What causes leukopenia and neutropenia, especially during an infection?

Causes of Low White Blood Count and Neutropenia During Infection

The most common causes of leukopenia and neutropenia during infection include the infection itself consuming neutrophils faster than they can be produced, cancer treatments, certain medications, bone marrow disorders, and autoimmune conditions. 1

Mechanisms of Leukopenia and Neutropenia

Leukopenia (white blood count <4,000/mcL) and neutropenia (absolute neutrophil count <1,500/mcL) can occur through several mechanisms:

1. Infection-Related Causes

• Increased consumption: During active infection, neutrophils are rapidly deployed to fight pathogens, potentially causing a temporary decrease in circulating levels 1
• Bone marrow suppression: Certain infections directly suppress bone marrow production
• Common pathogens: Bacterial (gram-negative and gram-positive), viral (HSV, VZV, influenza), and fungal organisms can all contribute 1

2. Cancer-Related Causes

• Chemotherapy: Directly suppresses bone marrow production 1
• Radiation therapy: Damages bone marrow stem cells
• Malignancy itself: Cancer can invade bone marrow or create paraneoplastic effects 1
• Solid tumors: Can cause leukopenia through:
  • Necrotic tumor tissue forming infection nidus
  • Obstruction (e.g., endobronchial tumors causing pneumonia)
  • Direct invasion of tissues 1

3. Medication-Related Causes

• Chemotherapeutic agents: Particularly those affecting rapidly dividing cells
• Antibiotics: Some can cause bone marrow suppression
• Immunosuppressants: Affect white blood cell production or function

4. Other Important Causes

• Autoimmune disorders: Conditions like systemic lupus erythematosus can cause leukopenia in 22-42% of cases 2
• Nutritional deficiencies: Particularly B12 and folate deficiency (megaloblastosis) 3
• Hypersplenism: Excessive sequestration of blood cells in the spleen 3
• Primary bone marrow disorders: Leukemias, myelodysplastic syndromes 3
• COVID-19 infection: Can cause neutropenia even in asymptomatic cases 4

Risk Assessment and Clinical Significance

The severity and clinical impact of neutropenia depend on several factors:

• Neutrophil count: Risk increases significantly when counts fall below 500/mcL and is greatest below 100/mcL 1
• Duration of neutropenia: Prolonged neutropenia (>10 days) significantly increases infection risk 1
• Rate of decline: Rapid drops indicate poor bone marrow reserve 1
• Mucosal barrier integrity: Chemotherapy and radiation can damage mucosal barriers, increasing infection risk 1

Infection Risk During Neutropenia

• Approximately 50-60% of febrile neutropenic patients have an established or occult infection 1
• 10-20% of patients with neutrophil counts <100/mcL will develop bloodstream infections 1
• Common infection sites include:
  • Alimentary tract (mouth, pharynx, esophagus, bowel)
  • Sinuses
  • Lungs
  • Skin 1

Management Considerations

1. Identify underlying cause: Determine whether neutropenia is due to decreased production or increased destruction 3

2. Infection management:

   • Early antimicrobial therapy for febrile neutropenia
   • Empiric coverage for both gram-positive and gram-negative organisms 1

3. Growth factor consideration:

   • Filgrastim (G-CSF) can be used to stimulate neutrophil production in appropriate cases 5
   • Indicated to decrease infection incidence in patients receiving myelosuppressive chemotherapy 5

4. Monitoring:

   • Regular blood count monitoring
   • Vigilance for subtle signs of infection (fever may be the only sign) 1

Important Caveats

• Neutropenic patients may have minimal or absent signs of inflammation due to lack of neutrophils 1
• Fever remains an important early sign of infection in neutropenic patients 1
• The increase in your white blood cell count from 2.2 to 2.9 during infection suggests some bone marrow response, but remains significantly below normal 1
• Patients with severe neutropenia may require prophylactic antimicrobials and/or growth factors depending on the underlying cause and duration 1

Remember that neutropenia during infection creates a dangerous cycle: the infection consumes neutrophils while simultaneously requiring them to fight the pathogen, potentially worsening the neutropenia and increasing infection risk.