What causes a low white blood cell (WBC) count, or leukopenia?

Causes of Low White Blood Cell Count (Leukopenia)

Leukopenia can be caused by a wide range of conditions including medications, infections, bone marrow disorders, nutritional deficiencies, and congenital disorders, with treatment focused on addressing the underlying cause. 1

Primary Causes of Leukopenia

Medication-Induced Causes

• Medications: Many drugs can cause leukopenia through bone marrow suppression
  • Immunosuppressants (e.g., azathioprine) 1
  • Sulfonamides (can cause agranulocytosis, aplastic anemia, leukopenia) 2
  • Chemotherapeutic agents
  • Antipsychotics
  • Anticonvulsants

Hematologic Disorders

• Acute leukemias including acute promyelocytic leukemia 1
• Bone marrow failure syndromes
  • Aplastic anemia
  • Myelodysplastic syndromes
• Myelofibrosis

Infectious Causes

• Viral infections
  • HIV/AIDS
  • Hepatitis
  • Influenza
  • Epstein-Barr virus
  • Cytomegalovirus
• Bacterial infections
  • Typhoid fever
  • Tuberculosis
  • Overwhelming bacterial infections (sepsis)
• Parasitic infections
  • Malaria
  • Leishmaniasis

Nutritional Deficiencies

• Vitamin B12 deficiency 1
• Folate deficiency 1
• Copper deficiency

Autoimmune Disorders

• Systemic lupus erythematosus
• Rheumatoid arthritis
• Adult-onset Still's disease 1

Congenital Disorders

• Severe combined immunodeficiency (SCID) 1
• Kostmann syndrome (severe congenital neutropenia)
• Cyclic neutropenia
• Immuno-osseous dysplasias 3

Other Causes

• Hypersplenism - excessive sequestration of blood cells in the spleen 4
• Physical or emotional stress (can cause redistribution of white blood cells) 5
• Radiation exposure

Classification of Leukopenia

The World Health Organization classifies leukopenia as 1:

• Mild: WBC 3,000-4,000/mm³
• Moderate: WBC 2,000-3,000/mm³
• Severe: WBC <2,000/mm³

Agranulocytosis (absolute neutrophil count <500/mm³) is considered a medical emergency 1

Diagnostic Approach

1. Complete blood count (CBC) with differential to confirm leukopenia and identify affected cell lines 1
2. Peripheral blood smear to evaluate cell morphology and identify dysplastic changes 6
3. Review of medication history to identify potential drug causes
4. Assessment of infection risk based on absolute neutrophil count
5. Bone marrow examination if cause remains unclear or primary bone marrow disorder is suspected

Management Principles

Management depends on the severity, duration, and underlying cause:

1. Treat the underlying cause:

   • Discontinue offending medications
   • Treat infections
   • Correct nutritional deficiencies

2. For severe neutropenia:

   • Consider granulocyte colony-stimulating factors
   • Implement infection prevention measures
   • Provide prompt antibiotic therapy for febrile neutropenia 1

3. For chronic leukopenia:

   • Regular monitoring of blood counts
   • Vigilance for signs of infection
   • Antimicrobial prophylaxis in prolonged severe neutropenia 1

Common Pitfalls in Management

• Overlooking medication causes of leukopenia 1
• Focusing only on the white blood cell count without considering other cell lines 1
• Delayed treatment of febrile neutropenia, which is a medical emergency 1
• Attributing leukopenia to a known condition without considering new or alternative diagnoses 1

Special Considerations

• Patients with chronic neutropenia may adapt and not develop infections despite very low neutrophil counts
• The risk of infection increases dramatically with neutrophil counts below 500/mm³
• Leukopenia in the context of pancytopenia suggests a bone marrow production problem rather than isolated white cell destruction

Understanding the specific cause of leukopenia is crucial for appropriate management and prevention of complications.