What causes a decrease in white blood cell count?

What Lowers Your White Blood Cell Count

White blood cell count is most commonly lowered by chemotherapy and radiation therapy, bone marrow infiltration by cancer, nutritional deficiencies (vitamin B12, folate, iron), certain medications, autoimmune diseases, infections, and hypersplenism. 1

Medications and Cancer Treatments

Chemotherapy agents are the most common iatrogenic cause of decreased WBC, directly impairing hematopoiesis in the bone marrow through myelosuppressive effects that accumulate over repeated treatment cycles. 2, 1 Platinum-based regimens (used in lung, ovarian, and head and neck cancers) are particularly notorious for inducing leukopenia due to combined bone marrow and kidney toxicity. 2, 3

• Radiation therapy to bone marrow-containing areas (cranium, spine, pelvis) causes radiation-induced myelosuppression, with approximately one-third of patients developing grades 3-4 hematologic toxicity. 2, 1
• Certain antibiotics, anticonvulsants, and immunosuppressants can cause bone marrow suppression. 1
• Specific medications requiring WBC monitoring include clozapine, azathioprine, cyclophosphamide, and rifabutin due to their known risk of blood count suppression. 4

Bone Marrow Disorders and Cancer

Bone marrow infiltration by cancer cells directly suppresses normal hematopoiesis, affecting white cell production. 1 This occurs in:

• Leukemia, particularly in advanced stages, which suppresses normal bone marrow function. 1
• Myelodysplastic syndromes, causing ineffective production of multiple cell lines. 1
• Lymphomas and solid tumors with bone marrow metastases. 2

Nutritional Deficiencies

Vitamin B12 and folate deficiencies impair DNA synthesis, affecting rapidly dividing cells including WBC precursors. 1 While iron deficiency primarily affects RBC production, severe cases can also impact WBC production. 1

Autoimmune and Systemic Diseases

• Systemic lupus erythematosus (SLE) causes autoimmune-mediated leukopenia. 1
• Inflammatory bowel disease can cause leukopenia through multiple mechanisms. 1
• COVID-19 has been associated with decreased WBC counts through multiple pathways. 1
• Chronic kidney disease affects multiple hematologic parameters and can lead to leukopenia. 1

Increased Destruction or Sequestration

Hypersplenism causes sequestration and destruction of WBCs in an enlarged spleen. 1 This occurs in:

• Chronic liver disease with portal hypertension. 1
• Various conditions causing splenomegaly. 1

Infections

Certain infections can cause leukopenia through increased utilization and destruction of white blood cells, particularly severe bacterial infections and some viral infections. 5, 6

Diagnostic Approach

When evaluating low WBC count, first distinguish between decreased production versus increased destruction/sequestration. 1

• Review all medications for potential bone marrow suppressants—this is a potentially reversible cause that should be identified early. 1
• Check nutritional markers: iron studies, vitamin B12, and folate levels. 1
• Assess for autoimmune conditions if clinically indicated (autoimmune markers). 1
• Evaluate for splenomegaly through physical examination and imaging if hypersplenism is suspected. 1
• Consider bone marrow evaluation if the cause remains unclear after initial workup. 1

Critical Clinical Pearls

The major danger of neutropenia is the risk of serious infection, requiring prompt identification of the cause and effective antimicrobial therapy when systemic infection is present. 5, 6

• In cancer patients, the pathogenesis is often multifactorial, including direct marrow infiltration, treatment effects, and nutritional factors. 1
• Patients with elevated blast counts are at higher risk for tumor lysis and organ dysfunction secondary to leukostasis, requiring measures to rapidly reduce WBC count such as apheresis or hydroxyurea. 2
• Always consider medication effects as potentially reversible causes before pursuing extensive workup. 1