Letter to editor regarding “The efficacy and safety of tranexamic acid in high tibial osteotomy: a systematic review and meta-analysis”
Journal of Orthopaedic Surgery and Research volume 16, Article number: 466 (2021)
We read a recent published meta-analysis  with great interest, which entitled “The efficacy and safety of tranexamic acid in high tibial osteotomy: a systematic review and meta-analysis.” Coincidentally, with a similar analysis we did recently, we have some concerns about reported results and want to share our opinions as well.
Firstly, high heterogeneity was noticed in results of total blood loss (I2 = 91%, P < 0.00001 in Q test) between tranexamic acid (TXA) groups and control groups. A similar searching strategy was conducted up to June 7, 2021, and an extra randomized controlled trial  was included (Table 1, Fig. 1). We did meta-regression analysis by five items, including total number of patients (P = 0.605 > 0.05), age (P = 0.052 > 0.05), BMI (P = 0.575 > 0.05), preoperative hemoglobin values (P = 0.581 > 0.05), and gender (ratio of male/female, P = 0.025 < 0.05). Three subgroups were made based on gender: group 1 (> 40%), group 2 (20–40%), and group 3 (< 20%). And random-effects model was performed. Total blood loss was reduced in all three groups significantly: group 1 (I2 = 57.0%, P = 0.127; WMD = − 53.107, 95% CI [− 100.163, − 6.052], P = 0.027 < 0.05), group 2 (I2 = 0%, P = 0.751; WMD = − 362.204, 95% CI [− 423.960, − 6.052], p = < 0.05), and group 3 (WMD = − 219.471, 95% CI [− 355.615, − 83.328], p = < 0.05). Difference between subgroups was also significant (p < 0.05) (Fig. 2).
The results suggested female might benefit more than male on blood management from TXA. Some studies in arthroplasty replacement [3,4,5] and orthognathic surgeries  presented similar actions. Although the mechanism was still elusive, some hypotheses were given. Sex hormone level was suggested to have effect according to its influence on bleeding levels in hepatic surgery by protecting vascular integrity . Moreover, female might have increased risk of blood loss due to lower preoperative hemoglobin level [8, 9], and TXA had better effect in patients with higher anticipated blood loss , which led to the final effect.
Secondly, hemoglobin decrease in the TXA group was significantly lower than that in the control group on post-operation day (POD) 1, POD2, and POD5. Significant difference was also detected in drainage output on POD1 instead of POD2. Because of the short half-time of TXA (about 2 h ), we hypothesized intraoperative TXA had a short-time effect, but it might benefit patients for a relatively long time according to significant difference in hemoglobin changing value found on even 5 days after surgery while drainage output only had significant difference on POD1. Other studies also reported the strongest effect of TXA used intraoperatively occurred in the first 24 h after surgery .
Finally, analysis of some parameters (hemoglobin decrease on POD2, POD5; drainage output on POD2) were performed with random-effect model, although low risk of heterogeneity was identified (I2 < 50% and P > 0.1). We think fixed-effect model may be better choice. Authors stated it was taken after testing of publication bias; however, we did not find detailed data of it. And trim-filling analysis should be taken with existence of publication bias.
Availability of data and materials
All data generated or analyzed during this study are included in this published article.
Ma J, Lu H, Chen X, Wang D, Wang Q. The efficacy and safety of tranexamic acid in high tibial osteotomy: a systematic review and meta-analysis. J Orthop Surg Res. 2021;16(1):373. https://doi.org/10.1186/s13018-021-02512-4.
Ma Z, et al. Safety evaluation of tranexamic acid in reducing perioperative blood loss in high tibial osteotomy. [Chinese]. Chin J Tissue Eng Res. 2021;25(12):1847–52.
Dincel YM, Sarı A, Çetin MÜ, Günaydın B, Agca E, Dogan AH, et al. The effect of tranexamic acid and tourniquet use on tibial cement penetration in primary total knee arthroplasties. Arthroplast Today. 2020;6(3):422–6. https://doi.org/10.1016/j.artd.2020.04.010.
Hu Y, Li Q, Wei BG, Zhang XS, Torsha TT, Xiao J, et al. Blood loss of total knee arthroplasty in osteoarthritis: an analysis of influential factors. J Orthop Surg Res. 2018;13(1):325. https://doi.org/10.1186/s13018-018-1038-0.
Viegas R, Kumar A, Carvalho MM, Vide J, Fontes AP, Sousa JP. Impact of age, gender and body mass index on the efficacy of tranexamic acid in total knee arthroplasty. International Journal of Research in Orthopaedics. 2020;6(5):884. https://doi.org/10.18203/issn.2455-4510.IntJResOrthop20203710.
Secher JJ, Sidelmann JJ, Ingerslev J, Thorn JJ, Pinholt EM. The effect of tranexamic acid and gender on intraoperative bleeding in orthognathic surgery-a Randomized controlled trial. J Oral Maxillofac Surg. 2018;76(6):1327–33. https://doi.org/10.1016/j.joms.2017.11.015.
Yokoyama Y, Nagino M, Nimura Y. Which gender is better positioned in the process of liver surgery? Male or female? Surg Today. 2007;37(10):823–30. https://doi.org/10.1007/s00595-007-3508-6.
Danninger T, et al. Blood transfusions in total hip and knee arthroplasty: an analysis of outcomes. ScientificWorldJournal. 2014;2014:623460.
Saleh E, McClelland DBL, Hay A, Semple D, Walsh TS. Prevalence of anaemia before major joint arthroplasty and the potential impact of preoperative investigation and correction on perioperative blood transfusions. Br J Anaesth. 2007;99(6):801–8. https://doi.org/10.1093/bja/aem299.
Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military application of tranexamic acid in trauma emergency resuscitation (MATTERs) study. Arch Surg. 2012;147(2):113–9. https://doi.org/10.1001/archsurg.2011.287.
Pilbrant A, Schannong M, Vessman J. Pharmacokinetics and bioavailability of tranexamic acid. Eur J Clin Pharmacol. 1981;20(1):65–72. https://doi.org/10.1007/BF00554669.
Gausden EB, Qudsi R, Boone MD, OʼGara B, Ruzbarsky JJ, Lorich DG. Tranexamic acid in orthopaedic trauma surgery: a meta-analysis. J Orthop Trauma. 2017;31(10):513–9. https://doi.org/10.1097/BOT.0000000000000913.
Ethics approval and consent to participate
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Fang, Q., Zhang, Z., Wang, L. et al. Letter to editor regarding “The efficacy and safety of tranexamic acid in high tibial osteotomy: a systematic review and meta-analysis”. J Orthop Surg Res 16, 466 (2021). https://doi.org/10.1186/s13018-021-02616-x