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体外研究 5-羟色胺和去甲肾上腺素再摄取抑制剂对人血小板黏附和凝血的影响。

In vitro effects of serotonin and noradrenaline reuptake inhibitors on human platelet adhesion and coagulation.

机构信息

Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.

出版信息

Pharmacol Rep. 2012;64(4):979-83. doi: 10.1016/s1734-1140(12)70894-0.

Abstract

BACKGROUND

Although several studies show that there is an increased risk of bleeding events during antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs), few studies show direct effects in vitro of SSRIs on hemostasis.

METHODS

This study was undertaken to investigate the effects on platelet adhesion and plasma coagulation (APTT and PT) of two common SSRIs, citalopram and sertraline, the selective noradrenaline reuptake inhibitor reboxetine, and the serotonin and noradrenaline reuptake inhibitor venlafaxine.

RESULTS

None of the compounds affected plasma coagulation significantly but all compounds except for venlafaxine inhibited platelet adhesion by approximately 50% or more at the highest concentration (100 μg/l, p < 0.01). The potency of respective compound to inhibit platelet adhesion to both collagen and fibrinogen surfaces was in the following order; citalopram > sertraline > reboxetine. In contrast, venlafaxine caused a weak but statistically significant increased platelet adhesion to fibrinogen.

CONCLUSION

This study showed that sertraline, citalopram and reboxetine direct and acutely decrease platelet adhesion to both collagen and fibrinogen in vitro. These results also indicate that increased risk for bleeding complications in antidepressant users may not only be explained by depletion of serotonin in platelets.

摘要

背景

尽管有几项研究表明,选择性 5-羟色胺再摄取抑制剂(SSRIs)在抗抑郁治疗中会增加出血事件的风险,但很少有研究显示 SSRIs 对止血的直接体外影响。

方法

本研究旨在调查两种常见的 SSRIs(西酞普兰和舍曲林)、选择性去甲肾上腺素再摄取抑制剂瑞波西汀以及 5-羟色胺和去甲肾上腺素再摄取抑制剂文拉法辛对血小板黏附及血浆凝血(APTT 和 PT)的影响。

结果

没有一种化合物对血浆凝血有显著影响,但除文拉法辛外,所有化合物在最高浓度(100μg/l,p<0.01)下均能抑制血小板黏附约 50%或更多。各化合物抑制血小板黏附至胶原蛋白和纤维蛋白原表面的效力依次为:西酞普兰>舍曲林>瑞波西汀。相比之下,文拉法辛导致纤维蛋白原上的血小板黏附略有但具有统计学意义的增加。

结论

本研究表明,舍曲林、西酞普兰和瑞波西汀直接且急性地减少血小板黏附至胶原蛋白和纤维蛋白原。这些结果还表明,抗抑郁药使用者出血并发症风险增加可能不仅归因于血小板中 5-羟色胺的耗竭。

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