What are the causes of leukocytosis?

Causes of Leukocytosis

Leukocytosis is most commonly caused by infections and inflammatory processes, but can also result from primary bone marrow disorders, physiological stress, medications, and various other conditions. 1, 2

Infectious Causes

• Bacterial infections - most common infectious cause, particularly associated with neutrophilia 1
• Viral infections - often associated with lymphocytosis, especially in children 3
• Parasitic infections - typically associated with eosinophilia 1
• Fungal infections - can cause various patterns of leukocytosis 4

Inflammatory and Autoimmune Causes

• Adult-onset Still's disease - characterized by striking neutrophilia with WBC counts often >15,000 cells/μL 1
• Kawasaki disease - common in children, presents with elevated WBC count 4
• Chronic inflammatory conditions - including rheumatoid arthritis, inflammatory bowel disease 3
• Tissue necrosis - from burns, myocardial infarction, or pancreatitis 2

Hematologic Malignancies

• Acute leukemias - including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) 4
• Chronic leukemias - including chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) 4
• Myeloproliferative disorders - such as polycythemia vera, essential thrombocythemia 4
• Lymphoproliferative disorders - including lymphomas 4

Physiological and Stress-Related Causes

• Physical stress - from seizures, trauma, surgery, or overexertion 2
• Emotional stress - can elevate white blood cell counts 2
• Pregnancy - physiological leukocytosis, especially in the third trimester 5
• Exercise - transient leukocytosis 3

Medication-Induced Causes

• Corticosteroids - cause demargination of neutrophils 2
• Lithium - increases neutrophil production 2
• Beta agonists - cause demargination of neutrophils 2
• Growth factors - such as G-CSF and GM-CSF 3

Other Causes

• Splenectomy or asplenia - due to loss of splenic sequestration of leukocytes 3
• Smoking - associated with chronic elevation of WBC count 3
• Obesity - associated with chronic low-grade inflammation 3
• Hemophagocytic lymphohistiocytosis - rare but severe cause of leukocytosis 4

Warning Signs of Serious Causes

• WBC counts above 100,000/μL represent a medical emergency due to risk of brain infarction and hemorrhage 2
• Concurrent abnormalities in red blood cell or platelet counts suggest primary bone marrow disorders 2
• Constitutional symptoms (fever, weight loss, night sweats) suggest malignancy 6
• Hepatosplenomegaly, lymphadenopathy, or unexplained bleeding/bruising raise suspicion for hematologic malignancy 4

Diagnostic Approach

1. Determine which WBC subpopulation is increased - neutrophilia, lymphocytosis, monocytosis, eosinophilia, or basophilia 1
2. Review peripheral blood smear - for immature cells, abnormal morphology, and blasts 1
3. Consider patient's age and pregnancy status - use appropriate reference ranges 3
4. Evaluate for signs and symptoms of infection - most common cause of leukocytosis 3
5. Review medication list - for potential drug-induced causes 2

When evaluating leukocytosis, it's essential to distinguish between reactive causes and primary bone marrow disorders, as the management approach and prognosis differ significantly. Extremely elevated counts, abnormal cell morphology, or accompanying cytopenias should prompt urgent hematology consultation.