What do elevated neutrophils indicate?

What Elevated Neutrophils Indicate

Elevated neutrophils most commonly indicate bacterial infection, with an absolute band count ≥1,500 cells/mm³ carrying the highest diagnostic accuracy (likelihood ratio 14.5) for documented bacterial infection. 1

Primary Clinical Significance

Neutrophilia serves as a key marker for several distinct pathological processes:

Bacterial Infection (Most Common)

• Bacterial infections are the predominant cause of neutrophilia, with specific quantitative thresholds providing varying diagnostic accuracy 1
• An absolute band neutrophil count ≥1,500 cells/mm³ has the highest likelihood ratio (14.5) for detecting documented bacterial infection 1, 2
• Neutrophil percentage >90% carries a likelihood ratio of 7.5 for bacterial infection 1
• A left shift (≥16% band neutrophils) has a likelihood ratio of 4.7 for bacterial infection, even when total WBC count remains normal 1, 2
• Common bacterial sources include respiratory tract infections, urinary tract infections, skin/soft tissue infections, and gastrointestinal infections 1

Severe Inflammation and Tissue Damage

• Neutrophils play a dual role in inflammation—while essential for host defense, their hyperactivity can cause significant tissue damage 3
• In acute lung injury and ARDS, neutrophil-mediated inflammation causes alveolar epithelial damage, airspace flooding with plasma proteins, and surfactant depletion 4
• Bronchoalveolar lavage fluid from patients with acute lung injury contains increased neutrophils and their enzymes, both correlated with severity of lung injury 4
• Neutrophils produce matrix metalloproteinases and oxygen radicals that can profoundly alter tissue structure and function 4

Chronic Inflammatory Conditions

• In refractory asthma, neutrophils are present in higher quantities than in mild asthma or normal controls, representing a different inflammatory pattern less responsive to corticosteroids 4
• Patients dying of status asthmaticus within several hours show neutrophils as the predominant inflammatory cell 4
• In lung transplant recipients, BAL neutrophilia predicts subsequent development of bronchiolitis obliterans syndrome (BOS) 4
• Persistent bacterial colonization (particularly Pseudomonas) increases BAL neutrophils and inflammation markers 4

Non-Infectious Causes

• Medications including lithium, beta-agonists, and epinephrine can cause neutrophilia 1, 2
• Sterile inflammation from tissue damage releases damage-associated molecular patterns (DAMPs) that recruit neutrophils even without pathogens present 5

Diagnostic Approach Algorithm

Step 1: Quantify the Neutrophilia

• Obtain complete blood count with manual differential (automated analyzers cannot reliably assess band forms) 1, 2, 6
• Calculate absolute neutrophil count and absolute band count 1
• Assess for left shift (≥16% bands or ≥1,500 cells/mm³ absolute band count) 1, 2

Step 2: Assess Clinical Context

• Evaluate for signs of severe infection or sepsis: fever >38°C or hypothermia <36°C, hypotension, tachycardia, tachypnea, altered mental status, hyperlactatemia, or oliguria 6
• Identify potential infection sources: respiratory symptoms (cough, dyspnea, chest pain), urinary symptoms (dysuria, flank pain), skin/soft tissue findings (erythema, warmth, drainage), or gastrointestinal symptoms 1, 6
• Consider timing: neutrophils are first responders in acute inflammation but play complex roles in chronic conditions 3, 7, 8

Step 3: Targeted Diagnostic Testing

• Blood cultures if systemic infection suspected (bacteremia clinically likely) 1, 6
• Urinalysis with culture for urinary symptoms if pyuria present 1, 2
• Chest imaging for respiratory symptoms 1, 2
• Site-specific cultures as indicated by clinical presentation 1
• In cirrhosis patients with ascites: diagnostic paracentesis (neutrophil count >250 cells/mm³ in ascitic fluid indicates spontaneous bacterial peritonitis) 1

Step 4: Management Based on Severity

For severe sepsis/septic shock:

• Initiate broad-spectrum empiric antibiotics within 1 hour of recognition 6
• Aggressive fluid resuscitation for hypotension 6
• Source control measures (drainage, catheter removal) 6
• Vasopressor support if hypotension persists despite fluids 6

For stable patients:

• Complete diagnostic workup before initiating antibiotics 6
• Targeted antibiotic therapy based on suspected source and local resistance patterns 2, 6
• Close monitoring for clinical deterioration 6

Critical Pitfalls to Avoid

• Do not ignore left shift when total WBC is normal—this combination still indicates significant bacterial infection requiring evaluation 1, 2, 6
• Do not rely solely on automated analyzer flags—manual differential is mandatory for accurate band assessment 2, 6
• Do not overlook absolute neutrophil count elevation when total WBC is only mildly elevated 1
• Do not treat asymptomatic patients with antibiotics based solely on laboratory findings without clinical correlation 1, 6
• Do not delay antibiotics in severe sepsis/septic shock while awaiting culture results 6
• In older adults in long-term care, left shift has particular diagnostic importance due to decreased basal body temperature and frequent absence of typical infection symptoms 2

Special Considerations

Chronic Disease Context

• In idiopathic pulmonary fibrosis, BAL neutrophilia (>5%) occurs in 70-90% of patients and suggests underlying fibrosing process, though this finding is not specific 4
• Neutrophils contribute to chronic inflammatory diseases including atherosclerosis, diabetes mellitus, and autoimmune disorders through persistent low-grade inflammation 9
• Neutrophil heterogeneity exists with different functional phenotypes in cancer and chronic inflammation 8