Causes of Leukocytosis
Leukocytosis is most commonly caused by infections or inflammatory processes, but can also result from physiologic stress, medications, or primary bone marrow disorders requiring different management approaches depending on the underlying etiology and severity.
Definition and Classification
- Leukocytosis: White blood cell (WBC) count >11,000/μL in non-pregnant adults 1
- Severity classification 2:
- Mild: 1,000-1,500/μL
- Moderate: 500-1,000/μL
- Severe: <500/μL (requires urgent attention)
- Critical: >100,000/μL (medical emergency due to risk of brain infarction and hemorrhage) 1
Common Causes of Leukocytosis
1. Infections
- Bacterial infections (most common cause)
- Viral infections
- Fungal infections
- Parasitic infections
2. Inflammatory Conditions
- Autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus)
- Tissue damage/necrosis
- Vasculitis
- Adult-onset Still's disease (characterized by striking neutrophilia with peripheral WBC counts often >15,000 cells/μL, with some patients having counts >20,000) 3
3. Physiologic Stress
- Physical stress (seizures, anesthesia, overexertion)
- Emotional stress
- Pregnancy
- Post-surgical states
4. Medication-Induced
- Corticosteroids
- Lithium
- Beta-agonists
- Epinephrine
- G-CSF (filgrastim)
- Certain antibiotics
5. Primary Bone Marrow Disorders
- Acute leukemias
- Acute myeloid leukemia (AML)
- Acute lymphoblastic leukemia (ALL)
- Chronic leukemias
- Chronic myeloid leukemia (CML)
- Chronic lymphocytic leukemia (CLL)
- Myeloproliferative disorders
- Polycythemia vera
- Essential thrombocythemia
- Primary myelofibrosis
6. Other Causes
- Splenectomy or hyposplenism
- Hemolysis
- Smoking
- Tissue injury
- Malignancy (solid tumors)
- Kawasaki disease (in children) 3
Red Flags for Primary Bone Marrow Disorders
- Extremely elevated WBC counts (especially >50,000/μL)
- Concurrent abnormalities in red blood cell or platelet counts
- Weight loss, night sweats, or fever
- Bleeding or bruising
- Hepatosplenomegaly or lymphadenopathy
- Immunosuppression 1, 4
Evaluation of Leukocytosis
Initial Assessment
Determine which WBC subpopulation is increased:
- Neutrophilia (most common)
- Lymphocytosis
- Monocytosis
- Eosinophilia
- Basophilia
Review peripheral blood smear for:
- Presence of immature cells ("left shift")
- Abnormal cell morphology
- Blasts (suggestive of acute leukemia)
Assess for associated symptoms:
- Fever, chills (infection)
- Joint pain, rash (inflammatory conditions)
- Constitutional symptoms (weight loss, night sweats, fatigue)
Additional Testing Based on Clinical Suspicion
- Complete blood count with differential
- Blood cultures (if infection suspected)
- Inflammatory markers (ESR, CRP)
- Bone marrow aspiration/biopsy (if primary bone marrow disorder suspected)
- Imaging studies as indicated
- Specialized molecular testing for leukemia diagnosis
Management Approach
Emergency Management
- WBC counts >100,000/μL require immediate intervention due to risk of leukostasis 1
- In CML with symptomatic leukocytosis: hydroxyurea, apheresis, imatinib, or clinical trial 3
- In acute leukemia: prompt referral to hematology and consideration of induction chemotherapy 3
Infection-Related Leukocytosis
- Identify and treat the underlying infection
- Appropriate antimicrobial therapy based on suspected source
Medication-Induced Leukocytosis
- Consider dose reduction or discontinuation of offending medication if clinically appropriate 2
Inflammatory Condition-Related Leukocytosis
- Treat the underlying inflammatory condition
- Anti-inflammatory medications as appropriate
Primary Bone Marrow Disorders
- Acute leukemia: Induction chemotherapy with cytarabine and anthracycline 3, 2
- CML: Tyrosine kinase inhibitors (e.g., imatinib) 2
- CLL: Treatment decisions based on disease stage and genetic factors 3, 2
Special Considerations
- "Unexplained" leukocytosis in hospitalized patients may represent persistent inflammation-immunosuppression and catabolism syndrome (PICS) rather than ongoing infection 5
- Excessive antibiotic use in patients with non-infectious leukocytosis should be avoided
- Leukocytosis with eosinophilia (>500 cells/μL) may indicate allergic reactions, parasitic infections, or certain malignancies 5
Remember that while leukocytosis is often a response to infection or inflammation, persistent or severe leukocytosis without obvious cause warrants thorough investigation to rule out primary bone marrow disorders.