Causes of Neutrophilic Leukocytosis
Neutrophilic leukocytosis is primarily caused by bacterial infections, but can also result from inflammation, stress, medications, and primary bone marrow disorders. An elevated total band count (>1500 cells/mm³) has the highest likelihood ratio (14.5) for detecting documented bacterial infection. 1
Infectious Causes
Bacterial infections: The most common cause of neutrophilic leukocytosis, particularly with a left shift (increased band forms). Bacterial pathogens commonly include coagulase-negative staphylococci, Staphylococcus aureus, viridans group streptococci, enterococci, Escherichia coli, Klebsiella, Enterobacter species, and Pseudomonas aeruginosa 1
Septicemia: Often associated with high-grade leukocytosis and left shift. In observational studies, leukocytosis has been associated with increased mortality among patients with bloodstream infections (WBC count >20,000 cells/mm³) 1
Localized infections: Including pneumonia, pyelonephritis, cholecystitis, and skin/soft tissue infections 2, 3
Inflammatory Causes (Non-infectious)
Systemic inflammatory disorders: Including vasculitis, connective tissue diseases, and Adult-onset Still's disease (AOSD). In AOSD, leukocytosis is the result of striking neutrophilia, with 50% of patients having peripheral leukocyte counts >15,000 cells/L and 37% having WBC counts >20,000 cells/L 1
Tissue damage: Burns, myocardial infarction, pulmonary embolism, and trauma 3
Malignancy: Solid tumors can cause neutrophilic leukocytosis, particularly when necrotic or causing obstruction 1
Stress-Related Causes
Physical stress: Including seizures, anesthesia, and overexertion 3
Emotional stress: Acute psychological stress can trigger neutrophilia 3
Medication-Induced Causes
Corticosteroids: Commonly cause neutrophilia through demargination of neutrophils 3
Lithium: Can stimulate granulopoiesis 3
Beta agonists: Can cause neutrophilia through demargination 3
Primary Bone Marrow Disorders
Chronic neutrophilic leukemia (CNL): Characterized by persistent neutrophilia with mature neutrophils, hepatosplenomegaly, high neutrophil alkaline phosphatase score, and absence of Philadelphia chromosome 4, 5
Chronic myeloid leukemia: Often diagnosed incidentally due to abnormal blood cell counts 3
Myeloproliferative disorders: Can present with leukocytosis and concurrent abnormalities in red blood cell or platelet counts 3
Acute leukemias: Patients are more likely to be ill at presentation 3
Clinical Significance and Assessment
Severity markers: An increase in the percentage of neutrophils (>90%) and band neutrophils (>16%) have likelihood ratios of 7.5 and 4.7, respectively, for bacterial infection 1
Thrombotic risk: Persistent neutrophilia (≥9.0 × 10⁹/L) is associated with twice the risk of venous thromboembolism compared to those with normal neutrophil counts 6
Medical emergency: White blood cell counts above 100,000 per mm³ represent a medical emergency due to risk of brain infarction and hemorrhage 3
Diagnostic approach: When evaluating neutrophilic leukocytosis, consider concurrent abnormalities in red blood cell or platelet counts, weight loss, bleeding/bruising, organomegaly, and immunosuppression to help distinguish between reactive causes and primary bone marrow disorders 3
Special Considerations
Neutropenic patients: When neutrophil counts recover from severe neutropenia (<500 cells/mm³), a reactive leukocytosis may occur, especially in the setting of infection 1
C-reactive protein (CRP): While CRP levels >100 mg/L suggest bacterial infection, the specificity and sensitivity for distinguishing between infectious and non-infectious causes of neutrophilic leukocytosis are only 45% and 55%, respectively 2
Functional status: In some disorders like CNL, despite elevated neutrophil counts, neutrophil function may be abnormal with reduced response to stimulation by G-CSF and GM-CSF 5