What is the clinical significance of elevated neutrophils (neutrophilia)?

Clinical Significance of Elevated Neutrophils (Neutrophilia)

Elevated neutrophils (neutrophilia) primarily indicates an ongoing infection, inflammatory process, or potential hematologic disorder that requires prompt evaluation to identify the underlying cause and initiate appropriate treatment.

Definition and Diagnostic Criteria

Neutrophilia is defined by the following criteria:

• Total white blood cell (WBC) count >14,000 cells/mm³
• Neutrophil percentage >90%
• Elevated total band count >1,500 cells/mm³
• Increased percentage of band neutrophils >16% 1, 2

Major Clinical Significance

1. Bacterial Infections

• Neutrophilia has a high likelihood ratio (3.7) for detecting documented bacterial infection, even in the absence of fever 1
• Elevated total band count (>1,500/mm³) has the highest likelihood ratio (14.5) for bacterial infection 1
• Increased percentage of neutrophils (>90%) and band neutrophils (>16%) have likelihood ratios of 7.5 and 4.7, respectively 1

2. Severe Inflammatory Conditions

• Neutrophilia is a hallmark of acute lung inflammation in conditions like ALI/ARDS 1
• Bronchoalveolar lavage fluid from patients with acute lung injury contains increased quantities of neutrophils and their enzymes, which correlate with severity of lung injury 1

3. Refractory Asthma

• Increased neutrophils in airways distinguish refractory asthma from milder forms 1
• Neutrophils are present in higher quantities in airways of patients with refractory asthma compared to mild asthma or normal controls 1
• Increased neutrophils are seen in patients dying of status asthmaticus, particularly when death occurs within hours of attack 1

4. Chronic Inflammatory Disorders

• Persistent neutrophilia may indicate chronic inflammatory diseases such as atherosclerosis, diabetes mellitus, nonalcoholic fatty liver disease, or autoimmune disorders 3

5. Hematologic Malignancies

• Persistent unexplained neutrophilia warrants evaluation for hematologic malignancies 2

Diagnostic Approach

Initial Workup

1. Complete blood count with differential to confirm neutrophilia
2. Blood cultures (at least 2 sets) if infection is suspected
3. Serum protein electrophoresis to assess for hypogammaglobulinemia or paraproteinemia
4. Chest radiograph as baseline, with additional imaging based on symptoms 2

Secondary Evaluation

• If infection is suspected: targeted cultures based on symptoms
• If hematologic malignancy is suspected: flow cytometry of peripheral blood, bone marrow aspiration and biopsy with cytogenetics 2
• Consider bone marrow examination if there are persistent unexplained cytopenias or no obvious cause identified after initial workup 2

Common Etiologies of Neutrophilia

1. Infections (most common cause)

   • Bacterial infections (particularly acute)
   • Certain viral and fungal infections

2. Inflammatory conditions

   • Autoimmune disorders
   • Tissue damage/necrosis
   • Vasculitis

3. Hematologic disorders

   • Myeloproliferative disorders
   • Leukemias

4. Medications

   • Corticosteroids
   • Lithium
   • G-CSF/GM-CSF

5. Other causes

   • Stress/exercise
   • Smoking
   • Obesity
   • Obstructive sleep apnea 4

Clinical Implications

• Neutrophilia with left shift (increased bands) strongly suggests bacterial infection requiring antimicrobial therapy 1
• In severe infections, neutrophilia may be accompanied by other signs of systemic inflammatory response syndrome
• Neutrophils can produce substances like matrix metalloproteinases and oxygen radicals that may alter structure and function of airways in asthma 1
• Corticosteroids may prolong survival of neutrophils by decreasing apoptosis, potentially contributing to persistent neutrophilia in patients on steroid therapy 1

Pitfalls to Avoid

1. Failing to obtain appropriate cultures before initiating antimicrobial therapy 2
2. Overlooking non-infectious causes of neutrophilia in patients without fever
3. Neglecting to evaluate for hematologic malignancies in cases of persistent unexplained neutrophilia
4. Using aminoglycosides as empiric therapy in spontaneous bacterial peritonitis due to risk of nephrotoxicity 2
5. Delaying empiric antibiotic therapy in suspected infection with neutrophilia 2

Monitoring and Follow-up

• Repeat CBC with differential in 1-2 weeks to assess trends
• Consider hematology consultation if initial workup is negative but abnormalities persist
• Daily assessment of fever trends and neutrophil counts until resolution in acute settings 2

By systematically evaluating patients with neutrophilia and understanding its clinical significance, clinicians can identify underlying conditions and initiate appropriate treatment to improve patient outcomes.