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What concentration of tranexamic acid is needed to inhibit fibrinolysis? A systematic review of pharmacodynamics studies

Picetti, R; Shakur-Still, H; Medcalf, RL; Standing, JF; Roberts, I; (2019) What concentration of tranexamic acid is needed to inhibit fibrinolysis? A systematic review of pharmacodynamics studies. Blood Coagulation and Fibrinolysis , 30 (1) pp. 1-10. 10.1097/MBC.0000000000000789. Green open access

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Abstract

Intravenous tranexamic acid (TXA) reduces death because of bleeding in patients with trauma and postpartum haemorrhage. However, in some settings intravenous injection is not feasible. To find different routes of administration, we first need to determine the minimal concentration of TXA in the blood that is required to inhibit fibrinolysis. We conducted a systematic review of in-vitro and in-vivo pharmacodynamics studies. We searched MEDLINE, EMBASE, OviSP, and ISI Web of Science from database inception to November 2017 for all in-vitro (including simulated clotting models) or in-vivo studies reporting the relationship between the TXA concentration in blood or plasma and any reliable measure of fibrinolysis. We found 21 studies of which 20 were in vitro and one was in vivo. Most in-vitro studies stimulated fibrinolysis with tissue plasminogen activator and measured fibrinolysis using viscoelastic, optical density, or immunological assays. TXA concentrations between 10 and 15 mg/l resulted in substantial inhibition of fibrinolysis, although concentrations between 5 and 10 mg/l were partly inhibitory. TXA concentrations of 10–15 mg/l may be suitable targets for pharmacokinetic studies, although TXA concentrations above 5 mg/l may also be effective.

Type: Article
Title: What concentration of tranexamic acid is needed to inhibit fibrinolysis? A systematic review of pharmacodynamics studies
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/MBC.0000000000000789
Publisher version: https://doi.org/10.1097/MBC.0000000000000789
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0
Keywords: fibrinolysis, pharmacodynamics, systematic review, tissue plasminogen activator, tranexamic acid
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10069585
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