| Background and purposeAntipsychotics have been widely used in clinical practice since 1950s.From the first generation（typical）antipsychotics such as chlorpromazine and haloperidol to the second generation（atypical）antipsychotics,such as clozapine,olanzapine and risperidone,the side effects of antipsychotics have attracted much attention,including venous embolism caused by antipsychotics.Although studies have shown a significant correlation between antipsychotics and venous embolism,the results are inconsistent.Platelet hyperactivation and aggregation is an important initiating factor of thrombosis and thrombotic diseases.The physiological agonists of platelet aggregation include ADP,collagen and 5-HT.Therefore,by observing the effect of antipsychotics in vivo and in vitro on platelet aggregation and activation function,this study provides direction for further exploring the relationship between antipsychotics and venous thrombosis,and helps clinical rational drug use.Materials and methodsAccording to the concentration range of human blood,five antipsychotics,clozapine(4μg·ml-1,8μg·ml-1,10μg·ml-1,final concentration:276 ng·ml-1,552 ng·ml-1,690ng·ml-1),olanzapine(0.3μg·ml-1,0.6μg·ml-1,1.2μg·ml-1,final concentration:21 ng·ml-1,42ng·ml-1,83 ng·ml-1),risperidone(0.3μg·ml-1,0.6μg·ml-1,1.2μg·ml-1,final concentration:21ng·ml-1,42 ng·ml-1,83 ng·ml-1),quetiapine(2μg·ml-1,4μg·ml-1,8μg·ml-1,final concentration:138 ng·ml-1,276 ng·ml-1,552 ng·ml-1),and aripiprazole(2μg·ml-1,4μg·ml-1,8μg·ml-1,final concentration:138 ng·ml-1,276 ng·ml-1,552 ng·ml-1)were added to preincubate platelets respectively,and were induced by ADP,collagen and 5-HT to observe the effect of antipsychotics on platelet aggregation.Platelet aggregation was induced by platelet activator ADP,collagen,5-HT and epinephrine to observe the effect of long-term use of antipsychotics.Results were analyzed statistically by SPSS software.Results1.Rabbit platelets aggregation were induced by ADP(8.54 mg·L-1)after incubated with different antipsychotics in vitro.Clozapine(8μg·ml-1,final concentration:552 ng·ml-1)inhibited ADP-induced platelet aggregation by 20.2%（P<0.05）,olanzapine(1.2μg·ml-1,final concentration:83 ng·ml-1)by 15.0%（P<0.05）,risperidone(0.3μg·ml-1,1.2μg·ml-1,final concentration:21 ng·ml-1,83 ng·ml-1)by 22.1%and 20.5%respectively（P<0.05）.There was no significant difference on platelet aggregation between clozapine(4μg·ml-1,10μg·ml-1,final concentration:276 ng·ml-1,690 ng·ml-1)and control group（P>0.05）.There was no significant difference on platelet aggregation between olanzapine(0.3μg·ml-1,0.6μg·ml-1,final concentration:21 ng·ml-1,42 ng·ml-1)and control group（P>0.05）.There was no significant difference on platelet aggregation between risperidone(0.6μg·ml-1,final concentration:42ng·ml-1)and control group（P>0.05）.There was no significant difference on platelet aggregation between quetiapine(2μg·ml-1,4μg·ml-1,8μg·ml-1,final concentration:138 ng·ml-1,276ng·ml-1,552 ng·ml-1)and control group（P>0.05）.There was no significant difference on platelet aggregation between aripiprazole(2μg·ml-1,4μg·ml-1,8μg·ml-1,final concentration:138ng·ml-1,276 ng·ml-1,552 ng·ml-1)and control group（P>0.05）.2.After in vitro incubation of the rabbit platelets,clozapine(8μg·ml-1,final concentration:552 ng·ml-1)inhibited 5-HT and adrenaline-induced platelet aggregation by 47.5%（P<0.05）,clozapine(10μg·ml-1,final concentration:690 ng·ml-1)by 51.2%（P<0.01）,olanzapine(0.3μg·ml-1,0.6μg·ml-1,1.2μg·ml-1,final concentration:21 ng·ml-1,42 ng·ml-1,83ng·ml-1)by 69.7%,73.4%,80.2%（P<0.01）,risperidone(0.6μg·ml-1,1.2μg·ml-1,final concentration:42 ng·ml-1,83 ng·ml-1)by 88.2%,91.7%（P<0.01）.There was no significant difference on platelet aggregation between quetiapine(2μg·ml-1,4μg·ml-1,8μg·ml-1,final concentration:138 ng·ml-1,276 ng·ml-1,552 ng·ml-1)and control group（P>0.05）.There was no significant difference on platelet aggregation between aripiprazole(2μg·ml-1,4μg·ml-1,8μg·ml-1,final concentration:138 ng·ml-1,276 ng·ml-1,552 ng·ml-1)and control group（P>0.05）.3.The effect of continuous intraperitoneal injection of clozapine on platelet aggregation induced by ADP(4.27 mg·L-1)in rats.The results of analysis of variance showed that there was no significant difference in the total mean of platelet aggregation rate induced by ADP among the four groups（P>0.05）.4.There was no significant difference in the counts of platelets,the expression of GPⅡb-Ⅲa and the release of P-selectin between the clozapine(4μg·ml-1,8μg·ml-1,10μg·ml-1,final concentration:276 ng·ml-1,552 ng·ml-1,690 ng·ml-1)and the control group（P>0.05）.There were no significant differences in the counts of platelets,the expression of GPⅡb-Ⅲa and the release of P-selectin between the olanzapine(0.3μg·ml-1,0.6μg·ml-1,1.2μg·ml-1,final concentration:21 ng·ml-1,42 ng·ml-1,83 ng·ml-1)and the control group（P>0.05）.There was no significant difference in the counts of platelets,the expression of GPⅡb-Ⅲa and the release of P-selectin between the risperidone(0.3μg·ml-1,0.6μg·ml-1,1.2μg·ml-1,final concentration:21 ng·ml-1,42 ng·ml-1,83 ng·ml-1)and the control group（P>0.05）.Conclusion1.Clozapine,olanzapine and risperidone inhibited ADP induced platelet aggregation in rabbits,but quetiapine and aripiprazole did not.2.Clozapine,olanzapine and risperidone inhibited platelet aggregation induced by 5-HT and epinephrine in rabbits,but quetiapine and aripiprazole did not.3.Long term administration of clozapine had no effect on ADP induced platelet aggregation in rats.4.Clozapine,olanzapine and risperidone had no effect on the counts of platelets,the expression of GPⅡb-Ⅲa and the release of P-selectin on plateles. |
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