Application of a plasmin generation assay to define pharmacodynamic effects of tranexamic acid in women undergoing cesarean delivery.
Application of a plasmin generation assay to define pharmacodynamic effects of tranexamic acid in women undergoing cesarean delivery.
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DOI：
10.1111/jth.15114
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Wolberg AS
中科院分区：
文献类型：
--
作者：
Miszta A;Ahmadzia HK;Luban NLC;Li S;Guo D;Holle LA;Berger JS;James AH;Gobburu JVS;van den Anker J;de Laat B;Wolberg AS
氨甲环酸(TXA)用于减少出血。TXA抑制纤溶酶(原)与纤维蛋白的结合，减少纤溶。血栓素A的抗纤溶活性通常是通过凝块溶解试验来测量的；然而，由于缺乏测量血浆纤溶酶的工具，对纤溶酶生成(PG)的影响尚不清楚。建立一种测定人血浆中PG动力学的方法。测定TXA对PG的影响，并与旋转血栓弹力测定法(ROTEM)测定的纤溶功能进行比较。我们在体外研究了纤溶酶原、组织型纤溶酶原激活剂、纤维蛋白原和α-2-抗纤溶酶对PG的影响。我们还研究了剖宫产期间静脉注射血栓素A(5、10或15 mg/kg)对30例孕妇血浆前列腺素的影响。用校正荧光法测定PG。PG参数与血栓素A(TXA)质谱仪测定结果及全血生化指标进行比较。PG法对纤溶酶具有特异性，对组织型纤溶酶原激活剂、纤维蛋白原和α-2-抗纤溶酶敏感。体外血浆中加入TXA可剂量依赖性地延长血栓溶解时间，延缓和降低PG。静脉注射所有剂量的TXA后，PG法检测到峰值延迟时间(≤3小时)，并降低输注后血浆样本的速度、峰值和内源性纤溶酶电位(≤24小时)。PG到达峰值的时间、速度和峰值与TXA浓度显著相关，并且在30min或最大溶解时表现出比Rotem溶解指数更小的变异性。PG试验检测在体外和体内给予的TXA的药理相关浓度，并证明TXA介导的对剖宫产妇女PG的抑制。
Tranexamic acid (TXA) is used to reduce bleeding. TXA inhibits plasmin(ogen) binding to fibrin and reduces fibrinolysis. TXA antifibrinolytic activity is typically measured by clot lysis assays; however, effects on plasmin generation (PG) are unclear due to a lack of tools to measure PG in plasma. Develop an assay to measure PG kinetics in human plasma. Determine effects of TXA on PG and compare with fibrinolysis measured by rotational thromboelastometry (ROTEM). We characterized effects of plasminogen, tissue plasminogen activator, fibrinogen, and α2-antiplasmin on PG in vitro. We also studied effects of TXA on PG in plasma from 30 pregnant women administered intravenous TXA (5, 10, or 15 mg/kg) during cesarean delivery. PG was measured by calibrated fluorescence. PG parameters were compared with TXA measured by mass spectrometry and ROTEM of whole blood. The PG assay is specific for plasmin and sensitive to tissue plasminogen activator, fibrin(ogen), and α2-antiplasmin. Addition of TXA to plasma in vitro dose dependently prolonged the clot lysis time and delayed and reduced PG. For all doses of TXA administered intravenously, the PG assay detected delayed time-to-peak (≤3 hours) and reduced the velocity, peak, and endogenous plasmin potential (≤24 hours) in plasma samples obtained after infusion. The PG time-to-peak, velocity, and peak correlated significantly with TXA concentration and showed less variability than the ROTEM lysis index at 30 minutes or maximum lysis. The PG assay detects pharmacologically relevant concentrations of TXA administered in vitro and in vivo, and demonstrates TXA-mediated inhibition of PG in women undergoing cesarean delivery.
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DOI：
10.1016/s0301-2115(03)00287-2
发表时间：
2004-02-10
期刊：
EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY
影响因子：
--
作者：
Gai, MY;Wu, LF;Tatsumoto, K
通讯作者：
Tatsumoto, K
影响因子：
5.7
作者：
Gomez-Builes JC;Acuna SA;Nascimento B;Madotto F;Rizoli SB
通讯作者：
Rizoli SB
影响因子：
15.9
作者：
GOLDSMITH, GH;SAITO, H;RATNOFF, OD
通讯作者：
RATNOFF, OD
影响因子：
2.1
作者：
Dirkmann, D.;Hanke, A. A.;Peters, J.
通讯作者：
Peters, J.
DOI：
10.1136/bmj.e3054
发表时间：
2012-05-17
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Ker K;Edwards P;Perel P;Shakur H;Roberts I
通讯作者：
Roberts I