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

Causes of Low White Blood Cell Count (Leukopenia)

Leukopenia is most commonly caused by medications, infections, bone marrow disorders, autoimmune conditions, and nutritional deficiencies, with the specific treatment approach depending on identifying the underlying cause. 1

Definition and Classification

Leukopenia refers to an abnormal reduction in circulating white blood cells, particularly neutrophils. According to the World Health Organization, leukopenia severity can be classified as:

• Mild: 3,000-4,000/mm³
• Moderate: 2,000-3,000/mm³
• Severe: <2,000/mm³ 1

Common Causes of Leukopenia

1. Medication-Induced

• Immunosuppressants: Azathioprine, 6-mercaptopurine 1
• Other medications: Various antibiotics, antipsychotics, antithyroid medications, chemotherapy agents

2. Infections

• Viral infections: Common cause, especially in children (CMV, EBV, HHV6, parvovirus) 1
• Overwhelming bacterial infections: Can cause leukopenia due to increased utilization and destruction of white blood cells 2
• Parasitic infections: Can lead to altered white blood cell counts

3. Bone Marrow Disorders

• Primary bone marrow disorders: Leukemia, myelodysplastic syndromes
• Bone marrow infiltration: From malignancies or other conditions
• Aplastic anemia: Failure of bone marrow to produce sufficient blood cells 2

4. Autoimmune Conditions

• Systemic lupus erythematosus
• Rheumatoid arthritis
• Adult-onset Still's disease: Can present with leukopenia during disease activity 3

5. Other Causes

• Hypersplenism: Excessive sequestration of blood cells in the spleen 2
• Nutritional deficiencies: Vitamin B12, folate, copper, zinc deficiencies 1
• Congenital disorders: Rare hereditary neutropenias, often associated with other developmental defects 2
• Inflammatory bowel disease: Associated with increased risk of neutropenia 1

Diagnostic Approach

When evaluating leukopenia, consider:

1. Review previous blood counts: Determine if the leukopenia is acute or chronic 4
2. Check other blood cell lines: Concurrent abnormalities in red blood cells or platelets suggest bone marrow issues 4
3. Peripheral blood smear: Essential for identifying cell morphology and potential causes 4
4. Medication review: Identify potential drug-induced causes
5. Nutritional assessment: Measure B12, folate, iron, copper, and zinc levels 1
6. Specialized testing: Flow cytometry for lymphocyte subpopulations, bone marrow evaluation when indicated 1

Clinical Implications and Management

The major concern with leukopenia, particularly neutropenia, is the increased risk of infection. Management should focus on:

1. Addressing the underlying cause:

   • Discontinuing offending medications
   • Treating underlying infections or inflammatory conditions
   • Managing primary bone marrow disorders 1

2. Infection prevention and treatment:

   • Antimicrobial prophylaxis for severe neutropenia
   • Prompt broad-spectrum antibiotics for febrile neutropenia (medical emergency) 4
   • Granulocyte colony-stimulating factors in selected cases 1

Special Considerations

• Severe neutropenia with fever: Constitutes a medical emergency requiring immediate broad-spectrum antibiotics 4
• Primary immunodeficiency disorders: May present with recurrent infections and require specific treatments including immunoglobulin replacement, hematopoietic stem cell transplantation, or gene therapy 1
• Pancytopenia: Should alert clinicians to possible hemophagocytic syndrome, which requires prompt immunosuppressive treatment 3

Understanding the cause of leukopenia is essential for appropriate management and prevention of potentially life-threatening complications.