What causes a high white blood cell (WBC) count?

Causes of High White Blood Cell Count

High WBC count is most commonly caused by bacterial infection, but also results from physiological stress, medications (especially corticosteroids and lithium), smoking, obesity, chronic inflammation, and less commonly, hematologic malignancies. 1, 2, 3

Infectious Causes (Most Common)

Bacterial infections are the leading cause of leukocytosis and should be your first consideration. 1

Key Diagnostic Markers for Bacterial Infection:

• Absolute band neutrophil count ≥1,500 cells/mm³ has the highest diagnostic value (likelihood ratio 14.5) 1
• Neutrophil percentage >90% carries a likelihood ratio of 7.5 for bacterial infection 1
• Left shift (≥16% band neutrophils) has a likelihood ratio of 4.7, even with normal total WBC 1
• Total WBC ≥14,000 cells/mm³ warrants careful assessment for bacterial infection, even without fever 1, 2

Common Bacterial Sources:

• Respiratory tract infections 1
• Urinary tract infections 1
• Skin and soft tissue infections 1
• Gastrointestinal infections 1
• Spontaneous bacterial peritonitis (in cirrhosis patients with ascites) 1

Viral Infections:

• Generally cause lower WBC counts or normal counts with lymphocyte predominance 4
• Influenza specifically causes leukopenia in 8-27% of cases 2

Physiological and Stress-Related Causes

Physical and emotional stress can double the WBC count within hours due to mobilization from bone marrow storage pools. 3, 5

Acute Stressors:

• Surgery 3, 5
• Exercise (particularly intense or prolonged) 2, 3
• Trauma 3, 5
• Emotional stress 2, 3
• Seizures 5

Medication-Induced Leukocytosis

Common Culprits:

• Corticosteroids (most common medication cause) 2, 3, 5
• Lithium (consistently causes leukocytosis; WBC <4,000/mm³ would be unusual in lithium-treated patients) 1, 2, 3
• Beta-agonists 1, 5
• Epinephrine 1

Chronic Non-Infectious Causes

Lifestyle and Metabolic Factors:

• Smoking 2, 3
• Obesity (associated with higher baseline WBC) 2, 3, 6
• Chronic inflammatory conditions including inflammatory bowel disease 2, 3

Medical Conditions:

• Asplenia 3
• Chronic kidney disease 6
• Chronic obstructive pulmonary disease 6
• Congestive heart failure (actually associated with lower WBC) 6
• Diabetes mellitus 6

Hematologic Malignancies (Less Common but Serious)

Suspect malignancy when WBC is extremely elevated (>100,000/mm³) or accompanied by other cytopenias. 3, 5

Red Flags for Malignancy:

• Fever with weight loss 3
• Unexplained bruising or bleeding 3
• Fatigue 3
• Hepatosplenomegaly or lymphadenopathy 5
• Concurrent anemia or thrombocytopenia 5
• Immunosuppression 5

Types:

• Acute leukemias (patients typically ill at presentation) 7, 5
• Chronic leukemias (often diagnosed incidentally) 5
• Myeloproliferative disorders 5

WBC >100,000/mm³ represents a medical emergency due to risk of brain infarction and hemorrhage. 5

Diagnostic Approach Algorithm

Step 1: Obtain Complete Blood Count with Manual Differential

• Manual differential is superior to automated for assessing bands and immature forms 1
• Calculate absolute neutrophil count and absolute band count 1, 2

Step 2: Assess Clinical Context

• Fever, localizing symptoms, or signs of sepsis mandate evaluation for bacterial infection 2
• Review medication list (corticosteroids, lithium, beta-agonists) 1, 2
• Consider recent physical/emotional stress or exercise 2, 3

Step 3: Risk Stratify Based on WBC Pattern

• WBC ≥14,000 with left shift: High suspicion for bacterial infection—obtain blood cultures, site-specific cultures, imaging as indicated 1, 2
• WBC 11,000-14,500 without left shift: May be normal for hospitalized patients with comorbidities; interpret cautiously 6
• WBC >100,000: Medical emergency; immediate hematology consultation 5

Step 4: Additional Testing When Indicated

• Blood cultures if systemic infection suspected 1
• Urinalysis with culture for urinary symptoms 1
• Chest imaging for respiratory symptoms 1
• Paracentesis if cirrhosis with ascites (neutrophil count >250 cells/mm³ in ascitic fluid indicates spontaneous bacterial peritonitis) 1
• C-reactive protein for inflammatory conditions 2

Critical Pitfalls to Avoid

• Do not dismiss WBC 11,000-14,500 as automatically abnormal in hospitalized patients—13.5% of hospitalized patients without infection have WBC in this range 6
• Normal WBC does not exclude bacterial infection, especially in elderly or immunosuppressed patients 2
• Left shift can occur with normal total WBC and still indicates bacterial infection 1
• Do not over-interpret a single mildly elevated WBC without clinical context—transient elevations occur with diurnal variation 2
• Serial measurements are more informative than single values for persistent unexplained elevation 2
• High WBC and granulocyte counts are clear evidence of bacterial etiology, but low or normal values do not rule it out 4

Special Populations

Age-Related Considerations:

• Use age-specific reference ranges 2, 3
• Mean WBC decreases with age 6

Race:

• Black patients have lower baseline WBC compared to White patients 6

Pregnancy:

• Use pregnancy-specific normal ranges 3