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

Causes of Low White Blood Cell Count (Leukopenia)

Leukopenia (low white blood cell count) is most commonly caused by infections, medications, malignancies, and primary bone marrow disorders. 1 Understanding the underlying cause is essential for appropriate management and preventing complications.

Common Causes of Leukopenia

Infections

• Viral infections are a leading cause of transient leukopenia 2
• Bacterial infections, particularly overwhelming sepsis, can cause leukopenia due to increased utilization and destruction of white blood cells 3
• Tuberculosis treatment regimens containing rifampicin and isoniazid can lead to leukopenia in approximately 1.2% of men and 5.9% of women 4

Medication-Induced Leukopenia

• Chemotherapy agents are a major cause of leukopenia through bone marrow suppression 3
• Antimicrobial drugs, particularly anti-tuberculosis medications, can cause leukopenia 4
• Other medications commonly associated with leukopenia include certain anticonvulsants, antipsychotics, and immunosuppressants 2

Malignancies and Bone Marrow Disorders

• Hematologic malignancies, including leukemias and lymphomas, can present with leukopenia 3
• Bone marrow infiltration by malignant cells can disrupt normal white blood cell production 5
• Myelodysplastic syndromes can lead to ineffective hematopoiesis resulting in leukopenia 3

Autoimmune Disorders

• Immunoneutropenia (autoimmune destruction of neutrophils) 1
• Systemic lupus erythematosus and other autoimmune conditions can cause leukopenia through multiple mechanisms 2

Other Causes

• Hypersplenism can lead to increased sequestration and destruction of white blood cells 1
• Nutritional deficiencies, particularly vitamin B12 and folate deficiency (megaloblastosis) 1
• Primary immunodeficiency disorders can present with leukopenia 3
• Congenital neutropenias are rare hereditary conditions 1

Evaluation of Leukopenia

Initial Assessment

• Complete blood count (CBC) with differential to characterize the type of leukopenia and presence of other cytopenias 3
• Peripheral blood smear examination is essential to identify abnormal cell morphology and provide clues to etiology 2
• Review of medication history to identify potential causative agents 2

Further Workup Based on Clinical Suspicion

• Bone marrow examination if primary bone marrow disorder is suspected, especially with concurrent abnormalities in red blood cell or platelet counts 5
• Infectious disease workup including blood cultures if infection is suspected 6
• Immunologic testing if autoimmune or immunodeficiency disorders are suspected 3

Management Considerations

General Approach

• Identify and treat the underlying cause when possible 1
• Discontinue suspected causative medications when appropriate 4
• Monitor white blood cell counts regularly to assess progression or resolution 2

Management of Severe Neutropenia

• Febrile neutropenia (temperature >38.5°C with ANC <0.5 × 10^9/L) requires immediate antibiotic therapy 3
• Consider prophylactic antimicrobials in prolonged neutropenia based on institutional protocols 6
• Avoid invasive procedures in patients with severe neutropenia due to risk of complications 3

Role of Growth Factors

• Granulocyte colony-stimulating factor (G-CSF) may be considered in high-risk situations or severe neutropenia 3
• G-CSF is contraindicated during chest radiotherapy due to increased risk of complications 3
• Growth factors should not be used routinely in patients without neutropenia 3

Special Considerations

Oncology Patients

• Chemotherapy-induced neutropenia is expected and often managed with supportive care 3
• Dose adjustments of chemotherapy may be necessary in patients with prolonged or severe neutropenia 3
• Monitor for tumor lysis syndrome in patients with malignancy-related leukopenia 6

Immunocompromised Patients

• HIV-infected patients may require more frequent viral load monitoring if treatment is anticipated to cause lymphopenia 3
• Opportunistic infection prophylaxis should be considered in patients with CD4+ T-cell suppression 3

Emergency Situations

• Patients with agranulocytosis (severe neutropenia) and fever require immediate hospitalization and broad-spectrum antibiotics 2
• White blood cell counts above 100,000/mm³ represent a medical emergency due to risk of brain infarction and hemorrhage 5

Understanding the specific cause of leukopenia is crucial for appropriate management and prevention of complications. The approach should be tailored based on the severity, associated symptoms, and underlying conditions.