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

Abstract

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.

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine

“…135 However, some cases of late-onset clozapine-induced agranulocytosis have been reported. 136,137 The development of agranulocytosis may be independent of dosage and risk factors include older age, female sex, human leukocyte antigen haplotypes and concomitant treatment with other drugs known to cause agranulocytosis. 52,[138][139][140][141][142] Interestingly, in cases with severe clozapine-induced agranulocytosis, the occurrence did not depend on the clozapine dosage.…”

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

“…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.…”

Neutropenia with Multiple Antipsychotics Including Dose Dependent Neutropenia with Lurasidone

“…Although in one case report, a patient developed agranulocytosis with four antispychotic medications (olanzapine, quetiapine, risperidone and aripiprazole) 8) and in another with three antipsychotics (quetiapine, olanzapine, and aripiprazole), 9) patients were able to be successfully switched to a different antipsychotic medication. Immunological mechanisms 10) are likely important in patients who develop repeated episodes of neutropenia. Dose related component has been reported for clozapine.…”