What causes an elevated White Blood Cell (WBC) count?

Causes of Elevated White Blood Cell Count (Leukocytosis)

An elevated white blood cell (WBC) count is most commonly caused by infections (particularly bacterial), inflammatory conditions, medications (especially corticosteroids), and hematologic malignancies, with the specific cause best determined by evaluating the WBC differential, associated symptoms, and clinical context. 1, 2

Infectious Causes

• Bacterial infections: Most common infectious cause of significant leukocytosis

  • Often produces neutrophilia with left shift (increased band forms)
  • WBC count >14,000 cells/mm³ has a likelihood ratio of 3.7 for bacterial infection 1
  • Elevated total band count (>1,500 cells/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 1

• Viral infections:

  • Typically cause lymphocytosis, especially in children 3
  • Usually produce less dramatic WBC elevation than bacterial infections
  • Specific viral patterns: monocytosis may suggest intracellular pathogens 1

• Parasitic infections:

  • Often associated with eosinophilia 1, 2

Inflammatory/Autoimmune Causes

• Rheumatoid arthritis:

  • Up to 27% of patients have leukocytosis 4
  • Higher prevalence (40%) in patients on corticosteroid therapy 4
  • More common with active disease 4

• Other inflammatory conditions:

  • Vasculitis
  • Inflammatory bowel disease
  • Tissue injury/necrosis
  • Pericarditis 1

Medication-Induced Causes

• Corticosteroids:

  • Dose-dependent effect
  • Mean WBC increase of 4.84 × 10⁹/L within 48 hours after high-dose steroids 5
  • Medium doses: mean increase of 1.7 × 10⁹/L 5
  • Low doses: mean increase of 0.3 × 10⁹/L 5

• Other medications:

  • Lithium
  • Beta-agonists
  • Epinephrine 2, 6

Physiologic/Stress Responses

• Physical stress:

  • Surgery
  • Exercise (especially intense endurance exercise) 1
  • Trauma
  • Seizures 2, 6

• Emotional stress 2, 6

Primary Bone Marrow Disorders

• Acute leukemias:

  • Often present with extremely elevated WBC counts
  • Usually accompanied by symptoms (fever, weight loss, bruising, fatigue)
  • May have concurrent abnormalities in RBC or platelet counts 2, 6

• Chronic leukemias:

  • Often diagnosed incidentally
  • Chronic myeloid leukemia (CML) may present with very high WBC counts 7

• Myeloproliferative disorders:

  • Polycythemia vera
  • Essential thrombocythemia
  • Primary myelofibrosis 6

Other Causes

• Asplenia: Absence or dysfunction of spleen 2

• Smoking: Can cause chronic elevation in WBC count 2

• Obesity: Associated with mild chronic leukocytosis 2

Clinical Pearls and Pitfalls

• Medical emergency: WBC counts >100,000/mm³ represent a medical emergency due to risk of brain infarction and hemorrhage 6

• Differential diagnosis: When evaluating leukocytosis, consider:

  • Magnitude of elevation
  • Cell types involved (neutrophils, lymphocytes, eosinophils, etc.)
  • Presence of immature forms
  • Associated symptoms
  • Recent medication changes

• Steroid-induced leukocytosis: Increases >4.84 × 10⁹/L after high-dose steroids or any increase after low-dose steroids should prompt investigation for other causes 5

• Infection vs. inflammation: Bacterial infections typically cause more pronounced leukocytosis than viral infections, but normal WBC counts do not rule out bacterial infection 3

• Malignancy red flags: Suspect primary bone marrow disorders with extremely elevated WBC counts, concurrent abnormalities in RBC or platelet counts, weight loss, bleeding/bruising, hepatosplenomegaly, or lymphadenopathy 2, 6