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/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

Serious disease in an affected individual

Represents a significant burden to health care

Early detection decreases risk

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

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

Advantages of monitoring system

Early detection prior to symptomsStop the drug earlyEarly initiation of treatment and management of agranulocytosisReassurance to patient, family and health care providers

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