氨甲环酸剂量对剖宫产产后出血抗纤溶反应关系的研究:TRACES，一项双盲、安慰剂对照、多中心、剂量范围生物标志物研究
贵州医科大学 麻醉与心脏电生理课题组
翻译：王子君 编辑：柏雪 审校：曹莹
背景:氨甲环酸抑制产后出血高纤溶的最佳剂量尚不清楚。氨甲环酸减少出血性剖宫产出血量(TRACES)是一项双盲、安慰剂对照、随机、多中心剂量范围研究，旨在确定静脉注射氨甲环酸与安慰剂两种方案的剂量效应关系。
方法:将剖宫产期间出现产后出血的女性患者随机分为安慰剂组(n=60)、氨甲环酸0.5 g组(n=57)或氨甲环酸1g组(n=58)。在五个时间点检测纤溶激活的生物标志物，对高纤溶的抑制定义为D-二聚体和纤溶酶-抗纤溶酶水平在基线上的增加以及纤溶酶峰值时间的减少。
结果:在安慰剂组中，120分钟时D-二聚体水平比基线平均增加93% [68-118]，30分钟时抗血纤维蛋白溶素水平比基线平均增加56% [25-87]，证明了高纤溶发生。1 g剂量的氨甲环酸与基线的较小增加相关(D-二聚体:38% [13-63] [P=0.003 vs安慰剂];血浆抗纤溶酶:-2% [-32 ~ 28] [P=0.0019 vs安慰剂])。0.5 g剂量的氨甲环酸效果较差，无显著性降低(d -二聚体:58% [32-84] [P=0.06 vs安慰剂]；血浆抗纤溶酶:13% [18-43] [P=0.051])。虽然两种剂量的氨甲环酸都降低了纤溶酶峰，但只有1 g剂量的氨甲环酸才显著降低了纤溶酶峰时间。
结论:静脉注射氨甲环酸1 g显著抑制纤溶活性，而0.5 g无明显抑制作用。这些数据的药代动力学药效学建模可以确定治疗产后出血的最佳药效学监测标准和最佳氨甲环酸给药方案。
原始文献来源：Anne-Sophie Ducloy-Bouthors , Sixtine Gilliot , Maeva Kyheng el.at. Tranexamic acid dose-response relationship for antifibrinolysis in postpartum haemorrhage during Caesarean delivery: TRACES, a double-blind, placebo-controlled, multicentre, dose-ranging biomarker study. Br J Anaesth. 2022 Dec;129(6):937-945. doi: 10.1016/j.bja.2022.08.033. Epub 2022 Oct 13.
Tranexamic acid doseeresponse relationship for antifibrinolysis in
postpartum haemorrhage during Caesarean delivery: TRACES, a
double-blind, placebo-controlled, multicentre, dose-ranging
biomarker study
Abstract
Background: The optimal dose of tranexamic acid to inhibit hyperfibrinolysis in postpartum haemorrhage is unclear. Tranexamic Acid to Reduce Blood Loss in Hemorrhagic Cesarean Delivery (TRACES) was a double-blind, placebocontrolled, randomised, multicentre dose-ranging study to determine the doseeeffect relationship for two regimens of intravenous tranexamic acid vs placebo.
Methods: Women experiencing postpartum haemorrhage during Caesarean delivery were randomised to receive placebo(n¼60), tranexamic acid 0.5 g (n=57), or tranexamic acid 1 g i.v. (n=58). Biomarkers of fibrinolytic activation were assayed at five time points, with inhibition of hyperfibrinolysis defined as reductions in the increase over baseline in D-dimer and plasmine-antiplasmin levels and in the plasmin peak time.
Results: In the placebo group, hyperfibrinolysis was evidenced by a mean increase over baseline [95% confidence interval] of 93% [68-118] for D-dimer level at 120 min and 56% [25-87] for the plasmine-antiplasmin level at 30 min. A dose of tranexamic acid 1 g was associated with smaller increases over baseline (D-dimers: 38% [13-63] [P=0.003 vs placebo];plasmine-antiplasmin: -2% [-32 to 28] [P=0.009 vs placebo]). A dose of tranexamic acid 0.5 g was less potent, with nonsignificant reductions (D-dimers: 58% [32-84] [P=0.06 vs placebo]; plasmine-antiplasmin: 13% [18-43] [P=0.051]). Although both tranexamic acid doses reduced the plasmin peak, reduction in plasmin peak time was significant only for the 1 g dose of tranexamic acid.
Conclusions: Fibrinolytic activation was significantly inhibited by a dose of intravenous tranexamic acid 1 g but not 0.5 g. Pharmacokineticepharmacodynamic modelling of these data might identify the best pharmacodynamic monitoring criteria and the optimal tranexamic acid dosing regimen for treatment of postpartum haemorrhage.
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