Toxicity of tranexamic acid (TXA) to intra-articular tissue in orthopaedic surgery: a scoping review
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Toxicity of tranexamic acid (TXA) to intra‑articular tissue in orthopaedic surgery: a scoping review Scott M. Bolam1,2 · Arama O’Regan‑Brown1 · A. Paul Monk2,3 · David S. Musson1 · Jillian Cornish1 · Jacob T. Munro1,2 Received: 6 May 2020 / Accepted: 6 August 2020 © European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA) 2020
Abstract Purpose Intra-articular administration of tranexamic acid (TXA) in orthopaedic arthroplasty and arthroscopic procedures has become increasingly common over the past decade. However, several recent reports have shown that TXA has the potential to be cytotoxic to cartilage, tendon and synovium. Our aim was to review the literature for evidence of toxic effects from TXA exposure to intra-articular tissue. Methods A scoping review methodology was used to search for studies assessing the toxic effects of TXA exposure to intra-articular tissues. MEDLINE, EMBASE, SCOPUS and The Cochrane Library were searched. Relevant information was extracted and synthesis of the retrieved data followed a basic content analytical approach. Results A total of 15 laboratory studies were retrieved. No clinical studies reporting a toxic effect of TXA on intra-articular tissue were identified in our search. Studies were analysed according to species of origin, tissue of origin and study setting (in vitro, ex vivo, or in vivo). There was increasing cytotoxicity to chondrocytes, tenocytes, synoviocytes and periosteumderived cells with TXA concentrations beyond 20 mg/ml. Monolayer cell cultures appear more susceptible to TXA exposure, than three-dimensional and explant culture models. In vivo studies have not demonstrated a major toxic effect. Conclusions Current evidence suggests a dose-dependent toxic effect on cartilage, tendon, and synovial tissue. Concentrations of 20 mg/ml or less are expected to be safe. There is a significant body of evidence to suggest the need for caution with intraarticular administration of TXA. There is a need for further human clinical trials in order to clarify the long-term safety of TXA topical application. Abbreviations TXA Tranexamic acid IV Intravenous PRISMA-ScR Preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews ECM Extracellular matrix Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00167-020-06219-7) contains supplementary material, which is available to authorized users. * Scott M. Bolam [email protected] 1
Faculty of Medical and Health Sciences, University of Auckland, Building 502 201, 85 Park Road, Grafton 1023, New Zealand
2
Department of Orthopaedic Surgery, Auckland City Hospital, 2 Park Road, Grafton, New Zealand
3
Auckland Bioengineering Institute, University of Auckland, 70 Symonds St, Grafton 1010, New Zealand
2D Two-dimensional 3D Three-dimensional LDH Lactate dehydrogenase
Introduction Intra-articular tranexamic acid (TXA; Trans-4-aminomethylcyclohexane-1-carboxylic acid) administration is common in total hip
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