What are the implications of having low neutrophils (neutropenia)?

Implications of Low Neutrophils (Neutropenia)

Low neutrophil counts significantly increase infection risk, with severe neutropenia (<500/mcL) requiring immediate medical attention due to potentially life-threatening complications. 1

Definition and Classification

Neutropenia is defined as an absolute neutrophil count (ANC) below 1500 cells/mm³, and is classified as:

• Mild: 1000-1500 cells/mm³
• Moderate: 500-1000 cells/mm³
• Severe: <500 cells/mm³ 2

Febrile neutropenia is specifically defined as a temperature >38.5°C for >1 hour with an ANC <500 cells/mm³. 1

Clinical Implications

Infection Risk

The risk of infection is directly proportional to:

1. Severity of neutropenia - Risk increases dramatically when ANC falls below 500/mcL
2. Duration of neutropenia - Prolonged neutropenia significantly increases infection risk
3. Rate of ANC decline - Rapid drops indicate poor bone marrow reserve 1

When ANC falls below 100/mcL, approximately 10-20% of patients will develop bloodstream infections. 1

Common Infection Sites

Primary infection sites in neutropenic patients include:

• Alimentary tract (mouth, pharynx, esophagus, intestines)
• Sinuses
• Lungs
• Skin 1

Causative Pathogens

Pathogens commonly causing infections in neutropenic patients:

• Early infections: Primarily bacterial

  • Gram-positive: Coagulase-negative staphylococci, S. aureus, viridans streptococci, enterococci
  • Gram-negative: E. coli, Klebsiella, Enterobacter, Pseudomonas aeruginosa

• Later infections:

  • Antibiotic-resistant bacteria
  • Fungi (Candida, Aspergillus)
  • Viruses (HSV, RSV, influenza) 1

Clinical Presentation

Neutropenic patients often present with:

• Muted signs and symptoms of infection due to lack of neutrophils
• Fever as an early but nonspecific sign
• Oral ulcers and inflammation
• Recurrent skin infections 1, 3

Management Considerations

Infection Prevention

For patients with severe neutropenia:

• Prompt evaluation of fever (>38.5°C)
• Early initiation of empiric antibiotics for febrile neutropenia
• Consider prophylactic antibiotics in high-risk patients

Growth Factor Therapy

Hematopoietic growth factors (G-CSF, pegfilgrastim) may be indicated:

• Primary prophylaxis: Only when risk of febrile neutropenia exceeds 20% with chemotherapy
• Treatment of established febrile neutropenia: Only in settings with increased morbidity/mortality (sepsis, tissue infection, prolonged neutropenia) 1

Growth factors should be avoided in patients with infections not related to neutropenia, such as community or hospital-acquired pneumonia. 1

Dosing of G-CSF

When indicated:

• 5 μg/kg/day subcutaneously, starting 24-72 hours after chemotherapy
• Continue until sufficient post-nadir ANC recovery
• Pegfilgrastim: Single dose of 6 mg subcutaneously 1, 4

Special Considerations

Risk Factors for Complications

Patients at higher risk for complications include those with:

• ANC <100/mcL
• Prolonged neutropenia (>7 days)
• Rapid decline in neutrophil count
• Comorbidities
• Advanced age
• Poor nutritional status
• Disrupted mucosal barriers (mucositis) 1

Contraindications for Growth Factors

• G-CSF is contraindicated during radiotherapy to the chest due to increased complications and mortality
• Avoid administering immediately before or with chemotherapy due to risk of worsening thrombocytopenia 1

Evaluation of Neutropenia

For patients with newly identified neutropenia:

1. Confirm neutropenia with repeat testing
2. Examine blood smear
3. Review medical and family history
4. Consider bone marrow examination and cytogenetic testing for severe or persistent neutropenia 3

Long-term Implications

Patients with certain types of chronic neutropenia (particularly congenital forms) may have increased risk of developing:

• Myelodysplastic syndrome (MDS)
• Acute myeloid leukemia (AML) 5

This risk may be higher in patients receiving long-term G-CSF therapy. 1