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眼局部给予非甾体类抗炎药后对血小板功能的抑制。

Inhibition of platelet function after ocular administration of non-steroidal anti-inflammatory drugs.

机构信息

Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Italy.

Department of Surgical and Biomedical Science, Section of Ophthalmology, University of Perugia, Perugia, Italy.

出版信息

Thromb Res. 2019 Mar;175:1-5. doi: 10.1016/j.thromres.2019.01.005. Epub 2019 Jan 11.

Abstract

INTRODUCTION

The use of topical NSAIDs is frequent in ophthalmology to reduce the local inflammatory reaction resulting from surgical procedures. Ocular use of some drugs was previously found to lead to significant systemic absorption with possible systemic effects. NSAIDs may enhance the hemorrhagic risk of anticoagulant and antiplatelet drugs. Aim of our study was to evaluate the systemic effects of two NSAIDs given by eyedrops on platelet COX-1 and on ex vivo and in vivo platelet activation.

MATERIALS AND METHODS

20 patients planned to undergo cataract surgery were randomized to the use of an ophthalmic solution containing Diclofenac or Indomethacin. Blood was taken at enrollment (baseline) and after 3 days of therapy (1 drop, 4 times a day). Arachidonic Acid (AA)-induced light transmission aggregometry (LTA), PFA-100® C-EPI, circulating platelet P-Selectin expression by flow cytometry and serum and AA-induced TxB production were evaluated before and after eyedrop therapy.

RESULTS

AA (0.1-0.2 mM)-induced LTA was significantly reduced after ocular indomethacin but not after diclofenac. PFA-100® C-EPI closure time was also significantly prolonged in the indomethacin group but not in the diclofenac group. Circulating platelet P-selectin expression was significantly reduced after treatment with indomethacin compared with diclofenac. Finally, treatment with eyedrop indomethacin, but not with diclofenac, strikingly suppressed AA-induced TxB generation, while treatment with diclofenac did not modify it.

CONCLUSIONS

Our data show that indomethacin administered by ophthalmic eye drops has a relevant systemic antiplatelet effect. This should be taken into account in patients under concurrent therapy with antiplatelet or anticoagulant agents.

摘要

简介

在眼科领域,局部使用非甾体抗炎药(NSAIDs)常用于减轻手术引起的局部炎症反应。先前发现一些眼部用药会导致明显的全身吸收,并可能产生全身作用。NSAIDs 可能会增加抗凝和抗血小板药物的出血风险。本研究旨在评估两种眼部用 NSAIDs 对血小板 COX-1 以及体外和体内血小板激活的全身作用。

材料和方法

20 例计划行白内障手术的患者被随机分为使用含双氯芬酸或吲哚美辛的眼用溶液组。分别在入组时(基线)和治疗 3 天后(每天滴 1 滴,4 次)采血。采用花生四烯酸(AA)诱导的光透射聚集(LTA)、PFA-100® C-EPI、流式细胞术检测循环血小板 P-选择素表达以及血清和 AA 诱导的 TxB 产生,在滴眼治疗前后进行评估。

结果

AA(0.1-0.2mM)诱导的 LTA 在眼部应用吲哚美辛后显著降低,但在双氯芬酸组无此作用。吲哚美辛组 PFA-100® C-EPI 闭合时间也显著延长,但双氯芬酸组无此作用。与双氯芬酸相比,吲哚美辛治疗后循环血小板 P-选择素表达显著降低。最后,滴眼用吲哚美辛治疗,而非双氯芬酸治疗,明显抑制 AA 诱导的 TxB 生成,而双氯芬酸治疗则不改变其作用。

结论

我们的数据表明,眼部应用吲哚美辛具有显著的全身抗血小板作用。在同时接受抗血小板或抗凝药物治疗的患者中应考虑这一点。

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