Comparative Efficacy and Safety of Intravenous vs. Combined Intravenous and Intraarticular Tranexamic Acid Administration in Total Knee Arthroplasty: A Stratified Analysis Based on Bleeding Risk

Document Type : RESEARCH PAPER

Authors

1 The Carol Davila University of Medicine and Pharmacy, Bucharest, Romania- Department of Orthopaedics, Foisor Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, Bucharest, Romania

2 Department of Orthopaedics, Foisor Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, Bucharest, Romania

3 The Carol Davila University of Medicine and Pharmacy, Bucharest, Romania- Department of Anesthesiology and Critical Care, Foisor Clinical Hospital of Orthopaedics, Traumatology, and Osteoarticular Tuberculosis, Bucharest, Romania

4 Department of Orthopaedics, Nikan General Hospital, Tehran, Iran

5 The Carol Davila University of Medicine and Pharmacy, Bucharest, Romania- Department of Radiology and Medical Imaging, Foisor Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, Bucharest, Romania

10.22038/abjs.2025.84997.3870

Abstract

Objectives: Tranexamic acid (TXA) effectively reduces blood loss in total knee arthroplasty (TKA) without raising thromboembolism risk, though the best administration route is still debated. This study aimed to classify patients based on bleeding risk factors and determine whether intravenous (IV) alone or combined IV and intraarticular (IA) administration of TXA provides the greatest benefit.
Methods: This study included 200 patients who underwent TKA, with 100 patients with IV administration only and 100 with combined IV and IA administration. The bleeding risk stratification criteria were based on patient body mass index, age, the use of increased anticoagulant doses in patients with atrial fibrillation, and cases where synovectomy was performed. The primary outcomes measured were tube drainage volume, hemoglobin (Hb) and hematocrit (Ht) levels, and blood transfusion rates. Secondary outcomes included wound complications, symptomatic deep vein thrombosis (DVT), and symptomatic pulmonary embolism (PE).
Results: Combined IV and IA administration showed better outcomes in terms of Hb reduction (difference of 0.98 g/dl, 95%CI: 0.69 to 1.26, P<0.0001), Ht reduction (difference of 2.66%, 95% CI: 1.78 to 3.54, P<0.0001), tube drainage (294 vs 358 ml, 95% CI: 11.58 to 115.93, P=0.0170) and shorter hospitalization stay (difference of 0.53 days, 95% CI: 0.16 to 0.90, P=0.0050) compared to only IV administration. Patients who underwent synovectomy had lower tube drainage with combined TXA administration compared to IV only (355.42 ± 161.68 ml vs. 429.79 ± 268.48 ml). Neither group experienced any cases of symptomatic (i.e. DVT) or pulmonary embolism (PE).
Conclusion: The combined administration of TXA (IV and IA) in patients undergoing TKA was more effective than IV-only administration.
        Level of evidence: II

Keywords

Main Subjects

References

  1. Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020; 29-30:100587. doi:10.1016/j.eclinm.2020.100587.
  2. Arslan IG, Damen J, de Wilde M, et al. Incidence and prevalence of knee osteoarthritis using codified and narrative data from Electronic Health Records: A population‐based study. Arthritis Care Res (Hoboken). 2022; 74(6):937-944. doi: 10.1002/acr.24861.
  3. Boutsiadis A, Reynolds RJ, Saffarini M, Panisset J-C. Factors that influence blood loss and need for transfusion following total knee arthroplasty. Ann Transl Med. 2017; 5(21):418. doi: 10.21037/atm.2017.08.11.
  4. Fernandez MC, Gottlieb M, Menitove JE. Blood transfusion and postoperative infection in orthopedic patients. Transfusion. 1992; 32(4):318-322. doi:10.1046/j.1537-2995.1992.32492263444.x.
  5. Cai J, Ribkoff J, Olson S, et al. The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients. Eur J Haematol. 2020; 104(2):79-87. doi: 10.1111/ejh.13348.
  6. Dragosloveanu S, Dragosloveanu C, Petre M, Gherghe ME, Cotor DC. The impact of tourniquet usage on TKA outcome: A single-center prospective trial. Medicina (Kaunas). 2023; 59(5):870. doi: 10.3390/medicina59050870.
  7. Furqan A, Hafeez S, Khan F, Orakzai SH, Nur AN, Khan MA. Intra-articular versus intravenous tranexamic acid in primary total knee replacement. Cureus.2022; 14(1):e21052. doi: 10.7759/cureus.21052.
  8. Tranexamic acid: Uses, interactions, mechanism of action. Available at: https://go.drugbank.com/drugs/DB00302. Accessed September 20, 2024.
  9. Chen JY, Chin PL, Moo IH, et al. Intravenous versus intra-articular tranexamic acid in total knee arthroplasty: A double-blinded randomised controlled noninferiority trial. Knee. 2016; 23(1):152-6. doi: 10.1016/j.knee.2015.09.004.
  10. Wu J, Zhou Y-Q, Deng J-H, Han Y-G, Zhu Y-C, Qian Q-R. Ideal intraarticular application dose of tranexamic acid in primary total knee arthroplasty: A prospective, randomized and controlled study. Ann Transl Med. 2020; 8(21):1353. doi: 10.21037/atm-20-3064.
  11. Li J, Liu R, Rai S, Ze R, Tang X, Hong P. Intra-articular vs. intravenous administration: A meta-analysis of tranexamic acid in primary total knee arthroplasty. J Orthop Surg Res. 2020; 15(1):581. doi: 10.1186/s13018-020-02119-1.
  12. Lin ZX, Woolf SK. Safety, Efficacy, and Cost-effectiveness of Tranexamic Acid in Orthopedic Surgery. Orthopedics. 2016; 39(2):119-30. doi: 10.3928/01477447-20160301-05.
  1. Tuttle JR, Ritterman SA, Cassidy DB, Anazonwu WA, Froehlich JA, Rubin LE. Cost Benefit Analysis of Topical Tranexamic Acid in Primary Total Hip and Knee Arthroplasty. J Arthroplasty. 2014; 29(8):1512-5. doi: 10.1016/j.arth.2014.01.031.
  2. Grocott MPW, Murphy M, Roberts I, Sayers R, Toh C-H. Tranexamic acid for safer surgery: The time is now. Br J Anaesth. 2022; 129(4):459-461. doi: 10.1016/j.bja.2022.06.024.
  3. Haratian A, Shelby T, Hasan LK, Bolia IK, Weber AE, Petrigliano FA. Utilization of tranexamic acid in surgical orthopaedic practice: Indications and current considerations. Orthop Res Rev. 2021:13:187-199. doi: 10.2147/ORR.S321881.
  4. Abdulwahab T, Meshram P, Althani S, Albelooshi A. Comparison of Intraarticular Versus Combined Intravenous and Intraarticular Tranexamic Acid Administration in Patients Undergoing Primary Unilateral Total Knee Arthroplasty: A Randomized Controlled Trial in the Middle Eastern Patient Population. Arch Bone Jt Surg. 2022; 10(12):1037-1043. doi: 10.22038/ABJS.2022.67705.3210.
  5. Adravanti P, Di Salvo E, Calafiore G, Vasta S, Ampollini A, Rosa MA. A prospective, randomized, comparative study of intravenous alone and combined intravenous and intraarticular administration of tranexamic acid in primary total knee replacement. Arthroplast Today. 2017; 4(1):85-88. doi: 10.1016/j.artd.2017.08.004.
  6. Nielsen CS, Jans Ø, Ørsnes T, Foss NB, Troelsen A, Husted H. Combined Intra-Articular and Intravenous Tranexamic Acid Reduces Blood Loss in Total Knee Arthroplasty. J Bone Joint Surg Am.2016; 98(10):835-41. doi: 10.2106/JBJS.15.00810.
  7. Zhang YM, Yang B, Sun XD, Zhang Z. Combined intravenous and intra-articular tranexamic acid administration in total knee arthroplasty for preventing blood loss and hyperfibrinolysis: A randomized controlled trial. Medicine (Baltimore).2019; 98(7):e14458. doi: 10.1097/MD.0000000000014458.
  8. Mi B, Liu G, Lv H, et al. Is combined use of intravenous and intraarticular tranexamic acid superior to intravenous or intraarticular tranexamic acid alone in total knee arthroplasty? A meta-analysis of randomized controlled trials. J Orthop Surg Res.2017; 12(1):61. doi: 10.1186/s13018-017-0559-2.
  9. Yang J, Yang L, Tan J, Huo K, Zhao L, Cai D. Reduction of Blood Loss by Intra‐articular Injection of Tranexamic Acid Combined with Knee and Hip Flexion at 45° During Primary Total Knee Arthroplasty: A Randomized Controlled Trial. Orthop Surg. 2020; 12(6):1835-1842. doi: 10.1111/os.12814.
  10. Moskal J, Capps S. Intra-articular Tranexamic Acid in Primary Total Knee Arthroplasty: Meta-analysis. J Knee Surg. 2018; 31(1):56-67. doi: 10.1055/s-0037-1600092.
  11. Kleiboer B, Layer MA, Cafuir LA, et al. Postoperative bleeding complications in patients with hemophilia undergoing major orthopedic surgery: A prospective multicenter observational study. J Thromb Haemost. 2022; 20(4):857-865. doi: 10.1111/jth.15654.
  12. McQuilten ZK, Wood EM, Medcalf RL. When to use tranexamic acid for the treatment of major bleeding? J Thromb Haemost. 2024; 22(3):581-593. doi: 10.1016/j.jtha.2023.10.001.
  13. Ockerman A, Vanassche T, Garip M, et al. Tranexamic acid for the prevention and treatment of bleeding in surgery, trauma and bleeding disorders: a narrative review. Thromb J. 2021; 19(1):54. doi: 10.1186/s12959-021-00303-9.
  14. Romanian Arthroplasty Register. New: Hip biennial report 2015. Available at: https://www.rne.ro/?lang=en. Accessed September 15, 2024.
  15. Oberweis BS, Nukala S, Rosenberg A, et al. Thrombotic and bleeding complications after orthopedic surgery. Am Heart J. 2013; 165(3):427-33.e1. doi: 10.1016/j.ahj.2012.11.005.
  16. Blokhin IO, Lentz SR. Mechanisms of thrombosis in obesity. Curr Opin Hematol. 2013; 20(5):437-44. doi: 10.1097/MOH.0b013e3283634443.
  17. Braekkan SK, van der Graaf Y, Visseren FLJ, Algra A. Obesity and risk of bleeding: The smart study. J Thromb Haemost. 2016; 14(1):65-72. doi: 10.1111/jth.13184.
  18. Cao G, Chen G, Yang X, et al. Obesity does not increase blood loss or incidence of immediate postoperative complications during simultaneous total knee arthroplasty: A multicenter study. Knee.2020; 27(3):963-969. doi: 10.1016/j.knee.2020.01.012.
  19. Fernandez-Madrid F, Karvonen RL, Teitge RA, Miller PR, An T, Negendank WG. Synovial thickening detected by Mr Imaging in osteoarthritis of the knee confirmed by biopsy as synovitis. Magn Reson Imaging.1995; 13(2):177-83. doi: 10.1016/0730-725x(94)00119-n.
  20. Zhaoning X, Xu Y, Shaoqi T, Baiqiang H, Kang S. The effect of synovectomy on bleeding and clinical outcomes for total knee replacement. Bone Joint J.2013; 95-B (9):1197-200. doi: 10.1302/0301-620X.95B9.31253.
  21. Kilicarslan K, Yalcin N, Cicek H, et al. The effect of total synovectomy in total knee arthroplasty: A prospective randomized controlled study. Knee Surg Sports Traumatol Arthrosc. 2011; 19(6):932-5. doi: 10.1007/s00167-010-1270-6.
  22. Petre MA, Gherghe ME, Cotor DC, et al. The impact of total synovectomy on blood loss and knee function. A prospective randomized study. Romanian Journal of Military Medicine. 2024; 127(1):3-8. doi:10.55453/rjmm.2024.127.1.1.
  23. Zhao Z, Xu J, Wang R, Xu L. The efficacy of synovectomy for total knee arthroplasty: A meta-analysis. J Orthop Surg Res. 2018; 13(1):51. doi: 10.1186/s13018-018-0752-y.
  24. Hare GM, Mazer CD. Anemia: Perioperative risk and treatment opportunity. Anesthesiology. 2021; 135(3):520-530. doi: 10.1097/ALN.0000000000003870.
  25. Shah A, Palmer AJ, Klein AA. Strategies to minimize intraoperative blood loss during major surgery. Br J Surg. 2020; 107(2):e26-e38. doi: 10.1002/bjs.11393.
  26. Spahn DR. Anemia and patient blood management in hip and knee surgery: a systematic review of the literature. Anesthesiology.2010; 113(2):482-95. doi: 10.1097/ALN.0b013e3181e08e97.
  27. Rasouli M, Parvizi J. Tranexamic Acid in total joint arthroplasty: efficacy and safety. Arch Bone Jt Surg. 2015; 3(1):1-2.
  28. Porter SB, Spaulding AC, Duncan CM, Wilke BK, Pagnano MW, Abdel MP. Tranexamic acid was not associated with increased complications in high-risk patients with intertrochanteric fracture. J Bone Joint Surg Am. 2022; 104(13):1138-1147. doi: 10.2106/JBJS.21.01389.
  29. Enayatollahi M, Azboy I, Dietz MJ, et al. What are the contraindications, if any, for the use of tranexamic acid during knee or hip arthroplasty? J Arthroplasty. 2025; 40(2S1):S21-S24. doi: 10.1016/j.arth.2024.10.050.

 

 

 

 

The Archives of Bone and Joint Surgery
Volume 13, Issue 10
October 2025
Pages 622-630

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History

  • Receive Date: 28 December 2024
  • Revise Date: 16 February 2025
  • Accept Date: 01 March 2025

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