What causes leucocytopenia (low white blood cell count)?

Causes of Leukocytopenia (Low White Blood Cell Count)

Leukocytopenia is primarily caused by reduced production of white blood cells, increased destruction, or both, with the most common causes being infections, drugs, malignancies, autoimmune disorders, and bone marrow diseases. 1

Common Causes of Leukocytopenia

Infections

• Viral infections (HIV, hepatitis C, Epstein-Barr virus, cytomegalovirus, varicella zoster) can cause leukocytopenia through direct bone marrow suppression or immune-mediated mechanisms 2
• Bacterial infections can lead to increased utilization and destruction of white blood cells during the immune response 1
• Parasitic infections such as malaria can cause leukopenia through hypersplenism and bone marrow suppression 3

Medication-Induced

• Chemotherapy agents commonly cause bone marrow suppression leading to leukocytopenia 4
• Immunosuppressive medications used in autoimmune disorders 4
• Certain antibiotics, antipsychotics, and anticonvulsants can cause allergic agranulocytosis 3
• Immune checkpoint inhibitors can induce hematologic immune-related adverse events including leukopenia 4

Autoimmune Disorders

• Systemic lupus erythematosus (SLE) is associated with leukopenia in 22-41.8% of cases, lymphopenia in 15-82%, and neutropenia in 20-40% of patients 5
• Autoimmune neutropenia and immunoneutropenia can occur as primary disorders or secondary to other autoimmune conditions 1
• Autoimmune hemolytic anemia and immune thrombocytopenia may coexist with leukopenia in conditions like Evans syndrome 2

Hematologic Malignancies

• Chronic lymphocytic leukemia (CLL) can cause cytopenias through bone marrow infiltration or immune-mediated mechanisms 4
• Lymphoproliferative disorders including large granular T-lymphocyte leukemia can cause leukopenia 2
• Myelodysplastic syndromes impair normal blood cell production in the bone marrow 4

Bone Marrow Disorders

• Aplastic anemia causes pancytopenia including leukopenia 4
• Megaloblastic anemia due to vitamin B12 or folate deficiency can lead to leukopenia 1
• Primary bone marrow failure syndromes 6

Hypersplenism

• Enlarged spleen can sequester and destroy white blood cells leading to peripheral leukopenia 3
• Seen in portal hypertension, liver cirrhosis, and certain hematologic disorders 1

Other Causes

• Radiation exposure suppresses bone marrow function 6
• Congenital disorders (rare hereditary neutropenias) 1
• Post-transplant immunosuppression 4
• Nutritional deficiencies (severe malnutrition) 6

Clinical Significance and Risk Assessment

• The risk of infection increases significantly when neutrophil counts fall below 500/mcL 4
• The frequency and severity of infection are inversely proportional to the neutrophil count, with highest risk (10-20%) at counts below 100/mcL 4
• Patients with cancer and leukopenia are at particularly high risk for infectious complications 4
• In patients with HIV, leukopenia may increase the risk of opportunistic infections 4
• Patients with autoimmune disorders may have increased susceptibility to infections when leukopenic, especially if also on immunosuppressive therapy 4

Diagnostic Approach

• Any leukopenia below 1000/μL requires immediate investigation due to life-threatening risk 3
• Complete blood count with differential to determine which white cell lines are affected 6
• Bone marrow aspiration and biopsy may be necessary to evaluate cell production 3
• Medication review to identify potential drug causes 1
• Evaluation for underlying infections, autoimmune disorders, or malignancies 6
• Assessment of spleen size to evaluate for hypersplenism 3

Management Considerations

• Treatment should target the underlying cause of leukocytopenia 1
• Discontinuation of offending medications when drug-induced 3
• Antimicrobial prophylaxis may be indicated in severe neutropenia, especially in cancer patients 4
• Growth factors (G-CSF) may be considered in severe cases, though evidence in autoimmune conditions is limited 5
• For autoimmune-mediated leukopenia, corticosteroids are often the first-line treatment 4
• In patients with febrile neutropenia, prompt antibiotic therapy is essential 4
• Monitoring frequency should be based on the severity of leukopenia and underlying condition 4