In which conditions are neutrophil counts increased and decreased?

Conditions Associated with Neutrophil Count Changes

Neutropenia (Decreased Neutrophils)

Neutropenia is defined as an absolute neutrophil count (ANC) below 1,500 cells/µL, with infection risk rising markedly when counts fall below 1,000 cells/µL and becoming severe below 500 cells/µL. 1, 2

Medication-Induced Causes

• Chemotherapy is the most common cause of neutropenia, with risk proportional to dose intensity and duration of treatment 3
• Thiopurine agents (azathioprine, mercaptopurine) cause dose-dependent myelosuppression and should be withheld when ANC falls below 2.0 × 10⁹/L 4
• Clozapine therapy requires immediate discontinuation if ANC drops to 1.0–1.5 × 10⁹/L 4
• Other medications including antiepileptics and certain antibiotics can induce neutropenia 4

Malignancy-Related Causes

• Hairy cell leukemia presents with profound monocytopenia and neutropenia (ANC < 0.5 × 10⁹/L in 39% of cases) 4
• Myelodysplastic syndromes cause neutropenia with dysplastic peripheral blood findings 4
• Acute leukemia during induction or consolidation therapy produces prolonged neutropenia 1
• Lymphoid malignancies can cause hypogammaglobulinemia and secondary neutropenia 3

Immunologic and Infectious Causes

• Autoimmune neutropenia is identified by anti-neutrophil antibodies 5, 6
• HIV infection increases risk of neutropenia, particularly with low CD4 counts 3
• COVID-19 infection causes leukopenia, neutropenia, and lymphopenia in PCR-positive patients 7

Inherited Bone Marrow Failure Syndromes

• Severe congenital neutropenia (SCN) presents with persistent neutropenia without cyclic patterns 5, 6
• Cyclic neutropenia demonstrates regular 21-day cycles of neutrophil nadirs 6
• Shwachman-Diamond syndrome and Fanconi anemia can manifest with neutropenia and additional systemic features 6, 4

Nutritional Deficiencies

• Vitamin B12 or folate deficiency causes macrocytic anemia with possible neutropenia 4
• Copper deficiency produces neutropenia and anemia 4

Neutrophilia (Increased Neutrophils)

Neutrophilia represents an elevated neutrophil count, typically defined as ANC above 7,500–8,000 cells/µL, and reflects either reactive processes or primary hematologic disorders.

Infection and Inflammation

• Bacterial infections, particularly sepsis and septic shock, cause marked neutrophilia with left shift 2, 8
• Viral infections can produce neutrophilia, though lymphopenia is more characteristic 7
• Systemic inflammation from any cause triggers neutrophil release from bone marrow 8

Surgical Stress and Trauma

• Major surgery produces marked neutrophilia (up to 84.4%) with concurrent lymphopenia (down to 10.3%) within 24 hours postoperatively 8
• Multiple trauma and shock states cause rapid neutrophil mobilization 8
• The severity of neutrophilia correlates with surgical stress intensity (SOFA and APACHE II scores) 8

Hematologic Malignancies

• Chronic myelomonocytic leukemia typically shows monocytosis (>1.0 × 10⁹/L) but can present with neutrophilia 4
• Myeloproliferative neoplasms cause marked neutrophilia, often with accompanying thrombocytosis 4
• T-cell large granular lymphocytic leukemia paradoxically causes neutropenia rather than neutrophilia 9

Medication and Treatment Effects

• Colony-stimulating factors (G-CSF, filgrastim) administered at 5 µg/kg/day increase neutrophil counts therapeutically 5, 4
• Corticosteroid therapy causes neutrophilia by demargination of neutrophils 8

Psychiatric and Stress-Related Causes

• Major depression is associated with absolute neutrophilia and leukocytosis, particularly in medication-treated patients 10
• Psychosocial stress can alter white blood cell distribution, though effects are variable 10

Clinical Significance and Risk Stratification

The frequency and severity of infection are inversely proportional to neutrophil count, with risks of severe infection and bloodstream infection greatest (10–20%) at counts below 100 cells/µL. 3

• Severe neutropenia (ANC < 0.5 × 10⁹/L) in chemotherapy patients with septic shock is associated with significantly worse survival (median 13 days versus 106 days) and hazard ratios of 1.56–2.03 11
• Fever defined as temperature >38.3°C or >38.0°C for ≥1 hour warrants urgent evaluation regardless of neutrophil count 1, 2, 4
• The neutrophil-to-lymphocyte ratio (NLR) serves as a rapid marker of systemic inflammation severity, with elevated NLR correlating with worse clinical outcomes 7, 8