What is the initial step in the workup of a patient with neutropenia (low neutrophil count)?

Initial Workup of Neutropenia

The initial step in the workup of a patient with neutropenia should include a thorough history, physical examination, blood cultures, and complete blood count with differential to determine the severity, chronicity, and potential causes of the neutropenia. 1

Definition and Risk Stratification

Neutropenia is defined as an absolute neutrophil count (ANC) less than 1,500 cells/μL and can be categorized by severity:

• Mild: 1,000-1,500 cells/μL
• Moderate: 500-1,000 cells/μL
• Severe: <500 cells/μL 2

The risk of infection increases significantly with:

• ANC <500 cells/μL
• Prolonged duration (>7 days)
• Rapid decline in neutrophil count 1

Initial Diagnostic Approach

Step 1: Determine Severity and Risk

1. Calculate the absolute neutrophil count
2. Assess for signs of infection (fever, localized symptoms)
3. Evaluate risk factors using the MASCC score (for febrile neutropenia):
   • Score ≥21 indicates low risk (6% complication rate)
   • Score <21 indicates high risk 3

Step 2: Immediate Diagnostic Tests

• Complete blood count with differential
• Blood cultures (at least 2 sets)
• Comprehensive metabolic panel
• Chest radiograph
• Additional cultures from suspected sites of infection 1, 3

Step 3: Evaluate for Underlying Causes

• Medication history (chemotherapy, antibiotics, anticonvulsants)
• Recent infections
• Underlying hematologic disorders
• Autoimmune conditions
• Family history of neutropenia 4

Management Based on Presentation

For Febrile Neutropenia (Medical Emergency)

1. Immediate blood cultures and cultures from suspected infection sites
2. Prompt initiation of broad-spectrum antibiotics (within 2 hours)
   • Monotherapy with anti-pseudomonal β-lactam (cefepime, meropenem, or piperacillin-tazobactam)
   • Add vancomycin only for specific indications (catheter infection, MRSA colonization, skin/soft tissue infection) 3

For Afebrile Neutropenia

1. Determine chronicity (acute vs. chronic)
2. For chronic neutropenia (>3 months), consider:
   • Bone marrow aspiration and biopsy
   • Cytogenetic analysis
   • Flow cytometry
   • Genetic testing for congenital neutropenias 4

Special Considerations

Cancer Patients

• Risk stratify based on anticipated duration of neutropenia:
  • Low risk: <7 days of neutropenia
  • High risk: >10 days of neutropenia or profound neutropenia (ANC <100 cells/μL)
• Consider prophylactic antibiotics (fluoroquinolones) for high-risk patients 1

Congenital Neutropenias

• Bone marrow examination
• Genetic testing for known mutations
• Consider G-CSF therapy based on severity and infection history 1

Common Pitfalls to Avoid

1. Delayed evaluation of febrile neutropenia - This is a medical emergency requiring immediate intervention
2. Failure to obtain adequate cultures before starting antibiotics
3. Inappropriate use of growth factors without clear indications
4. Missing drug-induced neutropenia - Always review medication history
5. Overlooking chronic neutropenia that may indicate underlying hematologic disorders 3

Follow-up Recommendations

• For mild, asymptomatic neutropenia: Serial CBCs to monitor trends
• For moderate neutropenia: More frequent monitoring and consideration of bone marrow evaluation if persistent
• For severe neutropenia: Consider G-CSF therapy, especially with recurrent infections 1

The workup of neutropenia requires a systematic approach focusing on identifying the underlying cause while simultaneously assessing infection risk. Early recognition and appropriate management are crucial to prevent serious complications, particularly in patients with severe neutropenia.