At what absolute neutrophil count (ANC) do you classify a patient as having neutropenia?

Neutropenia Classification Thresholds

Neutropenia is classified when the absolute neutrophil count (ANC) falls below 1,500 cells/µL (or 1.5 × 10⁹/L), with severity grading determining clinical management and infection risk. 1, 2

Standard Classification System

The severity of neutropenia is graded as follows:

• Mild neutropenia: ANC 1,000-1,500 cells/µL (1.0-1.5 × 10⁹/L) 1, 2
• Moderate neutropenia: ANC 500-1,000 cells/µL (0.5-1.0 × 10⁹/L) 1, 2
• Severe neutropenia: ANC <500 cells/µL (<0.5 × 10⁹/L) 1, 2
• Profound neutropenia/Agranulocytosis: ANC <100-200 cells/µL 1, 3

Clinical Significance by Severity Level

The critical threshold for clinical management is ANC <500 cells/µL, which triggers specific interventions including prophylactic antimicrobial therapy in high-risk patients and defines febrile neutropenia protocols. 1

Mild Neutropenia (1,000-1,500 cells/µL)

• No antimicrobial prophylaxis required 1
• Regular CBC monitoring recommended 1
• Evaluate for underlying causes (autoimmune disease, hematologic malignancy, medications) 1
• If fever develops (>38.5°C for >1 hour), immediate evaluation is necessary despite mild neutropenia 1

Moderate Neutropenia (500-1,000 cells/µL)

• Evaluate underlying causes and consider bone marrow biopsy if etiology unclear 1
• Hold or adjust causative medications if identified 1
• No routine prophylactic antimicrobials unless additional risk factors present 1

Severe Neutropenia (<500 cells/µL)

• Implement broad-spectrum prophylactic antimicrobial therapy (fluoroquinolone with or without streptococcal coverage) 1, 4
• Daily clinical assessment and CBC monitoring until ANC ≥500 cells/µL 1
• Consider G-CSF therapy in specific clinical scenarios 4
• Continue antimicrobial prophylaxis until ANC recovers to ≥500 cells/µL 4

Profound Neutropenia (<100 cells/µL)

• Highest priority for prophylactic antimicrobials and close monitoring, especially if expected duration >7 days 1
• Very high risk of life-threatening infections 2
• Consider adding antiviral (acyclovir) and antifungal (fluconazole) prophylaxis 4

Febrile Neutropenia Definition

Febrile neutropenia is defined as fever >38.5°C for >1 hour with ANC <500 cells/µL and constitutes a medical emergency. 1, 4

Management requires:

• Immediate hospitalization and empiric broad-spectrum antibiotics 1
• Discontinue prophylactic fluoroquinolone if being used 4
• Obtain blood cultures, urine cultures, and chest X-ray before antibiotics 1
• Target gram-negative bacteria, particularly Pseudomonas aeruginosa 4

Important Clinical Caveats

• The ANC <500 cells/µL threshold applies to both current count and expected nadir within 48 hours, meaning prophylaxis should be initiated if neutrophil count is trending toward this level even if not yet reached 1
• In chemotherapy patients, even mild neutropenia may warrant closer monitoring 1
• Immunocompromised patients with mild neutropenia may require more aggressive evaluation 1
• Some ethnic populations have chronically lower baseline ANC values (benign ethnic neutropenia), which should not be confused with pathologic neutropenia 3, 5

ANC Calculation

ANC is calculated from: WBC count × (% segmented neutrophils + % bands) 1, 2