A case report of clozapine continuation after pulmonary embolism in the context of other risk factors for thromboembolism

To the Editor

Observational research and case reports indicate association of pulmonary embolism (PE) with clozapine treatment (Barbui et al., 2014). However, the aetiopathogenesis of PE among patients receiving clozapine is uncertain and is likely to be multifactorial: in many instances, modifiable risk factors such as sedation, metabolic problems and smoking could be pertinent (Paciullo, 2008). Effective therapeutic options, other than clozapine, for people with treatment-resistant schizophrenia (TRS) are limited. To our knowledge, there are only five reported cases of continuation of clozapine after PE. We report a case which highlights the possible multifactorial aetiology of PE among patients treated with clozapine and the decision to continue clozapine.

A 31-year-old woman with diagnosis of TRS with previous sub-optimal response to multiple antipsychotics and electro-convulsive therapy was initiated on clozapine. Elevated troponin and postural hypotension were observed 18 days later. Pathology tests revealed raised d-dimer (0.63 mg/L) and troponin (494 ng/L), and ventilation/perfusion scan uncovered bilateral segmental PE in lower lobes. She was commenced on enoxaparin sodium initially, which was converted to warfarin. Coagulopathy screen was negative. The haematology consultant advised that clozapine was an unlikely direct contributing factor and other risk factors such as obesity, poor mobility and ongoing active smoking were more relevant. Rapid decline of troponin levels suggested that diagnosis of myocarditis was unlikely. Clozapine treatment was continued at 300 mg without interruption, and over the next few weeks, the patient’s mental state improved significantly. Until her discharge from the psychiatry ward 3 months later, there was no further episode of thromboembolism. The haematologist advised continuation of warfarin for 6 months. The need for ongoing vigilant monitoring for further thromboembolic events and importance of managing modifiable risks was discussed with the patient.

Increased odds of developing venous thromboembolism and PE are not unique to clozapine and have been reported with other antipsychotics (Barbui et al., 2014). Although a direct thrombogenic effect of clozapine through increased platelet aggregation, reduced activated partial thromboplastin, immunomodulatory and proinflammatory effects has been proposed, features such as sedation, obesity, reduced mobility and smoking which are common among people treated with clozapine are likely to amplify the risk of PE in this population (Paciullo, 2008). While the limited therapeutic options available for TRS and modifiable risks of PE among patients treated with clozapine are relevant, consideration should also be given to the possibility of recurrence of PE with continued clozapine treatment (Selten and Buller, 2003) in the clinical decision-making process.