Niemi T T, Taxell C, Rosenberg P H
Department of Anaesthesiology, Helsinki University Central Hospital, Finland.
Acta Anaesthesiol Scand. 1997 Nov;41(10):1353-8. doi: 10.1111/j.1399-6576.1997.tb04657.x.
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis which may result in impaired platelet function. Because NSAIDs have different abilities to inhibit cyclo-oxygenases we compared the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers.
Ten healthy male volunteers were given ketoprofen 1.4 mg x kg(-1), ketorolac 0.4 mg x kg(-1) and diclofenac 1.1 mg x kg(-1) in saline i.v. on three different occasions, at more than one-week intervals, in a randomized double-blind crossover study. Platelet function was evaluated before (sample 0), 2 (sample 2) and 24 h (sample 3) after the beginning of the infusion.
Two of the volunteers had no secondary platelet aggregation in their aggregation curves before the experiment (sample 0, studied three times) and their results were excluded from the final analysis. Diclofenac inhibited adrenaline (0.9 microg x m[-1]) induced platelet aggregation less (median maximal aggregation 22.5%) than ketoprofen (18.3%) and ketorolac (15.7%) (P<0.05) in sample 2. In the ketorolac group in sample 3 an impairment of adrenaline (0.9 microg x ml[-1]) induced platelet aggregation was still seen (26.7%) (P<0.05) but not in the other groups. Diclofenac did not affect adenosine diphosphate (ADP) induced platelet aggregation. However, ketorolac caused an impairment in ADP (3 microM and 6 microM) induced platelet aggregation and ketoprofen in ADP (6 microM) induced platelet aggregation in sample 2. Bleeding time was prolonged (P<0.05) after ketoprofen and ketorolac (sample 2) but not after diclofenac. Platelet retention on glass beads was unaffected by the tested drugs.
Ketoprofen, ketorolac and diclofenac caused a reversible platelet dysfunction. Diclofenac had the mildest effect, while platelet dysfunction was still seen 24 h after the beginning of ketorolac.
非甾体抗炎药（NSAIDs）抑制前列腺素合成，这可能导致血小板功能受损。由于NSAIDs抑制环氧化酶的能力不同，我们比较了静脉注射酮洛芬、酮咯酸和双氯芬酸对志愿者血小板功能的影响。
在一项随机双盲交叉研究中，10名健康男性志愿者在三个不同时间，间隔超过一周，静脉注射生理盐水溶解的酮洛芬1.4mg/kg、酮咯酸0.4mg/kg和双氯芬酸1.1mg/kg。在输注开始前（样本0）、2小时（样本2）和24小时（样本3）评估血小板功能。
两名志愿者在实验前（样本0，研究三次）的聚集曲线中无继发性血小板聚集，其结果被排除在最终分析之外。在样本2中，双氯芬酸抑制肾上腺素（0.9μg/ml）诱导的血小板聚集作用（最大聚集中位数为22.5%）小于酮洛芬（18.3%）和酮咯酸（15.7%）（P<0.05）。在样本3中，酮咯酸组仍可见肾上腺素（0.9μg/ml）诱导的血小板聚集受损（26.7%）（P<0.05），而其他组未见。双氯芬酸不影响二磷酸腺苷（ADP）诱导的血小板聚集。然而，在样本2中，酮咯酸导致ADP（3μM和6μM）诱导的血小板聚集受损，酮洛芬导致ADP（6μM）诱导的血小板聚集受损。酮洛芬和酮咯酸（样本2）后出血时间延长（P<0.05），而双氯芬酸后未延长。玻璃珠上的血小板滞留不受所测试药物的影响。
酮洛芬、酮咯酸和双氯芬酸引起可逆性血小板功能障碍。双氯芬酸的作用最轻微，而酮咯酸开始使用24小时后仍可见血小板功能障碍。
