Considerations of HLA, Renal Failure, Valproic Acid Use, andCurrent Treatment Guidelines in Clozapine-Induced Agranulocytosis

Clozapine, the choice atypical antipsychotic for refractory schizophrenia, schizoaffective disorder, and bipolar disorder, has beenshown to reduce positive and negative symptoms of schizophrenia. Clozapine, though beneficial in reducing the need forhospitalization, rehabilitation, and health care costs, is known as a drug of last resort due to its potential adverse event ofclozapine-induced agranulocytosis, which holds a case fatality rate between 4.2 and 16%. Herein, we describe a female patientwith longstanding schizoaffective disorder and chronic kidney disease who suffered from clozapine-induced agranulocytosisafter failing two other atypical antipsychotics. Retrospective considerations of this case and management highlight risk factorssuch as HLA status, renal failure, and concurrent valproic acid use which presently do not have official screening, guidelines, orrestrictions in place when prescribing clozapine. Additionally, there are no specific clozapine-induced agranulocytosismanagement recommendations such as G-CSF/filgrastim dose, timing of bone marrow aspirate and biopsy, and use ofconcomitant valproate. We propose that further comprehensive official screening, monitoring, and guidelines in the prescribingof clozapine, and further guidelines in the treatment of clozapine induced agranulocytosis, could increase the cost-effectivenessof clozapine treatment, and decrease the incidence, and morbidity of this feared adverse event