What are the causes of leukocytosis with neutrophilia?

Causes of Leukocytosis with Neutrophilia (WBC 14, Neutrophils 10.6)

Bacterial infection is the most common cause of neutrophilic leukocytosis, particularly when accompanied by a left shift, with common pathogens including Staphylococcus aureus, E. coli, and coagulase-negative staphylococci. 1

Infectious Causes (Most Common)

• Bacterial infections are the primary etiology, with an elevated total band count >1500 cells/mm³ having a high likelihood ratio for documented bacterial infection 1
• Septicemia frequently presents with high-grade leukocytosis and left shift, and WBC counts >20,000 cells/mm³ are associated with increased mortality in bloodstream infections 1
• The severity of infection correlates with specific markers: neutrophil percentage >90% has a likelihood ratio of 7.5 for bacterial infection, while band neutrophils >16% have a likelihood ratio of 4.7 1

Non-Infectious Inflammatory Causes

• Systemic inflammatory disorders including vasculitis and connective tissue diseases can produce neutrophilic leukocytosis 1
• Adult-onset Still's disease causes striking neutrophilia, with 50% of patients having counts >15,000 cells/L and 37% exceeding 20,000 cells/L 1
• Malignancy, particularly solid tumors that are necrotic or causing obstruction, can trigger neutrophilic leukocytosis 1

Acute Physiologic Stressors

• The peripheral WBC count can double within hours due to demargination from large bone marrow storage pools 2
• Acute stressors include surgery, exercise, trauma, and emotional stress 2

Medication and Chronic Conditions

• Certain medications, particularly corticosteroids, can cause neutrophilia 2
• Chronic conditions associated with leukocytosis include asplenia, smoking, obesity, and chronic inflammatory states 2

Thrombotic Conditions

• Heparin-induced thrombocytopenia (HIT) commonly causes leukocytosis and neutrophilia, particularly in patients with HIT-associated thrombosis 3
• Persistent neutrophilia ≥9.0 × 10⁹/L is independently associated with doubled VTE risk (OR 2.0), and counts ≥10.0 × 10⁹/L carry even higher risk (OR 2.3) 4

Critical Clinical Pitfalls

• Do not assume infection is absent based on the degree of leukocytosis alone—focus on clinical context, fever, and other inflammatory markers 5
• In neutropenic patients recovering from severe neutropenia (<500 cells/mm³), reactive leukocytosis may occur, especially with concurrent infection 1
• Leukocytosis/neutrophilia in heparin-exposed patients should not automatically suggest infection—consider HIT-associated thrombosis 3

Diagnostic Approach for This Patient

With WBC 14 and neutrophils 10.6 (moderate elevation):

• Search for bacterial infection first: look for fever, localizing symptoms, elevated bands, toxic granulations on peripheral smear 1
• Assess for acute stressors: recent surgery, trauma, severe emotional stress 2
• Review medication list for corticosteroids or other causative agents 2
• Consider inflammatory conditions if infection is excluded, particularly if constitutional symptoms (fever, weight loss) are present 1, 2
• If heparin exposure exists and thrombocytopenia is present, evaluate for HIT 3