What can cause a low White Blood Cell (WBC) count?

Causes of Low White Blood Cell Count (Leukopenia)

Low white blood cell count can be caused by a wide range of conditions including infections, medications, autoimmune disorders, bone marrow disorders, and nutritional deficiencies. Understanding the specific cause is crucial for proper management and treatment.

Common Causes of Leukopenia

Infections

• Viral infections (particularly CMV, HHV6, EBV, parvovirus, HIV) 1
• Overwhelming bacterial infections (especially when causing sepsis)
• Tuberculosis
• Typhoid fever

Medications and Toxins

• Chemotherapy drugs
• Immunosuppressants
• Antibiotics (particularly chloramphenicol, sulfonamides)
• Antipsychotics (clozapine)
• Antithyroid medications
• Radiation exposure 2
• Benzene and other chemical toxins

Bone Marrow Disorders

• Acute leukemias
• Myelodysplastic syndromes
• Aplastic anemia (hypocellular marrow with marrow cellularity <25%) 2
• Myelofibrosis
• Bone marrow infiltration by cancer

Autoimmune Disorders

• Systemic lupus erythematosus
• Rheumatoid arthritis
• Felty's syndrome
• Autoimmune neutropenia

Nutritional Deficiencies

• Vitamin B12 deficiency
• Folate deficiency
• Copper deficiency 2

Other Causes

• Hypersplenism (increased splenic sequestration)
• Congenital disorders (cyclic neutropenia, Kostmann syndrome)
• Post-viral bone marrow suppression
• Alcoholism
• Severe liver disease

Diagnostic Approach

When evaluating leukopenia, the following diagnostic workup is recommended:

1. Complete blood count with differential to determine which white cell lines are affected 2, 1
2. Peripheral blood smear to evaluate cell morphology 2
3. Reticulocyte count to assess bone marrow response 2
4. Viral studies including CMV, HHV6, EBV, parvovirus, and HIV 2
5. Nutritional assessments including B12, folate, iron, copper, and ceruloplasmin levels 2
6. Serum LDH and renal function tests 2
7. Bone marrow biopsy and aspirate analysis if primary bone marrow disorder is suspected 2

Severity Assessment

The severity of leukopenia is typically graded based on the absolute neutrophil count (ANC):

• Grade 1: ANC 1,500-2,000/mm³
• Grade 2: ANC 1,000-1,500/mm³
• Grade 3: ANC 500-1,000/mm³
• Grade 4: ANC <500/mm³ (severe neutropenia with high infection risk) 2

Management Considerations

Management depends on the underlying cause and severity:

• Infection-related leukopenia: Treat the underlying infection
• Drug-induced leukopenia: Discontinue the offending medication when possible
• Severe neutropenia (ANC <500): Consider growth factor support and close clinical monitoring 2
• Aplastic anemia: May require immunosuppressive therapy (ATG + cyclosporine) or bone marrow transplantation 2
• Nutritional deficiencies: Supplement the deficient nutrient

Warning Signs Requiring Urgent Attention

• Fever in a neutropenic patient (neutropenic fever)
• Signs of infection with ANC <500/mm³
• Rapidly falling WBC counts
• Associated abnormalities in other blood cell lines
• Systemic symptoms (weight loss, night sweats, lymphadenopathy)

Key Points to Remember

• Leukopenia is often transient and benign, especially when related to viral infections
• The risk of infection increases significantly when the ANC falls below 500/mm³
• Always consider medication review in patients with unexplained leukopenia
• Bone marrow disorders should be suspected when leukopenia is accompanied by abnormalities in other blood cell lines
• Nutritional causes should not be overlooked, especially in elderly or malnourished patients

Proper identification of the underlying cause is essential for appropriate management of leukopenia and prevention of complications.