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Overview of Agranulocytosis. Stan Gerson, MD Chief, Division of Hematology & Oncology Asa & Patricia Shiverick Professor of Hematological Oncology University Hospitals of Cleveland, Case Western Reserve University. Agranulocytosis. Drop in neutrophil count to less than 500/mm 3

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overview of agranulocytosis

Overview of Agranulocytosis

Stan Gerson, MD

Chief, Division of Hematology & Oncology

Asa & Patricia Shiverick Professor of Hematological Oncology

University Hospitals of Cleveland,

Case Western Reserve University

agranulocytosis
Agranulocytosis
  • Drop in neutrophil count to less than 500/mm3
  • High incidence of neutropenic fever [>80%]
  • Duration of agranulocytosis directly impacts its severity and morbidity [fever in 100% of patients after 5 days]
  • Mortality is related to infections and their sequella
  • Rare in the absence of a serious illness or drug administration
clozaril associated agranulocytosis
Clozaril® associated agranulocytosis
  • Serious disease in an affected individual
  • Represents a significant burden to health care
  • Early detection decreases risk
key features of clozapine associated agranulocytosis
Key features of clozapine associated agranulocytosis
  • Onset in 1-3 weeks - detected by monitoring
    • Rapid onset is more severe
    • Benefit from early detection, drug is stopped prior to onset of symptoms
  • Often the drug is stopped with a WBC of 2000-3000 and an ANC of 300-1000
  • Unique features
    • Severe drop in granulocyte count [to 0] even after the drug is stopped
    • Prolonged duration [8d with growth factors, 15 d without]
    • Significant risk of neutropenic fever, severe internal infection
management of agranulocytosis
Management of agranulocytosis
  • Hospitalization of patient is recommended
  • Daily observation for fever, infection; culture and image of possible sites of infection
  • Antibiotics - either prophylactic or for fever
  • Hematopoietic growth factors [G-CSF, GM-CSF]
  • Duration of illness - 8-25 days
  • Substantial cost for treatment: hospitalization, antibiotics and growth factors
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Advantages of monitoring system

  • Early detection prior to symptoms
  • Stop the drug early
  • Early initiation of treatment and management of agranulocytosis
  • Reassurance to patient, family and health care providers
conclusions
Conclusions
  • Clozaril associated agranulocytosis is a serious illness
  • Monitoring allows detection prior to illness
  • Early detection can limit morbidity by prompt institution of management
  • Management is costly