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Kammerer, Tobias; Groene, Philipp; Sappel, Sophia R.; Peterss, Sven; Sa, Paula A.; Saller, Thomas; Giebl, Andreas; Scheiermann, Patrick; Hagl, Christian; Schaefer, Simon Thomas (2020): Functional Testing for Tranexamic Acid Duration of Action Using Modified Viscoelastometry. In: Transfusion Medicine and Hemotherapy, Vol. 48, No. 2: pp. 109-117
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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 < 0.0001) and ML (r = 0.62;p < 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 p < 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] mu g/mL;p < 0.0001). In vitro, TXA concentrations of 10 mu g/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.