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Clozapine-induced thrombocytosis

Published online by Cambridge University Press:  02 January 2018

M. E. Hampson*
Affiliation:
Rosebery House, Waterford Street, Old Basford, Nottingham NG6 0HG
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Abstract

Type
Columns
Copyright
Copyright © 2000 The Royal College of Psychiatrists 

Clozapine is known to cause blood dyscrasias, typically neutropenia and agranulocytosis. A raised platelet count, with clozapine as the sole implicated agent, had been reported to the Committee on Safety of Medicines in three cases. This is the first to be published.

A middle-aged male with ICD schizophrenia failed to respond to neuroleptic medication (haloperidol 25 mg/day, chlorpromazine 500 mg/day), or olanzapine at a dose of 20 mg/day for six weeks. He was therefore started on clozapine. He continued to receive droperidol 20 mg/day and zopiclone 7.5 mg nocte.

Fifteen days after commencing clozapine he complained of nausea. His clozapine was increased the next day by 25 mg to 300 mg/day. He complained of arthralgia and became hypotensive (b.p. 90/60 mmHg). Clozapine was stopped and the symptoms subsided over 36 hours. Clozapine was then restarted at a dose of 100 mg twice daily. He re-developed hypotension, arthralgia, malaise and sweating after one dose. He was apyrexial. Five days after the onset of nausea, the platelet count was 454 × 109/l (normal range: 150-450 × 109/l), the erythrocyte sedimentation rate (ESR) 70 mm/h and the C-reactive protein 103. Eight days later the ESR had fallen to < 5 mm/h but the platelet count had risen to 774 × 109/l. Five days later the platelet count had fallen to 393 × 109/l and subsequently returned to normal.

Muller et al (Reference Muller, Manns and Hammes1991) reported fever 7-15 days after commencing clozapine in 12 patients with non-specific inflammatory parameters, including a raised white cell count, ESR and C-reactive protein. They did not comment on platelet changes. This case has similar symptoms but without pyrexia. The rapid re-emergence of symptoms on re-challenge suggests an immune response to the drug, and both thrombocytosis and thrombocytopenia are recognised features of such a reaction.

References

Muller, H., Manns, M., Hammes, E., et al (1991) Studies on inflammatory side effects of clozapine. Biological Psychiatry, 29 (suppl.) 415S416S.Google Scholar
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