Neutropenia

Background

• Low concentration of circulating neutrophils

ANC	Classification
≥1500	Normal
1000-1499	Mild
500-999	Moderate
<500	Severe
0	Agranulocytosis

Etiologies

Congenital

• Constitutional neutropenia: mild (ANC>1000), chronic
• Benign ethnic neutropenia: mild (ANC>1000), chronic, usually in patients with Mediterranean or African ancestry
• Benign familial neutropenia: same as above, but hereditary and not associated with a specific ethnicity
• Cyclic neutropenia: hereditary, with severe neutropenia on a 21-day cycle since childhood
• Others: severe congenital neutropenia, Schwachman-Diamond syndrome, Fanconi anemia, dyskeratosis congenita, Chediak-Higash syndrome, myelokathesis, Griscelli syndrome II, and cartilage-hair hypoplasia

Acquired

• Infectious
  • Active infection, particularly viral, but including severe sepsis from any cause; more common in the elderly
  • Post-infectious neutropenia, most commonly in children after viral infections (particularly varicella, measles, rubella, influenza, hepatitis, EBV, or HIV)
    • EBV and HIV can sometimes cause prolonged neutropenia; the rest are self-limited
  • Bacterial infections, including Brucella, Rickettsiae, and mycobacteria
• Drug-induced neutropenia, including agranulocytosis or more mild neutropenia
• Autoimmune
  • Primary: typically in patients less than 1 year old, can be severe, but usually resolves within 2 years
    • Needs prophylactic antibiotics and GCSF
  • Secondary: usually mild, in the context of a systemic autoimmune disease (with lupus being common and tends to reflect disease activity)
  • Felty syndrome (triad of rheumatoid arthritis, splenomegaly, and neutropenia)
• Malignancy
  • Acute leukemia
  • Myelodysplastic syndrome
  • LGL leukemia: associated with rheumatoid arthritis and can present as a Felty syndrome
  • Myeloma
  • Lymphoma
  • Myelophthisic process
• Dietary
  • Vitamin B12 deficiency
  • Folate deficiency
  • Copper deficiency
  • Global caloric malnutrition, including anorexia nervosa
• Chronic idiopathic neutropenia

Further Reading

• How we evaluate and treat neutropenia in adults. Blood 2014; 124 (8): 1251–1258. doi: https://doi.org/10.1182/blood-2014-02-482612