What is primary neutrophilia?

Primary Neutrophilia: Definition and Clinical Significance

Primary neutrophilia is a pathological condition characterized by an abnormal increase in neutrophil count above 1,500 cells/μL due to intrinsic bone marrow disorders or genetic abnormalities, rather than as a response to external factors or underlying diseases.

Classification and Pathophysiology

Primary neutrophilia is distinguished from secondary neutrophilia based on the underlying cause:

• Primary neutrophilia: Results from intrinsic bone marrow disorders or genetic abnormalities that lead to autonomous overproduction of neutrophils

  • Often associated with myeloproliferative disorders
  • Involves dysregulation of neutrophil production, maturation, or release
  • Not a reactive response to infection, inflammation, or other external stimuli

• Secondary neutrophilia: Occurs as a physiological response to external factors such as:

  • Infections (bacterial, viral, fungal)
  • Inflammation
  • Medications
  • Stress
  • Malignancies

Diagnostic Criteria

Neutrophil count classification 1:

Grade	Neutrophil Count
Normal	≥1,500 cells/μL
Mild neutrophilia	1,500-2,000 cells/μL
Moderate neutrophilia	2,000-5,000 cells/μL
Severe neutrophilia	>5,000 cells/μL

Common Causes of Primary Neutrophilia

1. Myeloproliferative neoplasms:

   • Chronic myeloid leukemia (CML)
   • Polycythemia vera
   • Essential thrombocythemia
   • Primary myelofibrosis

2. Genetic disorders:

   • Hereditary neutrophilia
   • Specific genetic mutations affecting neutrophil production

3. Bone marrow disorders:

   • Myelodysplastic syndromes with increased neutrophil production
   • Certain forms of leukemia

Clinical Significance

The clinical significance of primary neutrophilia relates to:

1. Diagnostic value: May be the first indication of an underlying myeloproliferative disorder

2. Functional implications: Despite increased numbers, neutrophils in primary neutrophilia may have:

   • Altered function compared to normal neutrophils
   • Phenotypic heterogeneity and functional versatility 2
   • Potential for immune dysregulation

3. Disease progression marker: Persistent neutrophilia may indicate progression of the underlying myeloproliferative disorder

4. Treatment considerations: Management focuses on the underlying cause rather than the neutrophilia itself

Distinguishing Features from Secondary Neutrophilia

• Persistence: Primary neutrophilia tends to persist despite resolution of any acute conditions
• Associated findings: Often accompanied by other hematologic abnormalities
• Response to treatment: Does not normalize with treatment of infections or inflammatory conditions
• Bone marrow examination: Shows abnormal neutrophil production or maturation patterns

Management Approach

Management of primary neutrophilia focuses on:

1. Diagnosing the underlying cause:

   • Bone marrow aspiration and biopsy
   • Cytogenetic testing
   • Molecular studies for specific mutations

2. Treating the primary disorder:

   • Targeted therapies for specific myeloproliferative disorders
   • Supportive care
   • Monitoring for disease progression

3. Monitoring complications:

   • Thrombotic events
   • Disease transformation
   • Infection risk (paradoxically, some patients may still be susceptible)

Primary neutrophilia represents an important diagnostic entity that should prompt thorough investigation for underlying hematologic disorders, as early identification and management of these conditions can significantly impact patient outcomes.