TRANEXAMIC ACID IN PEDIATRIC CARDIAC SURGERY: A COMPREHENSIVE REVIEW OF EFFICACY, SAFETY, AND CURRENT CONTROVERSIES
Abstract
Pediatric patients undergoing cardiac surgery, particularly with cardiopulmonary bypass (CPB), are at high risk for significant bleeding and allogeneic blood transfusions due to their unique hemostatic profile. Tranexamic acid (TXA) is the primary antifibrinolytic agent used to mitigate this risk, but its efficacy, safety, and optimal administration in this population remain topics of debate. This article provides a comprehensive review and to synthesize the available evidence and identify critical knowledge gaps. Our analysis confirms that TXA significantly reduces postoperative blood loss and the need for allogeneic red blood cell and fresh frozen plasma transfusions. This effect was particularly notable in high-risk subgroups such as infants and cyanotic patients. Substantial heterogeneity was found across studies, primarily related to varying TXA dosing regimens and differing transfusion protocols, which limited the ability to define a single optimal dose. TXA is an effective agent for reducing bleeding and transfusion needs in pediatric cardiac surgery, but its use is associated with a potential, dose-dependent risk of seizures. The wide variability in dosing regimens and the lack of robust data on long-term neurological outcomes highlight a critical need for future large-scale, prospective trials. These studies should aim to standardize dosing protocols and definitively assess the true benefit-to-risk ratio of TXA in specific pediatric subgroups.
References
Aran, A. A., Karam, O., & Nellis, M. E. (2021). Bleeding in Critically Ill Children-Review of Literature, Knowledge Gaps, and Suggestions for Future Investigation. Front Pediatr, 9, 611680. https://doi.org/10.3389/fped.2021.611680
Bartucca, L. M., Shaykh, R., Stock, A., Dayton, J. D., Bacha, E., Haque, K. D., & Nellis, M. E. (2023). Epidemiology of severe bleeding in children following cardiac surgery involving cardiopulmonary bypass: use of Bleeding Assessment Scale for critically Ill Children (BASIC). Cardiology in the Young, 33(10), 1913-1919. https://doi.org/10.1017/S1047951122003493
Berri, J., Quintrec Donnette, M. L., Millet, I., Chenine, L., Serre, J. E., & Mazloum, M. (2025). Tranexamic acid-induced acute bilateral renal cortical necrosis in a young trauma patient: a case report and literature review. BMC Nephrology, 26(1), 95. https://doi.org/10.1186/s12882-025-03982-y
Bigdelian, H., Montazeri, M., Sedighi, M., Mansouri, M., & Amanollahi, A. (2023). Topical and Intravenous Tranexamic Acid in Acyanotic Children Undergoing Congenital Heart Surgery: A Randomized Clinical Trial. Journal of Surgical Research, 288, 64-70. https://doi.org/10.1016/j.jss.2023.02.029
Breuer, T., Martin, K., Wilhelm, M., Wiesner, G., Schreiber, C., Hess, J., Lange, R., & Tassani, P. (2009). The blood sparing effect and the safety of aprotinin compared to tranexamic acid in paediatric cardiac surgery. European Journal of Cardio-Thoracic Surgery, 35(1), 167-171; author reply 171. https://doi.org/10.1016/j.ejcts.2008.09.038
Bulutcu, F. S., Ozbek, U., Polat, B., Yalcin, Y., Karaci, A. R., & Bayindir, O. (2005). Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid, aprotinin or a combination? Paediatric Anaesthesia, 15(1), 41-46. https://doi.org/10.1111/j.1460-9592.2004.01366.x
Cardoso, B., Laranjo, S., Gomes, I., Freitas, I., Trigo, C., Fragata, I., Fragata, J., & Pinto, F. (2016). [Acute kidney injury after pediatric cardiac surgery: risk factors and outcomes. Proposal for a predictive model]. Revista Portuguesa de Cardiologia, 35(2), 99-104. https://doi.org/10.1016/j.repc.2015.06.006 (Insuficiencia renal aguda no contexto de cirurgia cardiaca pediatrica: fatores de risco e prognostico. Proposta de um modelo preditivo.)
Casares, J. A., Jaramillo, A. P., Nizamudeen, S., Valenzuela, A., Abdul Samad, S. K., & Rincon Gomez, A. S. (2024). Evaluating the Effectiveness of Tranexamic Acid vs. Placebo in Cardiac Surgery: A Systematic Review and Meta-Analysis. Cureus, 16(6), e63089. https://doi.org/10.7759/cureus.63089
Chauhan, S., Bisoi, A., Kumar, N., Mittal, D., Kale, S., Kiran, U., & Venugopal, P. (2004). Dose comparison of tranexamic acid in pediatric cardiac surgery. Asian Cardiovascular & Thoracic Annals, 12(2), 121-124. https://doi.org/10.1177/021849230401200208
Cholette, J. M., Faraoni, D., Goobie, S. M., Ferraris, V., & Hassan, N. (2018). Patient Blood Management in Pediatric Cardiac Surgery: A Review. Anesthesia and Analgesia, 127(4), 1002-1016. https://doi.org/10.1213/ANE.0000000000002504
Couture, P., Lebon, J. S., Laliberté, É., Desjardins, G., Chamberland, M., Ayoub, C., Rochon, A., Cogan, J., Denault, A., & Deschamps, A. (2017). Low-Dose Versus High-Dose Tranexamic Acid Reduces the Risk of Nonischemic Seizures After Cardiac Surgery With Cardiopulmonary Bypass. J Cardiothorac Vasc Anesth, 31(5), 1611-1617. https://doi.org/10.1053/j.jvca.2017.04.026
De Bonis, M., Cavaliere, F., Alessandrini, F., Lapenna, E., Santarelli, F., Moscato, U., Schiavello, R., & Possati, G. F. (2000). Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study. Journal of Thoracic and Cardiovascular Surgery, 119(3), 575-580. https://doi.org/10.1016/s0022-5223(00)70139-5
El Baser, I. I. A., ElBendary, H. M., & ElDerie, A. (2021). The synergistic effect of tranexamic acid and ethamsylate combination on blood loss in pediatric cardiac surgery. Annals of Cardiac Anaesthesia, 24(1), 17-23. https://doi.org/10.4103/aca.ACA_84_19
Faraoni, D., Rahe, C., & Cybulski, K. A. (2019). Use of antifibrinolytics in pediatric cardiac surgery: Where are we now? Paediatric Anaesthesia, 29(5), 435-440. https://doi.org/10.1111/pan.13533
Faraoni, D., Willems, A., Melot, C., De Hert, S., & Van der Linden, P. (2012). Efficacy of tranexamic acid in paediatric cardiac surgery: a systematic review and meta-analysis. European Journal of Cardio-Thoracic Surgery, 42(5), 781-786. https://doi.org/10.1093/ejcts/ezs127
Gertler, R., Wiesner, G., Tassani-Prell, P., Martin, K., & Gruber, M. (2014). Measurement of tranexamic acid serum concentrations in a 7-month-old infant with clinical seizures after open heart surgery. Pediatric Neurology, 51(2), e1-2. https://doi.org/10.1016/j.pediatrneurol.2014.04.003
Giordano, R., Palma, G., Poli, V., Palumbo, S., Russolillo, V., Cioffi, S., Mucerino, M., Mannacio, V. A., & Vosa, C. (2012). Tranexamic acid therapy in pediatric cardiac surgery: a single-center study. Annals of Thoracic Surgery, 94(4), 1302-1306. https://doi.org/10.1016/j.athoracsur.2012.04.078
Graham, E. M., Atz, A. M., Gillis, J., Desantis, S. M., Haney, A. L., Deardorff, R. L., Uber, W. E., Reeves, S. T., McGowan, F. X., Jr., Bradley, S. M., & Spinale, F. G. (2012). Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery. Journal of Thoracic and Cardiovascular Surgery, 143(5), 1069-1076. https://doi.org/10.1016/j.jtcvs.2011.08.051
Guzzetta, N. A., Allen, N. N., Wilson, E. C., Foster, G. S., Ehrlich, A. C., & Miller, B. E. (2015). Excessive postoperative bleeding and outcomes in neonates undergoing cardiopulmonary bypass. Anesthesia and Analgesia, 120(2), 405-410. https://doi.org/10.1213/ANE.0000000000000531
Hasegawa, T., Oshima, Y., Maruo, A., Matsuhisa, H., Tanaka, A., Noda, R., Yokoyama, S., & Iwasaki, K. (2014). Intraoperative tranexamic acid in pediatric bloodless cardiac surgery. Asian Cardiovascular & Thoracic Annals, 22(9), 1039-1045. https://doi.org/10.1177/0218492314527991
Hatami, F., Valizadeh, N., Salehi, F., & Hosseinzadeh Maleki, M. (2020). Topical versus low-dose systemic tranexamic acid in pediatric cardiac surgery: A randomized clinical study. Journal of Cardiac Surgery, 35(12), 3368-3373. https://doi.org/10.1111/jocs.15082
Ivasyk, I., Chatterjee, A., Jordan, C., Geiselmann, M. T., Chang, P. S., Kamel, H., & Khormaee, S. (2022). Evaluation of the safety of tranexamic acid use in pediatric patients undergoing spinal fusion surgery: a retrospective comparative cohort study. BMC Musculoskeletal Disorders, 23(1), 651. https://doi.org/10.1186/s12891-022-05604-2
Kratzer, S., Irl, H., Mattusch, C., Bürge, M., Kurz, J., Kochs, E., Eder, M., Rammes, G., & Haseneder, R. (2014). Tranexamic acid impairs γ-aminobutyric acid receptor type A-mediated synaptic transmission in the murine amygdala: a potential mechanism for drug-induced seizures? Anesthesiology, 120(3), 639-649. https://doi.org/10.1097/aln.0000000000000103
Lecker, I., Wang, D. S., Romaschin, A. D., Peterson, M., Mazer, C. D., & Orser, B. A. (2012). Tranexamic acid concentrations associated with human seizures inhibit glycine receptors. J Clin Invest, 122(12), 4654-4666. https://doi.org/10.1172/jci63375
Leyvi, G., Nelson, O., Yedlin, A., Pasamba, M., Belamarich, P. F., Nair, S., & Cohen, H. W. (2011). A comparison of the effect of aprotinin and epsilon-aminocaproic acid on renal function in children undergoing cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia, 25(3), 402-406. https://doi.org/10.1053/j.jvca.2011.01.015
Lin, C. Y., Shuhaiber, J. H., Loyola, H., Liu, H., Del Nido, P., DiNardo, J. A., & Pigula, F. A. (2015). The safety and efficacy of antifibrinolytic therapy in neonatal cardiac surgery. PloS One, 10(5), e0126514. https://doi.org/10.1371/journal.pone.0126514
Liu, C. W., Anih, J., Lebedeva, V., Gungor, A., Wang, C., Park, L., & Roshanov, P. S. (2024). Kidney disease in trials of perioperative tranexamic acid. Journal of Clinical Anesthesia, 94, 111417. https://doi.org/10.1016/j.jclinane.2024.111417
Madathil, T., Balachandran, R., Kottayil, B. P., Sundaram, K. R., & Nair, S. G. (2021). Comparison of efficacy of two different doses of tranexamic acid in prevention of post operative blood loss in patients with congenital cyanotic heart disease undergoing cardiac surgery. Annals of Cardiac Anaesthesia, 24(3), 339-344. https://doi.org/10.4103/aca.ACA_162_20
Maeda, T., Sasabuchi, Y., Matsui, H., Ohnishi, Y., Miyata, S., & Yasunaga, H. (2017). Safety of Tranexamic Acid in Pediatric Cardiac Surgery: A Nationwide Database Study. Journal of Cardiothoracic and Vascular Anesthesia, 31(2), 549-553. https://doi.org/10.1053/j.jvca.2016.10.001
Martin, K., Breuer, T., Gertler, R., Hapfelmeier, A., Schreiber, C., Lange, R., Hess, J., & Wiesner, G. (2011a). Tranexamic acid versus ɛ-aminocaproic acid: efficacy and safety in paediatric cardiac surgery. Eur J Cardiothorac Surg, 39(6), 892-897. https://doi.org/10.1016/j.ejcts.2010.09.041
Martin, K., Breuer, T., Gertler, R., Hapfelmeier, A., Schreiber, C., Lange, R., Hess, J., & Wiesner, G. (2011b). Tranexamic acid versus varepsilon-aminocaproic acid: efficacy and safety in paediatric cardiac surgery. European Journal of Cardio-Thoracic Surgery, 39(6), 892-897. https://doi.org/10.1016/j.ejcts.2010.09.041
Moynihan, K. M., Ryerson, L. M., Le, J., Nicol, K., Watt, K., Gadepalli, S. K., Alexander, P. M. A., Muszynski, J. A., Gehred, A., Lyman, E., Steiner, M. E., Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE, i. c. w. t. P. C. C. B. R. N., Pediatric Acute Lung, I., Sepsis Investigators, N., the Pediatric, E. s. o. P., & the Extracorporeal Life Support, O. (2024). Antifibrinolytic and Adjunct Hemostatic Agents: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference. Pediatric Critical Care Medicine, 25(7 Suppl 1), e44-e52. https://doi.org/10.1097/PCC.0000000000003491
Mueller, X. M., Tinguely, F., Tevaearai, H. T., Ravussin, P., Stumpe, F., & von Segesser, L. K. (2000). Impact of duration of chest tube drainage on pain after cardiac surgery. European Journal of Cardio-Thoracic Surgery, 18(5), 570-574. https://doi.org/10.1016/s1010-7940(00)00515-7
Murao, S., Nakata, H., Roberts, I., & Yamakawa, K. (2021). Effect of tranexamic acid on thrombotic events and seizures in bleeding patients: a systematic review and meta-analysis. Critical Care (London, England), 25(1), 380. https://doi.org/10.1186/s13054-021-03799-9
Murkin, J. M., Falter, F., Granton, J., Young, B., Burt, C., & Chu, M. (2010). High-dose tranexamic Acid is associated with nonischemic clinical seizures in cardiac surgical patients. Anesthesia and Analgesia, 110(2), 350-353. https://doi.org/10.1213/ANE.0b013e3181c92b23
Muthialu, N., Balakrishnan, S., Sundar, R., & Muralidharan, S. (2015). Efficacy of tranexamic acid as compared to aprotinin in open heart surgery in children. Annals of Cardiac Anaesthesia, 18(1), 23-26. https://doi.org/10.4103/0971-9784.148316
Nishida, T., Kinoshita, T., & Yamakawa, K. (2017). Tranexamic acid and trauma-induced coagulopathy. J Intensive Care, 5, 5. https://doi.org/10.1186/s40560-016-0201-0
Pasquali, S. K., Li, J. S., He, X., Jacobs, M. L., O'Brien, S. M., Hall, M., Jaquiss, R. D., Welke, K. F., Peterson, E. D., Shah, S. S., & Jacobs, J. P. (2012). Comparative analysis of antifibrinolytic medications in pediatric heart surgery. Journal of Thoracic and Cardiovascular Surgery, 143(3), 550-557. https://doi.org/10.1016/j.jtcvs.2011.06.048
Patel, J., Prajapati, M., Patel, H., Gandhi, H., Deodhar, S., & Pandya, H. (2017). Topical and low-dose intravenous tranexamic acid in cyanotic cardiac surgery. Asian Cardiovascular & Thoracic Annals, 25(2), 118-122. https://doi.org/10.1177/0218492316688416
Pouard, P. (2008). Blood Conservation in Pediatric Cardiac Surgery. Transfusion Alternatives in Transfusion Medicine, 7(1), 58-62. https://doi.org/10.1111/j.1778-428X.2005.tb00155.x
Radhakrishnan, V., & Mehra, N. (2020). Tranexamic acid-induced acute renal failure in a pediatric patient with acute myeloid leukemia: A cautionary note. Cancer Research, Statistics, and Treatment, 3(3). https://doi.org/10.4103/crst.Crst_158_20
Reid, R. W., Zimmerman, A. A., Laussen, P. C., Mayer, J. E., Gorlin, J. B., & Burrows, F. A. (1997). The efficacy of tranexamic acid versus placebo in decreasing blood loss in pediatric patients undergoing repeat cardiac surgery. Anesthesia and Analgesia, 84(5), 990-996. https://doi.org/10.1097/00000539-199705000-00008
Schertz, K., Karam, O., Demetres, M., Mayadunna, S., Faraoni, D., & Nellis, M. E. (2022). Prophylactic Use of Antifibrinolytics During Pediatric Cardiac Surgery With Cardiopulmonary Bypass on Postoperative Bleeding and Transfusion: A Systematic Review and Meta-Analysis. Pediatric Critical Care Medicine, 23(11), e517-e529. https://doi.org/10.1097/PCC.0000000000003049
Schindler, E., Photiadis, J., Sinzobahamvya, N., Dores, A., Asfour, B., & Hraska, V. (2011). Tranexamic acid: an alternative to aprotinin as antifibrinolytic therapy in pediatric congenital heart surgery. European Journal of Cardio-Thoracic Surgery, 39(4), 495-499. https://doi.org/10.1016/j.ejcts.2010.07.026
Siemens, K., Sangaran, D. P., Hunt, B. J., Murdoch, I. A., & Tibby, S. M. (2018). Strategies for Prevention and Management of Bleeding Following Pediatric Cardiac Surgery on Cardiopulmonary Bypass: A Scoping Review. Pediatric Critical Care Medicine, 19(1), 40-47. https://doi.org/10.1097/PCC.0000000000001387
Suieubekov, B., Sepbayeva, A., Yeshmanova, A., & Kusainov, A. (2023). Cardiac surgery-associated acute kidney injury in newborns: A meta-analysis. Electronic Journal of General Medicine, 20(2). https://doi.org/10.29333/ejgm/12805
Szarpak, L., Pruc, M., Dziedzic, K., & Perek, B. (2024). Systematic review and meta-analysis of tranexamic acid and epsilon aminocaproic acid in pediatric heart surgery. Kardiochir Torakochirurgia Pol, 21(2), 126-128. https://doi.org/10.5114/kitp.2024.141154
Taam, J., Yang, Q. J., Pang, K. S., Karanicolas, P., Choi, S., Wasowicz, M., & Jerath, A. (2020). Current Evidence and Future Directions of Tranexamic Acid Use, Efficacy, and Dosing for Major Surgical Procedures. Journal of Cardiothoracic and Vascular Anesthesia, 34(3), 782-790. https://doi.org/10.1053/j.jvca.2019.06.042
Tibi, P., McClure, R. S., Huang, J., Baker, R. A., Fitzgerald, D., Mazer, C. D., Stone, M., Chu, D., Stammers, A. H., Dickinson, T., Shore-Lesserson, L., Ferraris, V., Firestone, S., Kissoon, K., & Moffatt-Bruce, S. (2021). STS/SCA/AmSECT/SABM Update to the Clinical Practice Guidelines on Patient Blood Management. Annals of Thoracic Surgery, 112(3), 981-1004. https://doi.org/10.1016/j.athoracsur.2021.03.033
Turaga, A. H. (2023). The Optimal Dosing and Timing of Tranexamic Acid in Reducing Perioperative Bleeding and Transfusion Requirements in Vascular Surgery Patients: A Systematic Review. Cureus, 15(8), e43947. https://doi.org/10.7759/cureus.43947
Wesley, M. C., Pereira, L. M., Scharp, L. A., Emani, S. M., McGowan, F. X., Jr., & DiNardo, J. A. (2015). Pharmacokinetics of tranexamic acid in neonates, infants, and children undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology, 122(4), 746-758. https://doi.org/10.1097/ALN.0000000000000570
Willems, A., De Groote, F., Dumoulin, M., Fils, J. F., & Van der Linden, P. (2019). Aprotinin versus tranexamic acid in children undergoing cardiac surgery: an observational study. European Journal of Cardio-Thoracic Surgery, 56(4), 688-695. https://doi.org/10.1093/ejcts/ezz088
Zhang, Y., Gao, X., Yuan, S., Guo, J., Lv, H., Zhou, Y., Wang, Y., Ji, H., Wang, G., Li, L., & Shi, J. (2018). Effects of tranexamic acid on short-term and long-term outcomes of on-pump coronary artery bypass grafting: Randomized trial and 7-year follow-up. Cardiovascular Therapeutics, 36(6), e12472. https://doi.org/10.1111/1755-5922.12472
Zhang, Y., Jia, Y., Shi, J., Yuan, S., Wang, R., Zhang, Z., Wang, X., Liu, J., Ran, J., Zhao, Y., Hua, Z., Yan, J., Li, S., Zheng, Z., Hu, S., Wang, Y., & Yan, F. (2019). Safety and efficacy of tranexamic acid in paediatric cardiac surgery: study protocol for a double-blind randomised controlled trial. BMJ Open, 9(11), e032642. https://doi.org/10.1136/bmjopen-2019-032642
Zhang, Y., Zhang, X., Wang, Y., Shi, J., Yuan, S., Duan, F., Wang, Y., Zhang, Z., Jia, Y., Gong, J., Li, L., & Yan, F. (2019). Efficacy and Safety of Tranexamic Acid in Pediatric Patients Undergoing Cardiac Surgery: A Single-Center Experience. Front Pediatr, 7, 181. https://doi.org/10.3389/fped.2019.00181
Zonis, Z., Seear, M., Reichert, C., Sett, S., & Allen, C. (1996). The effect of preoperative tranexamic acid on blood loss after cardiac operations in children. Journal of Thoracic and Cardiovascular Surgery, 111(5), 982-987. https://doi.org/10.1016/s0022-5223(96)70374-4
Zou, Z. Y., He, L. X., & Yao, Y. T. (2022). Tranexamic acid reduces postoperative blood loss in Chinese pediatric patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore), 101(9), e28966. https://doi.org/10.1097/MD.0000000000028966
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