Definition of Neutropenia
Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1,500 cells/μL, with severe neutropenia defined as ANC < 500 cells/μL, and profound neutropenia as ANC < 100 cells/μL. 1, 2
Classification of Neutropenia by Severity
Neutropenia is classified according to the severity of neutrophil count reduction:
| Grade | Neutrophil Count |
|---|---|
| 0 | ≥2,000 cells/μL |
| 1 | 1,500-2,000 cells/μL |
| 2 | 1,000-1,500 cells/μL |
| 3 | 500-1,000 cells/μL |
| 4 | <500 cells/μL |
The risk of infection increases as the neutrophil count decreases, with the greatest risk occurring when counts fall below 500 cells/μL 1, 2.
Clinical Significance of Different Neutropenia Levels
- Mild neutropenia (ANC 1,000-1,500 cells/μL): Minimal increased risk of infection
- Moderate neutropenia (ANC 500-1,000 cells/μL): Moderate increased risk of infection
- Severe neutropenia (ANC < 500 cells/μL): Significantly increased risk of infection
- Profound neutropenia (ANC < 100 cells/μL): Highest risk of life-threatening infections 1, 2, 3
Additional Important Definitions
Febrile neutropenia: Defined as a single oral temperature of ≥38.3°C (101°F) or a temperature ≥38.0°C (100.4°F) sustained over a 1-hour period in a patient with neutropenia 1
Predicted neutropenia: A count of ≤1,000 cells/μL with a predicted decrease to ≤500 cells/μL is also considered neutropenia requiring clinical attention 1
Chronic neutropenia: Neutropenia lasting for 3 months or longer 4, 3
Protracted neutropenia: Neutropenia lasting for ≥7 days 1
Clinical Implications
The clinical significance of neutropenia depends on:
- Severity: The lower the neutrophil count, the higher the risk of infection
- Duration: Prolonged neutropenia (>7 days) significantly increases infection risk
- Rate of decline: Rapidly declining counts may indicate more serious underlying conditions
- Underlying cause: Neutropenia due to bone marrow disorders carries higher morbidity and mortality than drug-induced causes
Patients with severe neutropenia (ANC < 500 cells/μL) are at substantially increased risk for bacterial and fungal infections, with infection risk being inversely proportional to the neutrophil count 1, 2. The frequency and severity of infections increase dramatically when counts fall below 500 cells/μL, and patients with counts below 100 cells/μL are at the highest risk 1, 3.
Common Pitfalls in Managing Neutropenia
- Failing to recognize the significance of neutropenia severity and duration
- Overlooking the need for immediate evaluation in severe neutropenia (ANC < 500 cells/μL)
- Not considering both the absolute neutrophil count and the predicted decline when assessing risk
- Underestimating infection risk in patients with chronic neutropenia even at moderate levels
Understanding the definition and classification of neutropenia is crucial for appropriate risk assessment and management decisions that directly impact patient morbidity and mortality.