What are the possible causes of an absolute neutrophil count of 13,460 cells/µL?

Causes of Elevated Absolute Neutrophil Count (13,460 cells/µL)

An absolute neutrophil count of 13,460 cells/µL represents moderate neutrophilia (leukocytosis) and most commonly indicates acute bacterial infection, systemic inflammation, physiologic stress response, or medication effect—not a primary hematologic disorder. 1, 2

Primary Infectious Causes

• Acute bacterial infection is the most common cause of neutrophilia in this range, particularly gram-positive organisms (Staphylococcus aureus, Streptococcus species) and gram-negative pathogens (E. coli, Klebsiella, Pseudomonas aeruginosa). 1

• Severe fungal infections (especially invasive aspergillosis or candidiasis) can produce marked neutrophilia when the immune system is responding appropriately. 1

• Viral infections occasionally trigger neutrophilia through secondary bacterial superinfection or cytokine-mediated bone marrow stimulation. 1

Inflammatory & Stress-Related Causes

• Systemic inflammatory response syndrome (SIRS) from any cause—including sepsis, trauma, burns, or major surgery—drives neutrophil release from bone marrow reserves. 1, 2

• Tissue necrosis from myocardial infarction, pulmonary embolism, or tumor necrosis produces inflammatory cytokines that mobilize neutrophils. 2

• Acute hemorrhage or hemolysis triggers compensatory neutrophilia as part of the stress response. 2

Medication & Treatment-Related Causes

• Granulocyte colony-stimulating factor (G-CSF) administration (filgrastim, pegfilgrastim) is a common iatrogenic cause in oncology patients, often producing ANC >10,000 cells/µL. 3

• Corticosteroids (prednisone, dexamethasone, methylprednisolone) cause neutrophilia by demarginating neutrophils from vessel walls and delaying apoptosis. 2

• Lithium therapy chronically elevates neutrophil counts through direct bone marrow stimulation. 2

• Epinephrine and other catecholamines acutely mobilize marginated neutrophils during physiologic stress. 2

Hematologic & Malignant Causes

• Chronic myeloid leukemia (CML) presents with marked leukocytosis (often >25,000 cells/µL) but should be considered when neutrophilia persists without clear infectious or inflammatory cause; look for basophilia, eosinophilia, and left shift on differential. 1, 2

• Myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, primary myelofibrosis) can produce persistent neutrophilia alongside other cytopenias or cytoses. 2

• Leukemoid reaction (ANC >50,000 cells/µL with left shift mimicking leukemia) occurs with severe infection, malignancy, or hemolysis but is distinguished from CML by absence of basophilia and presence of toxic granulation. 2

• Solid tumors (lung, gastric, renal cell carcinoma) occasionally produce granulocyte colony-stimulating factors as paraneoplastic phenomena. 2

Congenital & Chronic Disorders

• Leukocyte adhesion deficiency (LAD) presents with persistent marked leukocytosis (often >20,000 cells/µL) even without infection, due to impaired neutrophil migration into tissues; suspect when recurrent severe bacterial/fungal infections occur despite high ANC. 1

• Chronic idiopathic neutrophilia is a diagnosis of exclusion after ruling out secondary causes; typically ANC remains 8,000–15,000 cells/µL without progression. 2

• Hereditary neutrophilia is rare and familial; documented stable elevation over years without complications. 2

Diagnostic Approach

• Review the peripheral blood smear manually to assess for left shift (bands >10%, metamyelocytes, myelocytes), toxic granulation, Döhle bodies (suggesting bacterial infection), basophilia/eosinophilia (suggesting CML), or circulating blasts (suggesting acute leukemia). 1, 4, 2

• Obtain inflammatory markers: CRP and ESR are elevated in infection and inflammation but normal in medication-induced or congenital neutrophilia. 4

• Check medication history for G-CSF, corticosteroids, lithium, or recent epinephrine administration. 3, 2

• Assess clinical context: fever, localizing infection symptoms, recent surgery/trauma, known malignancy, or chronic inflammatory disease. 1

• If neutrophilia persists >2 weeks without clear cause, obtain bone marrow biopsy with cytogenetics and BCR-ABL1 testing to exclude CML or other myeloproliferative neoplasm. 2

Critical Pitfalls to Avoid

• Do not assume neutrophilia always indicates infection; medication effect (especially G-CSF or corticosteroids) is equally common in hospitalized patients. 3, 2

• Do not overlook leukocyte adhesion deficiency in patients with recurrent severe infections despite persistently elevated ANC; this diagnosis requires functional neutrophil testing. 1

• Do not delay BCR-ABL1 testing when neutrophilia is accompanied by basophilia, splenomegaly, or unexplained thrombocytosis, as early CML diagnosis impacts treatment outcomes. 2

• Do not interpret automated differential alone; manual review is essential to detect left shift, toxic changes, or immature cells that guide diagnosis. 4, 2