Department of Affective and Psychotic Disorders, Medical University of Lodz, Lodz, Poland.
World J Biol Psychiatry. 2010 Mar;11(2 Pt 2):268-75. doi: 10.3109/15622970802505792.
Blood platelets play an important role in haemostasis and their hyperaggregability may lead to thrombosis and cardiovascular diseases. Increased incidence of mortality, caused by cardiovascular disease, and the increased risk of thrombotic complication in schizophrenic patients treated with antipsychotics have been reported. The effects of antipsychotic drugs on blood platelet function are not fully explained, therefore the purpose of the present study was to examine and compare the effects of the second-generation antipsychotic drugs used in schizophrenia (clozapine, risperidone and olanzapine), with the effects of the first generation antipsychotic, haloperidol, on the platelet aggregation induced by ADP in vitro.
Blood obtained from healthy volunteers (n=25) collected into sodium citrate was centrifuged (250xg, 10 min) at room temperature to obtain platelet-rich plasma. Aggregation of blood platelets (10 microM ADP) was recorded (Chrono-log aggregometer) in platelet-rich plasma preincubated with antipsychotic drugs (final concentration: clozapine 420 ng/ml, risperidone 65 ng/ml, olanzapine 40 ng/ml, haloperidol 20 ng/ml) for 30 min.
Our results showed that all tested drugs inhibit platelet aggregation induced by ADP in vitro. Among studied antipsychotic drugs clozapine and olanzapine significantly reduced platelet aggregability in vitro. In comparison with control platelets (without the drug), clozapine inhibited ADP-induced platelet aggregation by 21% (P=3.7x10(-6)) and olanzapine by 18% (P=2.8x10(-4)), respectively.
The obtained results indicate that antipsychotic drugs, especially clozapine and olanzapine, contrary to haloperidol, reduced response of blood platelets to ADP measured as platelet aggregation. This suggests that therapy with such antipsychotics, particularly with second-generation antipsychotics, may partly reduce prothrombotic events associated with the increased platelet activation observed in schizophrenic patients. The mechanism of antiaggregatory influence of antipsychotics requires further studies.
血小板在止血中起着重要作用，其过度聚集可能导致血栓形成和心血管疾病。据报道，心血管疾病导致的死亡率增加，以及接受抗精神病药物治疗的精神分裂症患者发生血栓并发症的风险增加。抗精神病药物对血小板功能的影响尚未得到充分解释，因此本研究旨在检查和比较用于治疗精神分裂症的第二代抗精神病药物（氯氮平、利培酮和奥氮平）与第一代抗精神病药物氟哌啶醇对体外 ADP 诱导的血小板聚集的影响。
从健康志愿者（n=25）采集的枸橼酸钠血液在室温下以 250xg 离心（10 分钟）以获得富含血小板的血浆。在富含血小板的血浆中预孵育抗精神病药物（最终浓度：氯氮平 420ng/ml、利培酮 65ng/ml、奥氮平 40ng/ml、氟哌啶醇 20ng/ml）30 分钟后，记录富含血小板的血浆中血小板（10μM ADP）的聚集情况（Chrono-log 聚集仪）。
我们的结果表明，所有测试的药物均抑制体外 ADP 诱导的血小板聚集。在所研究的抗精神病药物中，氯氮平和奥氮平显著降低了体外血小板的聚集能力。与无药物的对照血小板相比，氯氮平抑制 ADP 诱导的血小板聚集 21%（P=3.7x10(-6)），奥氮平抑制 18%（P=2.8x10(-4)）。
研究结果表明，抗精神病药物，特别是氯氮平和奥氮平，与氟哌啶醇相反，降低了血液血小板对 ADP 诱导的血小板聚集的反应。这表明，使用此类抗精神病药物治疗，特别是使用第二代抗精神病药物，可能部分减少与精神分裂症患者中观察到的血小板过度激活相关的促血栓形成事件。抗精神病药物的抗聚集作用机制需要进一步研究。
