What is leukocytosis (elevated white blood cell count)?

Definition of Leukocytosis

Leukocytosis is defined as an elevated white blood cell (WBC) count above the normal reference range, typically greater than 11,000 cells/mm³ in nonpregnant adults. 1, 2

Normal Ranges and Classification

• Normal WBC count range: 4,000-11,000 cells/mm³ for adults
• Age-specific and pregnancy-specific normal ranges should be considered
• Severity classification:
  • Mild: 11,000-15,000 cells/mm³
  • Moderate: 15,000-30,000 cells/mm³
  • Severe: >30,000 cells/mm³
  • Critical: >100,000 cells/mm³ (medical emergency due to risk of brain infarction and hemorrhage) 3

Pathophysiology

Leukocytosis occurs through several mechanisms:

• Increased production and release of white blood cells from bone marrow
• Demargination of white blood cells from the vascular endothelium
• Decreased extravasation of white blood cells into tissues
• Decreased apoptosis of circulating white blood cells

Types of Leukocytosis (Based on Differential Count)

1. Neutrophilia: Elevated neutrophil count

   • Most common type of leukocytosis
   • Often indicates bacterial infection or inflammation
   • Left shift: increased percentage of band (immature) neutrophils (>6%) or elevated absolute band count (>1,500 cells/mm³) 1

2. Lymphocytosis: Elevated lymphocyte count

   • Common in viral infections, especially in children
   • Can be seen in certain lymphoid malignancies

3. Monocytosis: Elevated monocyte count

   • Seen in chronic infections, inflammatory conditions
   • Can be associated with monocytic leukemias

4. Eosinophilia: Elevated eosinophil count

   • Allergic reactions, parasitic infections
   • Certain hematologic malignancies

5. Basophilia: Elevated basophil count

   • Rare, can be seen in myeloproliferative disorders
   • Allergic reactions, inflammatory conditions

Common Causes of Leukocytosis

Non-Malignant Causes

1. Infections

   • Bacterial infections (most common cause)
   • Viral infections (often with lymphocytosis rather than neutrophilia)
   • Fungal and parasitic infections

2. Inflammatory Conditions

   • Autoimmune disorders
   • Tissue damage/necrosis
   • Post-surgical states

3. Physiologic Stress

   • Physical stress (seizures, exercise, anesthesia)
   • Emotional stress
   • Pregnancy and labor

4. Medications

   • Corticosteroids
   • Lithium
   • Beta-agonists
   • G-CSF (filgrastim)
   • Epinephrine

5. Other Conditions

   • Smoking
   • Obesity
   • Asplenia
   • Tissue injury/trauma
   • Burns

Malignant Causes

1. Acute Leukemias

   • Acute myeloid leukemia (AML)
   • Acute lymphoblastic leukemia (ALL)
   • Often present with severe symptoms and critical leukocytosis

2. Chronic Leukemias

   • Chronic myeloid leukemia (CML)
   • Chronic lymphocytic leukemia (CLL)
   • Often diagnosed incidentally with less severe symptoms

3. Myeloproliferative Disorders

   • Polycythemia vera
   • Essential thrombocythemia
   • Primary myelofibrosis

Clinical Significance

• WBC count >14,000 cells/mm³ has a likelihood ratio of 3.7 for bacterial infection 1
• WBC count >100,000 cells/mm³ constitutes a medical emergency (hyperleukocytosis) due to risk of:
  • Leukostasis (sludging of WBCs in microvasculature)
  • Brain infarction or hemorrhage
  • Pulmonary infiltrates
  • Tumor lysis syndrome 4, 5

Diagnostic Approach

When leukocytosis is identified:

1. Evaluate the complete blood count with differential
2. Examine peripheral blood smear for cell morphology and maturity
3. Assess for concurrent abnormalities in red blood cells or platelets
4. Look for clinical signs of infection or inflammation
5. Consider bone marrow disorders if extremely elevated counts or abnormalities in other cell lines

Red Flags for Malignancy

• Extremely elevated WBC count (>50,000 cells/mm³)
• Abnormalities in other blood cell lines (anemia, thrombocytopenia)
• Constitutional symptoms (fever, weight loss, night sweats)
• Hepatosplenomegaly or lymphadenopathy
• Unusual or immature cells on peripheral smear
• Persistent unexplained leukocytosis

Leukocytosis is a common laboratory finding that requires careful evaluation to determine its cause and clinical significance. While most cases are due to benign, reactive processes, it can occasionally be the first sign of a serious hematologic malignancy.