Tranexamic Acid in the Procedural Setting
Tranexamic acid (TXA) is an antifibrinolytic agent, a medication that reduces bleeding by preventing the lysis of a blood clot.1 Originally developed for patients with hemophilia undergoing oral surgery, TXA is now also administered to reduce heavy menstrual bleeding, treat trauma patients at risk for hemorrhage, and to preoperatively minimize the need for blood transfusions during surgery.2 TXA is an analog of the amino acid lysine and it functions by blocking the conversion of plasminogen to the enzyme plasmin, which breaks down blood clots by attacking fibrin.2 TXA was first synthesized in 1962 and is currently on the World Health Organization’s Model List of Essential Medicines. 3,4
In the surgical setting, TXA is commonly used for major orthopedic surgery, which often involves significant blood loss and requires transfusions.5 Specifically, a little less than a third of patients undergoing total joint arthroplasty require postoperative blood transfusions for anemia.6 Studies7,8 have shown that intravenous TXA reduces blood loss and transfusion requirements for both total knee and hip arthroplasties. The safety and efficacy of topical and intra-articular TXA for total joint arthroplasty has also been established in the literature.9
In addition to orthopedic surgery, spine surgery can often entail a large volume of blood loss and is likewise often accompanied by the administration of TXA. Blood loss during posterior instrumented spinal fusion was found to be reduced by as much as 30% in patients given TXA before the operation.10 The efficacy of TXA for pediatric and adolescent patients has also been established in some situations: studies have shown that younger patients who receive intravenous TXA before scoliosis surgery demonstrate a dramatic decrease in blood loss.11 While some studies, such as one investigating the perioperative use of TXA for fusion of the thoracic and lumbar spine,12 have not found a significant difference in blood loss for patients given TXA, most clinical trials are in fact indicating that TXA can effectively control blood loss during spinal surgery.10
The use of TXA, while known to prevent the lysis of blood clots, may concurrently increase the risk of thromboembolism, the obstruction of a blood vessel by a blood clot dislodged from another site. The 2012 “MATTER” study, which investigated the use of TXA in combat injury, demonstrated higher rates of thromboembolism in patients receiving TXA.13 Similarly, a 2018 study concluded that TXA administration was an independent risk factor for thromboembolism.14
However, these studies may be misleading. Myers et al.15 note that in those studies, TXA is only given to the sickest patients, who may already be at a much higher risk for thromboembolism, thus confounding any potential results. Many of these retrospective studies do not routinely screen for thromboembolism, which may present another methodological problem. Many more studies, in fact, have found that TXA does not present a significant risk for thromboembolism. For example, a recent systematic review and meta-analysis of hundreds of studies did not reveal an increased risk of thromboembolic events in any patient group.16 While patients should certainly be made aware of the potential for developing thromboembolic events upon receiving TXA, the risk appears to be quite low, and most researchers believe it should not prevent physicians from administering this vital drug.
References
1. McEvoy, M. “Tranexamic Acid (TXA): Drug Whys.” EMS1, Lexipol, 29 June 2015, www.ems1.com/ems-products/ambulance-disposable-supplies/articles/tranexamic-acid-txa-drug-whys-JHdJgbiQRX2zqonO/.
2. Thomas, J. “The Benefits of TXA.” EMS World, 5 Feb. 2015, www.emsworld.com/article/12042127/tranexamic-acid-for-prehospital-hemorrhage.
3. “TXA: History.” TXA Central, London School of Hygiene & Tropical Medicine, txacentral.lshtm.ac.uk/?page_id=98.
4. Gill, R., et al. “WHO Essential Medicines for Reproductive Health.” BMJ Global Health, vol. 4, no. 6, 2019, doi:10.1136/bmjgh-2019-002150.
5. Davey, J. Roderick, et al. “Tranexamic Acid for the Prevention and Management of Orthopedic Surgical Hemorrhage: Current Evidence.” Journal of Blood Medicine, 2015, p. 239., doi:10.2147/jbm.s61915.
6. Blumberg, N., et al. “A Cost Analysis of Autologous and Allogeneic Transfusions in Hip-Replacement Surgery.” The American Journal of Surgery, vol. 171, no. 3, 1996, pp. 324–330., doi:10.1016/s0002-9610(97)89635-3.
7. Ekbäck, G., et al. “Tranexamic Acid Reduces Blood Loss in Total Hip Replacement Surgery.” Anesthesia & Analgesia, vol. 91, no. 5, 2000, pp. 1124–1130., doi:10.1097/00000539-200011000-00014.
8. Good, L., et al. “Tranexamic Acid Decreases External Blood Loss but Not Hidden Blood Loss in Total Knee Replacement.” British Journal of Anaesthesia, vol. 90, no. 5, 2003, pp. 596–599., doi:10.1093/bja/aeg111.
9. Wong, J., et al. “Topical Application of Tranexamic Acid Reduces Postoperative Blood Loss in Total Knee Arthroplasty.” The Journal of Bone and Joint Surgery-American Volume, vol. 92, no. 15, 2010, pp. 2503–2513., doi:10.2106/jbjs.i.01518.
10. Yoo, J. S., et al. “The Use of Tranexamic Acid in Spine Surgery.” Annals of Translational Medicine, vol. 7, no. S5, 2019, doi:10.21037/atm.2019.05.36.
11. Verma, K., et al. “The Relative Efficacy of Antifibrinolytics in Adolescent Idiopathic Scoliosis.” Journal of Bone and Joint Surgery, vol. 96, no. 10, 2014, doi:10.2106/jbjs.l.00008.
12. Farrokhi, M. R., et al. “Efficacy of Prophylactic Low Dose of Tranexamic Acid in Spinal Fixation Surgery.” Journal of Neurosurgical Anesthesiology, vol. 23, no. 4, 2011, pp. 290–296., doi:10.1097/ana.0b013e31822914a1.
13. Morrison, J. J. “Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study.” Archives of Surgery, vol. 147, no. 2, 2012, p. 113., doi:10.1001/archsurg.2011.287.
14. Johnston, L. R., et al. “Evaluation of Military Use of Tranexamic Acid and Associated Thromboembolic Events.” JAMA Surgery, vol. 153, no. 2, 2018, p. 169., doi:10.1001/jamasurg.2017.3821.
15. Myers, S. P., et al. “Venous Thromboembolism after Tranexamic Acid Administration: Legitimate Risk or Statistical Confounder?” ANZ Journal of Surgery, vol. 90, no. 4, 2020, pp. 425–426., doi:10.1111/ans.15670.
16. Taeuber, I., et al. “Association of Intravenous Tranexamic Acid With Thromboembolic Events and Mortality.” JAMA Surgery, vol. 156, no. 6, 2021, doi:10.1001/jamasurg.2021.0884.