The effects of the second generation antipsychotics and a typical neuroleptic on collagen-induced platelet aggregation in vitro

Abstract

Objective. Antipsychotics are widely used in psychiatry, and consequently a lot of their side effects have been reported. One of them is cardiovascular disease leading to increased risk of stroke, thrombosis, pulmonary, embolism, in which hyperactivation of blood platelets is involved. The purpose of the present study was to examine the effects of the second generation antipsychotics (SGAs) such as clozapine, risperidone, and olanzapine, and a typical neuroleptic – haloperidol – on the one step of platelet activation–platelet aggregation induced by collagen in vitro. Blood was collected into buffered sodium citrate (3.8%) and centrifuged to get platelet-rich plasma (PRP). In PRP (2×108 platelets/ml) obtained from healthy volunteers that was incubated with antipsychotics (clozapine, risperidone, olanzapine, haloperidol; 30 min) aggregation of blood platelets was measured using a Chrono-Log Lumi-aggregometer. Aggregation of platelets was measured after stimulation of platelets with 1 µl of collagen (2 µg/ml). Results. Clozapine, like haloperidol reduced platelet aggregation induced by collagen (inhibition of platelet aggregation reached about 20%) (P=1×10−5 and P=0.003, respectively). Risperidone had also a weak antiaggregatory effect (P=0.05). Among tested antipsychotics only olanzapine had no effect on collagen-stimulated platelet aggregation (P>0.05). Conclusion. The obtained results indicate that the difference in action of tested drugs on platelet aggregation may dependent on the various chemical structures of these drugs. Clozapine, risperidone and haloperidol are structurally diverse, and they all significantly reduce platelet aggregability induced by collagen. On the other hand, a close structural analog of clozapine – olanzapine – did not inhibit platelet aggregation. However, mechanism of antipsychotics action on blood platelets is not clear. Moreover, it seems that clozapine, risperidone and haloperidol treatment due to antiaggregatory action may have even some antithrombotic effects.