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Functional Testing for Tranexamic Acid Duration of Action Using Modified Viscoelastometry
Transfusion Medicine and Hemotherapy ( IF 1.9 ) Pub Date : 2020-11-09 , DOI: 10.1159/000511230
Tobias Kammerer 1, 2 , Philipp Groene 1 , Sophia R Sappel 1 , Sven Peterss 3 , Paula A Sa 4 , Thomas Saller 1 , Andreas Giebl 5 , Patrick Scheiermann 1 , Christian Hagl 3 , Simon Thomas Schäfer 1
Affiliation  

Introduction: Tranexamic acid (TXA) is the standard medication to prevent or treat hyperfibrinolysis. However, prolonged inhibition of lysis (so-called “fibrinolytic shutdown”) correlates with increased mortality. A new viscoelastometric test enables bedside quantification of the antifibrinolytic activity of TXA using tissue plasminogen activator (TPA). Materials and Methods: Twenty-five cardiac surgery patients were included in this prospective observational study. In vivo, the viscoelastometric TPA test was used to determine lysis time (LT) and maximum lysis (ML) over 96 h after TXA bolus. Additionally, plasma concentrations of TXA and plasminogen activator inhibitor 1 (PAI-1) were measured. Moreover, dose effect curves from the blood of healthy volunteers were performed in vitro. Data are presented as median (25–75th percentile). Results: In vivo TXA plasma concentration correlated with LT (r = 0.55; p #x3c; 0.0001) and ML (r = 0.62; p #x3c; 0.0001) at all time points. Lysis was inhibited up to 96 h (LTTPA-test: baseline: 398 s [229–421 s] vs. at 96 h: 886 s [626–2,175 s]; p = 0.0013). After 24 h, some patients (n = 8) had normalized lysis, but others (n = 17) had strong lysis inhibition (ML #x3c;30%; p #x3c; 0.001). The high- and low-lysis groups differed regarding kidney function (cystatin C: 1.64 [1.42–2.02] vs. 1.28 [1.01–1.52] mg/L; p = 0.002) in a post hoc analysis. Of note, TXA plasma concentration after 24 h was significantly higher in patients with impaired renal function (9.70 [2.89–13.45] vs.1.41 [1.30–2.34] µg/mL; p #x3c; 0.0001). In vitro, TXA concentrations of 10 µg/mL effectively inhibited fibrinolysis in all blood samples. Conclusions: Determination of antifibrinolytic activity using the TPA test is feasible, and individual fibrinolytic capacity, e.g., in critically ill patients, can potentially be measured. This is of interest since TXA-induced lysis inhibition varies depending on kidney function.
Transfus Med Hemother


中文翻译:

使用改良粘弹性法测定氨甲环酸作用时间的功能测试

简介:氨甲环酸(TXA)是预防或治疗过度纤维蛋白溶解的标准药物。然而,长时间的裂解抑制(所谓的“纤维蛋白溶解关闭”)与死亡率增加相关。一项新的弹性弹力测试可使用组织纤溶酶原激活剂(TPA)在床旁量化TXA的抗纤维蛋白溶解活性。材料和方法:该前瞻性观察研究纳入了25名心脏外科手术患者。在体内,使用粘弹性弹性体TPA测试确定在TXA推注后96小时内的裂解时间(LT)和最大裂解(ML)。此外,还测量了TXA和纤溶酶原激活物抑制剂1(PAI-1)的血浆浓度。此外,在体外绘制了健康志愿者血液的剂量效应曲线。数据以中位数(第25-75个百分点)表示。结果:在所有时间点,体内TXA血浆浓度均与LT(r = 0.55; p#x3c; 0.0001)和ML(r = 0.62; p#x3c; 0.0001)相关。裂解被抑制长达96小时(LTTPA测试:基准时间:398 s [229-421 s],而96小时时:886 s [626-2,175 s];p = 0.0013)。24小时后,一些患者(Ñ = 8)具有归一化的裂解,但其他(Ñ = 17)有很强的抑制的裂解(ML#X3C; 30%; p#X3C; 0.001)。在事后分析中,高溶解度和低溶解度组在肾功能方面有所不同(胱抑素C:1.64 [1.42-2.02] vs. 1.28 [1.01-1.52] mg / L;p = 0.002)。值得注意的是,肾功能受损的患者24小时后TXA血浆浓度显着更高(9.70 [2.89–13.45] µs / 1.41 [1.30–2.34] µg / mL;p#x3c; 0.0001)。在体外,TXA浓度为10 µg / mL可有效抑制所有血样中的​​纤维蛋白溶解。结论:使用TPA测试确定抗纤维蛋白溶解活性是可行的,并且可以潜在地测量个别纤维蛋白溶解能力,例如在危重患者中。这是令人感兴趣的,因为TXA诱导的裂解抑制作用取决于肾功能而变化。
Transfus Med Hemother
更新日期:2020-11-09
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