Major liver resection, systemic fibrinolytic activity, and the impact of tranexamic acid

Abstract

Background: Hyperfibrinolysis may occur due to systemic inflammation or hepatic injury that occurs during liver resection. Tranexamic acid (TXA) is an antifibrinolytic agent that decreases bleeding in various settings, but has not been well studied in patients undergoing liver resection.

Methods: In this prospective, phase II trial, 18 patients undergoing major liver resection were sequentially assigned to one of three cohorts: (i) Control (no TXA); (ii) TXA Dose I - 1 g bolus followed by 1 g infusion over 8 h; (iii) TXA Dose II - 1 g bolus followed by 10 mg/kg/hr until the end of surgery. Serial blood samples were collected for thromboelastography (TEG), coagulation components and TXA concentration.

Results: No abnormalities in hemostatic function were identified on TEG. PAP complex levels increased to peak at 1106 μg/L (normal 0-512 μg/L) following parenchymal transection, then decreased to baseline by the morning following surgery. TXA reached stable, therapeutic concentrations early in both dosing regimens. There were no differences between patients based on TXA.

Conclusions: There is no thromboelastographic evidence of hyperfibrinolysis in patients undergoing major liver resection. TXA does not influence the change in systemic fibrinolysis; it may reduce bleeding through a different mechanism of action. Registered with ClinicalTrials.gov: NCT01651182.

Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Figures

Figure 1

Trend in INR values at different time points (error bars represent standard error). Dashed line represents upper limit of normal range (1.10)

Figure 2

Trend in fibrinogen values at different time points (error bars represent standard error). Dashed line represents lower limit of normal range (2 g/L)

Figure 3

Trend in plasmin-antiplasmin (PAP) complex values at different time points (error bars represent standard error). Dashed line represents upper limit of normal range (512 μg/L)

Figure 4

Plasma concentration of TXA at different time points relative to bolus and infusion of TXA in patients (error bars represent standard error). Dashed line represents in-vitro therapeutic level of TXA (10 μg/mL)