts or blast equivalents on peripheral smear 5

Specific Differential Patterns

Neutrophilic leukocytosis 2, 7

• Most commonly indicates bacterial infection when accompanied by left shift 2
• Adult-onset Still's disease: 50% have WBC >15×10⁹/L; 37% have >20×10⁹/L with marked neutrophilia 2
• Deep eosinopenia (<50 cells/mm³) with neutrophilia has 94% specificity for bacterial infection, particularly urinary and biliary tract infections 7

Lymphocytosis 4, 5

• Childhood viral illnesses commonly present with lymphocytosis 4
• Pleomorphic lymphocytes suggest reactive process; monomorphic population favors lymphoproliferative neoplasm requiring flow cytometry 5

Eosinophilia 4, 6

• Parasitic infections, allergic reactions, and various inflammatory conditions 4, 6

Evaluation of Leukopenia

Leukopenia (WBC <4,000/mm³) requires assessment for infection, medications, autoimmune conditions, and primary bone marrow disorders. 1

• Critical pitfall: Normal or low WBC does not exclude bacterial infection—sensitivity is low, particularly in elderly or immunosuppressed patients 2
• Bacterial infections can present with leukopenia, particularly in early stages or severe disease 2

Key Diagnostic Considerations

• Obtain manual differential to assess absolute neutrophil count (neutropenia defined as <1,500 cells/mm³) 1
• Review medications causing leukopenia: chemotherapy, immunosuppressants, certain antibiotics 1
• Evaluate for autoimmune conditions and viral infections 1
• If persistent or severe (<1,000 cells/mm³), refer to hematology for bone marrow evaluation 1

Critical Pitfalls to Avoid

• Do not overinterpret single mild elevations without clinical context—transient elevations occur with exercise, stress, or diurnal variations 2
• Do not rely on automated differential alone—manual differential is essential to accurately assess band forms 2, 3
• Do not obtain urinalysis or urine culture in truly asymptomatic patients, even with leukocytosis—bacteriuria prevalence is 15-50% in elderly non-catheterized patients and does not indicate infection 3
• Do not treat asymptomatic patients with antibiotics based solely on mildly elevated neutrophil counts 2
• Do not ignore elevated band counts when total WBC is only mildly elevated—left shift can occur with normal total WBC and still indicate serious bacterial infection 2, 3
• Serial measurements are more informative than single values for unexplained persistent elevation 2