What are the causes of leukocytosis (elevated white blood cell count)?

Etiology of Leukocytosis

Leukocytosis is most commonly caused by infections and inflammatory processes, but can also result from physical or emotional stress, medications, and primary bone marrow disorders including malignancies. 1

Physiologic and Benign Causes

Infections

• Bacterial infections - often cause neutrophilia with left shift (increased band forms)

  • WBC >14,000 cells/mm³ (LR 3.7 for bacterial infection)
  • Band counts >1,500 cells/mm³ (LR 14.5)
  • Neutrophils >90% (LR 7.5)
  • Band neutrophils >16% (LR 4.7) 2

• Viral infections - typically cause lymphocytosis, especially in children 2

• Parasitic infections - often associated with eosinophilia 2

Stress Response

• Physical stress (seizures, anesthesia, overexertion)
• Emotional stress
• Intense exercise 2, 1

Medications

• Corticosteroids
• Lithium
• Beta-agonists
• Epinephrine 2, 1

Inflammatory Conditions

• Chronic inflammatory disorders
• Tissue damage/injury
• Autoimmune diseases 2

Pathologic Causes

Primary Bone Marrow Disorders

• Acute leukemias - patients often ill at presentation
• Chronic leukemias - often diagnosed incidentally
  • Chronic myeloid leukemia (CML)
• Myeloproliferative disorders 1

Malignancies

• Solid tumors can cause leukocytosis through:
  • Bone marrow metastases
  • Paraneoplastic syndrome (cytokine production)
  • Particularly aggressive cancers like anaplastic thyroid carcinoma 3

Other Causes

• Persistent inflammation-immunosuppression and catabolism syndrome (PICS)
  • Seen in prolonged hospitalization after major trauma, surgery, or sepsis 4
• Splenectomy or hyposplenism
• Hemolysis

Red Flags for Serious Causes

• Extremely elevated WBC counts (>100,000/mm³) - medical emergency due to risk of brain infarction and hemorrhage 1
• Concurrent abnormalities in red blood cell or platelet counts
• Constitutional symptoms (weight loss, night sweats, fever)
• Bleeding or bruising
• Hepatosplenomegaly or lymphadenopathy
• Immunosuppression 1

Diagnostic Approach

1. Review complete blood count with differential

   • Neutrophilia suggests bacterial infection or inflammation
   • Lymphocytosis suggests viral infection or lymphoproliferative disorder
   • Eosinophilia suggests parasitic infection, allergic reaction, or certain malignancies
   • Monocytosis suggests chronic infection, inflammatory disease, or monocytic leukemia

2. Evaluate peripheral blood smear for:

   • Left shift (increased band forms)
   • Blasts or immature cells (suggesting leukemia)
   • Abnormal cell morphology

3. Consider inflammatory markers:

   • C-reactive protein (CRP)
   • Procalcitonin (PCT) - better correlation with sepsis severity 2
   • Calculate neutrophil-to-lymphocyte ratio as marker of inflammation severity 2

4. Further testing based on clinical suspicion:

   • Blood cultures if infection suspected
   • Bone marrow aspiration/biopsy if primary hematologic disorder suspected
   • Imaging studies as indicated by symptoms

Remember that WBC counts above 100,000/mm³ represent a medical emergency requiring immediate intervention due to the risk of brain infarction and hemorrhage 1.