Definitions of Neutropenia and Neutropenic Fever
Neutropenia is defined as an absolute neutrophil count (ANC) <1,000 cells/mm³, with severe neutropenia at ANC <500 cells/mm³, and neutropenic fever is defined as a single oral temperature ≥38.3°C (101°F) or sustained temperature ≥38.0°C (100.4°F) for 1 hour in the presence of neutropenia. 1
Neutropenia Classification
The severity of neutropenia is stratified based on ANC thresholds, which directly correlates with infection risk:
- Mild neutropenia: ANC 1.0-1.5 × 10⁹/L (1,000-1,500 cells/mm³) 2
- Moderate neutropenia: ANC 0.5-1.0 × 10⁹/L (500-1,000 cells/mm³) 2
- Severe neutropenia: ANC <0.5 × 10⁹/L (<500 cells/mm³) 2
- Profound neutropenia: ANC <0.1 × 10⁹/L (<100 cells/mm³) 1
Protracted neutropenia is defined as neutropenia lasting ≥7 days, which significantly increases infection risk. 1
ANC Calculation
The ANC is calculated from the white blood cell (WBC) count multiplied by the percentage of neutrophils (segmented neutrophils plus bands). 2
Neutropenic Fever Definition
The most current guidelines provide two temperature thresholds for defining fever in neutropenic patients:
- Single oral temperature ≥38.3°C (101°F), OR 1
- Temperature ≥38.0°C (100.4°F) sustained over a 1-hour period 1
Critical Threshold for Neutropenic Fever
Neutropenic fever specifically requires ANC <500 cells/mm³ (or <1,000 cells/mm³ with predicted decline to <500 cells/mm³) combined with fever meeting the above temperature criteria. 1 Some sources define the threshold more stringently as ANC <0.5 × 10⁹/L with fever >38.5°C for >1 hour. 2
Clinical Significance
Infection risk increases dramatically when ANC falls below 500 cells/µL, with the highest risk occurring when neutrophils are <100/µL. 3 Patients with ANC <100 cells/µL lasting 3 weeks or more develop documented infections in nearly 100% of cases. 4
Duration Matters
The duration of neutropenia is as important as the depth. Patients with anticipated prolonged neutropenia (>7 days) face substantially higher infection risk compared to those with brief neutropenic episodes. 3
Common Pitfalls
Fever patterns in neutropenia are non-specific and may be the only sign of infection, as classic inflammatory signs are often absent due to lack of neutrophils. 4 Additionally, antipyretic effects of corticosteroids can suppress fever, potentially masking serious infection. 4
Even minor skin lesions in neutropenic patients can represent serious infections and require thorough evaluation. 3 Physical examination and laboratory findings may not display classic signs of infection in this population. 5