Agranulocytosis

Agranulocytosis is a severe form of neutropenia characterized by a marked reduction or complete absence of granulocytes, especially neutrophils, in the peripheral blood.

• Definition:
  • Absolute neutrophil count (ANC) < 500/μL (0.5 × 10⁹/L)
  • In agranulocytosis, ANC is often < 100/μL or even zero
  • Other granulocytes (eosinophils, basophils) are also typically very low or absent
• Clinical Consequences:
  • Profound immunosuppression → high risk of serious, life-threatening infections
  • Common manifestations:
    • Fever
    • Sore throat
    • Oral ulcers
    • Sepsis without localizing signs
• Causes:
  • Drug-induced (most common)
    • Clozapine, carbimazole, methimazole, PTU
    • Sulfonamides, chloramphenicol, dapsone
    • Chemotherapy
  • Autoimmune diseases
    • Lupus
    • Rheumatoid arthritis
  • Bone marrow failure syndromes
    • Aplastic anemia
    • Myelodysplastic syndromes
  • Infections
    • EBV
    • HIV
    • Hepatitis
    • Parvovirus
  • Congenital
    • Kostmann syndrome
• Pathogenesis:
  • Immune-mediated
  • Direct toxic mechanisms leading to destruction or suppression of neutrophil precursors
• Diagnosis:
  • CBC with differential: severe neutropenia
  • Bone marrow biopsy: may show granulocytic hypoplasia or aplasia
  • Investigate for:
    • Recent drug exposures
    • Infections
    • Autoimmune markers
• Treatment:
  • Stop offending drug immediately (if drug-induced)
  • Empiric broad-spectrum antibiotics if febrile
  • Consider G-CSF (filgrastim) to speed neutrophil recovery
  • Protective isolation in severe cases
  • Treat underlying cause

History of the term