Late-Onset Agranulocytosis in a Patient With Schizophrenia After 17 Months of Clozapine Treatment

Bhanji, Nadeem H.; Margolese, Howard C.; Chouinard, Guy; Turnier, Luc

doi:10.1097/01.jcp.0000088917.02635.7a

Cited by 17 publications

(8 citation statements)

References 6 publications

(1 reference statement)

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“…The report of clozapine-induced late leukopenia by Latif et al [1] adds to the body of literature on this rare but important subject [2][3][4][5]. We would like to comment on this case report and draw attention to the differences between guidelines on this subject.…”

mentioning

confidence: 78%

Clozapine-induced leukopenia: arguments for rechallenge

Bogers

Cohen

Schulte³

et al. 2011

Ir J Med Sci

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mentioning

confidence: 78%

Clozapine-induced leukopenia: arguments for rechallenge

Bogers

Cohen

Schulte³

et al. 2011

Ir J Med Sci

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“…2 Over 90% of our cases developed agranulocytosis within the first three months of drug treatment, with half of the cases having exposed to the drug for more than one month. However, there were few reports of late onset of agranulocytosis after prolonged treatment of clozapine 30,31 and antithyroid drugs. 32 In our study, we also found one case with delayed onset after three years of clozapine treatment.…”

Section: Discussionmentioning

confidence: 99%

Incidence and risk estimate of drug‐induced agranulocytosis in Hong Kong Chinese. A population‐based case–control study

Sing

Wong

Cheung

et al. 2017

Pharmacoepidemiology and Drug

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Purpose Drug‐induced agranulocytosis is a rare but life‐threatening adverse drug reaction. Its epidemiology in Chinese is largely unknown. This study aimed to estimate the incidence, mortality, and risk of the drugs associated with agranulocytosis in Hong Kong Chinese. Methods A population‐based case–control study was conducted using the Clinical Data Analysis and Reporting System, a database managed by the Hong Kong Hospital Authority. Patients with drug‐induced agranulocytosis from 1 January 2004 to 31 December 2013 were identified. World Health Organization causality assessment was used to evaluate the possible drug aetiology of each case. Odd ratios (ORs) of the drug exposure were calculated using exact conditional logistic regression. Results A total of 155 cases of drug‐induced agranulocytosis were identified. Mean age was 51.4 years, and 95 cases were female. Incidence rate was estimated to be 2.2 cases per million person‐years, and the all‐cause mortality of patients with drug‐induced agranulocytosis was 3.9%. Among the cases, the most common associated drug groups were antithyroid drugs (41.9%), antimicrobials (20%), anticonvulsants (10.3%), and antipsychotics (6.5%). Carbimazole had the highest risk of agranulocytosis (adjusted OR 416.7, 95% confidence interval (CI) 51.5–3372.9) with an incidence of 9.2 (95%CI 6.9–12.1) per 10 000 users and 3.6 (95%CI 2.7–4.8) per 10 000 user‐years. Other drugs with significant risk included cephalosporins, clozapine, penicillins, phenytoin, and propyl thiouracil. Conclusions The incidence and mortality in Hong Kong Chinese were relatively low compared to Caucasians. Antithyroid drugs were the most common implicated drug class, and carbimazole had the highest risk of agranulocytosis. Copyright © 2017 John Wiley & Sons, Ltd.

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“…We searched the PubMed search engine and available data suggests that there is limited literature in the form of case reports of late onset neutropenia and late onset agranulocytosis associated with clozapine, 4 – 17) with one of the reports showing the association after 19 years of use of clozapine. 5) In a review of literature, authors reported 16 case reports available prior to 2012.…”

Section: Discussionmentioning

confidence: 99%

“… 3) However, there are few reports of late onset neutropenia with clozapine after as long as 19 years of use of clozapine. 4 – 17) Studies have attempted to find out the factors associated with clozapine induced neutropenia. Among the various factors reported to be associated with clozapine induced neutropenia, there is some data to suggest that genetic vulnerability in the form of variations in the human leukocyte-antigen haplotypes predisposes a person to develop neutropenia.…”

Section: Introductionmentioning

confidence: 99%

Late Onset Agranulocytosis with Clozapine Associated with HLA DR4 Responding to Treatment with Granulocyte Colony-stimulating Factor: A Case Report and Review of Literature

Singh

Grover

Malhotra

et al. 2016

Clin Psychopharmacol Neurosci

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Agranulocytosis as a side effect of clozapine has been reported to be associated with initial phases of treatment, i.e., first six months. Agranulocytosis with clozapine during the initial phases of treatment has been linked to genetic vulnerability in the form of variations in the human leukocyte-antigen haplotypes. However, there is limited literature on late onset agranulocytosis with clozapine and this has very rarely been linked to human leukocyte-antigen haplotypes vulnerability. In this report we review the existing data on late onset agranulocytosis with clozapine and describe the case of a young man, who developed agranulocytosis with clozapine after 35 months of treatment and was found to have genetic vulnerability in form of being positive for HLA DR4. This case highlights underlying autoimmune immune mechanism in clozapine-induced agranulocytosis and the need for frequent blood count monitoring on clozapine even after the initial 6 months of starting treatment especially in patients with genetic vulnerability to develop this condition.

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Late-Onset Agranulocytosis in a Patient With Schizophrenia After 17 Months of Clozapine Treatment

Cited by 17 publications

References 6 publications

Clozapine-induced leukopenia: arguments for rechallenge

Clozapine-induced leukopenia: arguments for rechallenge

Incidence and risk estimate of drug‐induced agranulocytosis in Hong Kong Chinese. A population‐based case–control study

Late Onset Agranulocytosis with Clozapine Associated with HLA DR4 Responding to Treatment with Granulocyte Colony-stimulating Factor: A Case Report and Review of Literature

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