Tranexamic acid toxicity in human periarticular tissues

McLean, M. et al. (2019) Tranexamic acid toxicity in human periarticular tissues. Bone and Joint Research, 8(1), pp. 11-18. (doi: 10.1302/2046-3758.81.BJR-2018-0181.R1) (PMID:30800295) (PMCID:PMC6359888)

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Abstract

Objectives: Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. Methods: Tendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for ex vivo and in vitro studies using various concentrations of TXA. The in vitro effect of TXA on primary cultured tenocytes, fibroblast-like synoviocytes, and chondrocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays, fluorescent microscopy, and multi-protein apoptotic arrays for cell death. Results: There was a significant (p < 0.01) increase in cell death within all tissue explants treated with 100 mg/ml TXA. MTT assays revealed a significant (p < 0.05) decrease in cell viability in all tissues following treatment with 50 mg/ml or 100 mg/ml of TXA within four hours. There was a significant (p < 0.05) increase in cell apoptosis after one hour of exposure to TXA (100 mg/ml) in all tissues. Conclusion: The current study demonstrates that TXA caused significant periarticular tissue toxicity ex vivo and in vitro at commonly used clinical concentrations.

Item Type:Articles
Additional Information:This work was supported by the Royal College of Surgeons (Edinburgh) through a pump priming small research grant and Arthritis Research UK (21346).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Smith, Dr Innes and McCall, Kathryn and Akbar, Mr Moeed and Kitson, Miss Susan and McLean, Michael and Blyth, Mr Mark and Crowe, Ms Lindsay and Millar, Professor Neal
Authors: McLean, M., McCall, K., Smith, I., Blyth, M., Kitson, S.M., Crowe, L.A.N., Leach, W.J., Rooney, B.P., Spencer, S.J., Mullen, M., Campton, J.L., McInnes, I.B., Akbar, M., and Millar, N.L.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Bone and Joint Research
Publisher:British Editorial Society of Bone and Joint Surgery
ISSN:2046-3758
ISSN (Online):2046-3758
Published Online:11 January 2019
Copyright Holders:Copyright © 2019 Authors et al.
First Published:First published in Bone and Joint Research 8(1):11
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
725711HMGB1: a key damage mediator in tendinopathyNeal MillarArthritis Research UK (ARTRESUK)21346III -IMMUNOLOGY