Vascular events associated with pharmacotherapy

Further to an article on the prevalence of vascular events in association with the treatment of psychotic illness (Thomassen et al, 2001) and the subsequent correspondence (Curtin & Blum, 2002), we would like to add our comments to this interesting topic. On our unit we have recently had occasion to observe a patient with haematological abnormalities that we feel were directly associated with treatment with antipsychotic medication. The case described below attests to the potential danger of therapy for schizophrenia and adds to concerns regarding the use of clozapine in particular.

Ms B., a 40-year-old woman, was receiving treatment with antipsychotic medication for recurrent episodes of agitation and psychosis. There had been a relatively poor response to trials of three antipsychotic agents and her side-effect profile was such that there were concerns about developing signs of tardive dyskinesia. A trial of clozapine was commenced and beneficial effects were apparent within 4 weeks.

Three months into treatment there was a deterioration in Ms B.'s physical condition and she was troubled by abdominal pain and continuing dyspepsia. She was evaluated and a series of blood tests were ordered. These were normal except for a very high erythrocyte sedimentation rate (ESR) of 90 mm/l, considerably above the normal for a woman of her age. The extent of the elevation was such that a battery of tests were used by our medical colleagues to establish a cause for this abnormality. Despite extensive medical investigations no abnormality was found. The ESR remained persistently elevated above 85 mm/l.

After 5 months on treatment Ms B. developed prominent visual hallucinatory experiences, which were new developments. As these resembled epileptiform discharges that were distressing for the patient, it was decided to discontinue the clozapine therapy completely. Within 2 weeks her ESR had fallen to 15 mm/l and it has not been found to be outside the normal range since that time.

This case suggests that clozapine can produce changes in ESR, which is a crude marker of coagulation status. The persistent change seen in the ESR in this patient could not be explained by any disease process, and it certainly points to the possibility that the clozapine was implicated in increasing her blood viscosity. As a raised ESR is associated with hypercoagulability states such as those seen in malignancies, this must be a source of concern. We are pursuing our interest in this area further.