What are some benign causes of leukopenia (low white blood cell count)?

Benign Causes of Leukopenia (Low White Blood Cell Count)

Leukopenia (low white blood cell count) can have numerous benign causes that do not necessarily indicate a serious underlying condition. Understanding these causes is important for proper clinical management and to avoid unnecessary concern.

Medication-Related Causes

• Chemotherapy agents are among the most common causes of leukopenia through bone marrow suppression 1, 2
• Immunosuppressive medications such as azathioprine and 6-mercaptopurine used in autoimmune disorders and inflammatory bowel disease can cause bone marrow toxicity leading to leukopenia 1, 2
• Thiopurines can cause severe bone marrow toxicity, especially in patients with thiopurine methyltransferase (TPMT) deficiency 2
• Various prescription and non-prescription drugs can cause leukopenia as an adverse effect 1

Infection-Related Causes

• Viral infections, particularly HIV and HCV, can cause leukopenia 1
• Cytomegalovirus infection can lead to cytopenias, including leukopenia 1
• Bacterial infections, especially overwhelming sepsis, can cause leukopenia due to increased utilization and destruction of white blood cells 3
• Influenza A in children commonly presents with a low white blood cell count (WBC <4 in 8-27% of cases) 4

Physiological and Benign Conditions

• Ethnic neutropenia: Some ethnic groups, particularly those of African descent, have constitutionally lower neutrophil counts that are benign 1
• Splenic sequestration: An enlarged spleen can trap white blood cells, causing mild leukopenia 5
• Pseudoleukopenia: Laboratory artifacts such as EDTA-dependent agglutination can cause falsely low white blood cell counts 1, 6
• Nutritional deficiencies: Vitamin B12 or folate deficiency can lead to megaloblastic anemia with associated leukopenia 5

Autoimmune-Related Causes

• Autoimmune disorders can cause leukopenia through immune-mediated destruction of white blood cells 1
• Autoimmune neutropenia is a benign condition, especially common in children 5
• Systemic lupus erythematosus and rheumatoid arthritis can present with leukopenia as part of their clinical manifestations 1

Diagnostic Approach for Leukopenia

• Complete blood count (CBC) with differential is essential to characterize the type of leukopenia and presence of other cytopenias 3
• Examination of peripheral blood smear helps determine which white blood cell lines are affected and to look for morphological abnormalities 1
• Previous blood counts should be checked to understand the dynamic development of the leukopenia 7
• Assessment of red blood cell and platelet counts is important; bi- or pancytopenia usually implies insufficient production in the bone marrow 7

Management Considerations

• For medication-induced leukopenia, consider dose reduction or discontinuation of the offending agent 1
• For autoimmune-mediated leukopenia, corticosteroids are often the first-line treatment 2
• The risk of infection increases significantly when neutrophil counts fall below 500/mcL, with the highest risk at counts below 100/mcL 2
• Febrile neutropenia requires immediate antibiotic therapy to prevent serious complications 1

Common Pitfalls and Caveats

• EDTA-dependent agglutination can cause pseudoleukopenia and should be excluded when evaluating cytopenias 1, 6
• Leukopenia in children with influenza is common and does not necessarily indicate a serious condition 4
• Ethnic variations in normal white blood cell counts should be considered before diagnosing leukopenia 1
• Transient leukopenia may occur following viral infections and typically resolves without specific treatment 5

Understanding these benign causes of leukopenia can help clinicians avoid unnecessary investigations and treatments while ensuring appropriate monitoring for patients with low white blood cell counts.