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

Document Type : RESEARCH PAPER


Mediclinic City Hospital, Dubai Healthcare City, Dubai, UAE


Background: This study aimed to determine whether combined intravenous (IV) and intraarticular (IA) Tranexamic
acid (TXA) reduces blood loss and the requirement of blood transfusion, compared to IA use alone in the middle eastern
patients undergoing primary cemented unilateral Total knee arthroplasty (TKA).
Methods: The present study is a double-blind randomized controlled trial (RTC) comparing the efficacy of IA alone
to combined IA and IV routes of TXA administration in patients undergoing primary cemented TKA using a tourniquet
performed by two senior surgeons. There were 21 patients in the IA alone and 29 in the combined group. The primary
outcome measure was a blood transfusion requirement, hemoglobin drop, and the total estimated blood loss on day
three postoperative period. The secondary outcomes were complications, including thromboembolic events, wound
complications, periprosthetic infection, patient-reported outcomes (PROs) of pain visual analog scale (VAS), Western
Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and EuroQol 5-dimension (EQ-5D), as well as the
range of motion (ROM), at one-year follow-up.
Results: None of the patients in either comparison group required blood transfusion in the perioperative period. The
drop in hemoglobin levels (2.1±1.0 vs. 2.2±1.1, P=0.84) and the total estimated blood loss (884±489 vs. 877±324,
P=0.96) on the third postoperative day in the IA alone group showed no statistically significant difference compared
to that in the combined group. Moreover, there were no complications noted in patients of either group. At one-year
follow-up, there was no significant difference between the two comparison groups regarding the mean PROs of pain
VAS, WOMAC, and EQ-5D, as well as ROM.
Conclusion: According to the obtained results, this RCT in the middle eastern patient population found no additional
benefit of TXA administration through combined IV and IA route over the IA alone in reducing the requirement of blood
transfusion and the total blood loss. Further similar studies with larger sample sizes are needed to ascertain the ideal
route of TXA administration in patients undergoing primary TKA.
Level of evidence: I


Main Subjects

  1. Jauregui JJ, Cherian JJ, Pierce TP, Beaver WB, Issa K, Mont MA. Long-Term Survivorship and Clinical Outcomes Following Total Knee Arthroplasty. J Arthroplasty. 2015;30(12):2164-6. doi: 10.1016/j.arth.2015.05.052.
  2. Tiwari V, Meshram P, Park CK, Bansal V, Kim TK. New mobile-bearing TKA with unique ball and socket post-cam mechanism offers similar function and stability with better prosthesis fit and gap balancing compared to an established fixed-bearing prosthesis. Knee Surg Sports Traumatol Arthrosc. 2019;27(7):2145-2154. DOI: 10.1007/s00167-019-05430-5
  3. Chen X, Ji ZL, Chen YZ. TTD: Therapeutic Target Database. Nucleic Acids Res. 2002;30(1):412-5. doi: 10.1093/nar/30.1.412.
  4. Wang H, Shen B, Zeng Y. Comparison of topical versus intravenous tranexamic acid in Primary total knee arthroplasty: a metaanalysis of randomized controlled and prospective cohort trials. Knee. 2014;21(6):987–993. doi: 10.1016/j.knee.2014.09.010.
  5. Alvarez JC, Santiveri FX, Ramos I, Vela E, Puig L, Escolano F. Tranexamic acid reduces blood transfusion in total knee arthroplasty even when a blood conservation program is applied. Transfusion. 2008;48(3):519-25. doi: 10.1111/j.1537-2995.2007.01564.x.
  6. Drain NP, Gobao VC, Bertolini DM et al. Administration of Tranexamic Acid Improves Long-Term Outcomes in Total Knee Arthroplasty. J Arthroplasty. 2020;35(6S):S201-S206. doi: 10.1016/j.arth.2020. 02.047.
  7. Kim TK, Chang CB, Koh IJ. Practical issues for the use of tranexamic acid in total knee arthroplasty: a systematic review. Knee Surg Sports Traumatol Arthrosc. 2014;22(8):1849-58. doi: 10.1007/s00167-013-2487-y.
  8. Fillingham YA, Ramkumar DB, Jevsevar DS, et al. Tranexamic acid in total joint arthroplasty: the endorsed clinical practice guides of the American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, Hip Society, and Knee Society. Reg Anesth Pain Med. 2019;44(1):7-11. doi: 10.1136/rapm-2018-000024.
  9. 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.
  10. Sun Q, Li J, Chen J, Zheng C, Liu C, Jia Y. Comparison of intravenous, topical or combined routes of tranexamic acid administration in patients undergoing total knee and hip arthroplasty: a meta-analysis of randomised controlled trials. BMJ Open. 2019;28;9(1):e024350. doi: 10.1136/bmjopen-2018-024350.
  11. Meshram P, Palanisamy JV, Seo JY, Lee JG, Kim TK. Combined Intravenous and Intraarticular Tranexamic Acid Does Not Offer Additional Benefit Compared with Intraarticular Use Alone in Bilateral TKA: A Randomized Controlled Trial. Clin Orthop Relat Res. 2020;478(1):45-54. doi: 10.1097/CORR.0000000000000942
  12. Meunier A, Petersson A, Good L, Berlin G. Validation of a haemoglobin dilution method for estimation of blood loss. Vox Sang. 2008;95:120–124. doi: 10.1111/j.1423-0410.2008.01071.x.
  13. Roos EM, Toksvig-Larsen S. Knee injury and Osteoarthritis Outcome Score (KOOS) - validation and comparison to the WOMAC in total knee replacement. Health Qual Life Outcomes. 2003;1:17. doi: 10.1186/1477-7525-1-17.
  14. EQ-5D instruments. Available at: Assessed on Apr 7, 2022
  15. Maniar RN, Kumar G, Singhi T, Nayak RM, Maniar PR. Most effective regimen of tranexamic acid in knee arthroplasty: a prospective randomized controlled study in 240 patients. Clin Orthop Relat Res. 2012;470(9):2605-2612. doi: 10.1007/s11999-012-2310-y.
  16. Sample Size Calculator, DSS research 2014. Available at Assessed 2 Jan, 2022
  17. Lee SY, Chong S, Balasubramanian D, Na YG, Kim TK. What is the ideal route of administration of tranexamic acid in TKA? A randomized controlled trial. Clin Orthop Relat Res. 2017;475:1987-1996. doi: 10.1007/s11999-017-5311-z
  18. Lin SY, Chen CH, Fu YC, Huang PJ, Chang JK, Huang HT. The efficacy of combined use of intraarticular and intravenous tranexamic acid on reducing blood loss and transfusion rate in total knee arthroplasty. J Arthroplasty. 2015;30(5):776-80. doi: 10.1016/j.arth.2014.12.001.
  19. Dorji Y, Singh CM, Mishra AK, Sad D. Efficacy of combined use of intravenous and intra-articular versus intra-articular tranexemic acid in blood loss in primary total knee arthroplasty: A randomized controlled study. JAJS. 2021;8(2) 134-138.
  20. 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 (Balti-more). 2019;98(7):e14458. doi:10.1097/MD.00000 00000014458.
  21. Fillingham YA, Ramkumar DB, Jevsevar DS, et al. The Safety of Tranexamic Acid in Total Joint Arthroplasty: A Direct Meta-Analysis. J Arthroplasty. 2018;33(10):3070-3082.e1. doi: 10.1016/j.arth. 2018.03.031.