Skip to main content
Top
Published in: BMC Musculoskeletal Disorders 1/2024

Open Access 01-12-2024 | Ankle Fracture | Research

The efficacy and safety of different does of intravenous tranexamic acid on blood loss in fresh foot and ankle fractures: a prospective, randomized controlled study

Authors: Gang Tan, Jia Li, Jing Xu, Yongzhan Zhu, Hui Zhang

Published in: BMC Musculoskeletal Disorders | Issue 1/2024

Login to get access

Abstract

Background

There are a few studies on the effectiveness and safety of intravenous administration of tranexamic acid(TXA) in patients who underwent foot and ankle surgery, especially for preoperative hidden blood loss in patients with freshfoot and ankle fractures. Thus, the aim of this study was to investigate whether intravenous administration of different doses of TXA can effectively reduce perioperative blood loss and blood loss before surgery and to determine its safety.

Methods

A total of 150 patients with fresh closed foot and ankle fractures from July 2021 to July 2023 were randomly divided into a control group (placebo controlled [PC]), standard-dose group (low-dose group [LD], 1 g/24 h; medium-dose group [MD], 2 g/24 h), and high-dose group (HD, 3 g/24 h; ultrahigh-dose group [UD], 4 g/24 h). After admission, all patients completed hematological examinations as soon as possible and at multiple other time points postsurgery.

Results

There was a significant difference in the incidence of hidden blood loss before the operation between the TXA group and the control group, and the effect was greater in the overdose groups than in the standard-dose groups. There were significant differences in surgical blood loss (intraoperative and postoperative), postoperative HGB changes, and hidden blood loss among the groups. The TXA groups showed a significant decrease in blood loss compared to that of the control group, and the overdose groups had a more significant effect than the standard-dose groups. A total of 9 patients in the control group had early wound infection or poor healing, while only 1 patient in the other groups had this complication, and the difference among the groups was significant. No patients in any group suffered from late deep wound infection, cardiovascular or cerebrovascular events or symptomatic VTE.

Conclusion

This is the first study on whether TXA can reduce preoperative hidden blood loss in patients with freshfoot and ankle fractures. In our study, on the one hand, intravenous application of TXA after foot and ankle fractures as soon as possible can reduce preoperative blood loss and postoperative blood loss. On the other hand, TXA can also lower wound complications, and over-doses of TXA are more effective than standard doses. Moreover, overdoses of TXA do not increase the incidence of DVT.
Literature
1.
go back to reference Kottmeier SA, Madison RD, Divaris N. Pilon fracture: preventing complications [J]. J Am Acad Orthop Surg. 2018;26(18):640–51.CrossRefPubMed Kottmeier SA, Madison RD, Divaris N. Pilon fracture: preventing complications [J]. J Am Acad Orthop Surg. 2018;26(18):640–51.CrossRefPubMed
2.
go back to reference Heyns M, Knight P, Steve AK, et al. A single preoperative dose of Tranexamic Acid reduces Perioperative Blood loss: a Meta-analysis [J]. Ann Surg. 2021;273(1):75–81.CrossRefPubMed Heyns M, Knight P, Steve AK, et al. A single preoperative dose of Tranexamic Acid reduces Perioperative Blood loss: a Meta-analysis [J]. Ann Surg. 2021;273(1):75–81.CrossRefPubMed
3.
go back to reference CRASH-2 collaborators, Roberts I, Shakur H, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial [J]. Lancet. 2011;377(9771):1096–e110111012.CrossRef CRASH-2 collaborators, Roberts I, Shakur H, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial [J]. Lancet. 2011;377(9771):1096–e110111012.CrossRef
4.
go back to reference Xiong Z, Wu K, Zhang J, et al. Different dose regimens of Intravenous Tranexamic Acid in adolescent spinal deformity surgery: a systematic review and Meta-analysis [J]. Biomed Res Int. 2020;2020:3101358.CrossRefPubMedPubMedCentral Xiong Z, Wu K, Zhang J, et al. Different dose regimens of Intravenous Tranexamic Acid in adolescent spinal deformity surgery: a systematic review and Meta-analysis [J]. Biomed Res Int. 2020;2020:3101358.CrossRefPubMedPubMedCentral
5.
go back to reference Taeuber I, Weibel S, Herrmann E, et al. Association of Intravenous Tranexamic Acid with thromboembolic events and mortality: a systematic review, Meta-analysis, and Meta-regression [J]. JAMA Surg. 2021;156(6):e210884.CrossRefPubMedPubMedCentral Taeuber I, Weibel S, Herrmann E, et al. Association of Intravenous Tranexamic Acid with thromboembolic events and mortality: a systematic review, Meta-analysis, and Meta-regression [J]. JAMA Surg. 2021;156(6):e210884.CrossRefPubMedPubMedCentral
6.
go back to reference Ker K, Edwards P, Perel P, et al. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis [J]. BMJ. 2012;344:e3054.CrossRefPubMedPubMedCentral Ker K, Edwards P, Perel P, et al. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis [J]. BMJ. 2012;344:e3054.CrossRefPubMedPubMedCentral
7.
go back to reference Thorne JG, James PD, Reid RL. Heavy menstrual bleeding: is tranexamic acid a safe adjunct to combined hormonal contraception? [J]. Contraception. 2018;98(1):1–3.CrossRefPubMed Thorne JG, James PD, Reid RL. Heavy menstrual bleeding: is tranexamic acid a safe adjunct to combined hormonal contraception? [J]. Contraception. 2018;98(1):1–3.CrossRefPubMed
8.
go back to reference Weng S, Wang W, Wei Q, et al. Effect of Tranexamic Acid in patients with traumatic Brain Injury: a systematic review and Meta-analysis [J]. World Neurosurg. 2019;123:128–35.CrossRefPubMed Weng S, Wang W, Wei Q, et al. Effect of Tranexamic Acid in patients with traumatic Brain Injury: a systematic review and Meta-analysis [J]. World Neurosurg. 2019;123:128–35.CrossRefPubMed
9.
go back to reference Brown NJ, Choi EH, Gendreau JL, et al. Association of tranexamic acid with decreased blood loss in patients undergoing laminectomy and fusion with posterior instrumentation: a systematic review and meta-analysis [J]. J Neurosurg Spine. 2021;36(4):686–93.CrossRefPubMed Brown NJ, Choi EH, Gendreau JL, et al. Association of tranexamic acid with decreased blood loss in patients undergoing laminectomy and fusion with posterior instrumentation: a systematic review and meta-analysis [J]. J Neurosurg Spine. 2021;36(4):686–93.CrossRefPubMed
10.
go back to reference July J, Pranata R. Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury - meta-analysis of randomized controlled trials [J]. BMC Neurol. 2020;20(1):119.CrossRefPubMedPubMedCentral July J, Pranata R. Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury - meta-analysis of randomized controlled trials [J]. BMC Neurol. 2020;20(1):119.CrossRefPubMedPubMedCentral
11.
go back to reference Gong M, Liu G, Chen L, et al. The efficacy and safety of Intravenous Tranexamic Acid in reducing Surgical Blood loss in posterior lumbar Interbody Fusion for the adult: a systematic review and a Meta-analysis [J]. World Neurosurg. 2019;122:559–68.CrossRefPubMed Gong M, Liu G, Chen L, et al. The efficacy and safety of Intravenous Tranexamic Acid in reducing Surgical Blood loss in posterior lumbar Interbody Fusion for the adult: a systematic review and a Meta-analysis [J]. World Neurosurg. 2019;122:559–68.CrossRefPubMed
12.
go back to reference Hmidan Simsam M, Delorme L, Grimm D, et al. Efficacy of high dose tranexamic acid (TXA) for hemorrhage: a systematic review and meta-analysis [J]. Injury. 2023;54(3):857–70.CrossRefPubMed Hmidan Simsam M, Delorme L, Grimm D, et al. Efficacy of high dose tranexamic acid (TXA) for hemorrhage: a systematic review and meta-analysis [J]. Injury. 2023;54(3):857–70.CrossRefPubMed
13.
go back to reference Chornenki NLJ, Um KJ, Mendoza PA, et al. Risk of venous and arterial thrombosis in non-surgical patients receiving systemic tranexamic acid: a systematic review and meta-analysis [J]. Thromb Res. 2019;179:81–6.CrossRefPubMed Chornenki NLJ, Um KJ, Mendoza PA, et al. Risk of venous and arterial thrombosis in non-surgical patients receiving systemic tranexamic acid: a systematic review and meta-analysis [J]. Thromb Res. 2019;179:81–6.CrossRefPubMed
14.
go back to reference Nadler SB, Hidalgo JH, Bloch T. Prediction of blood volume in normal human adults. Surg [J]. 1962;51(2):224–32. Nadler SB, Hidalgo JH, Bloch T. Prediction of blood volume in normal human adults. Surg [J]. 1962;51(2):224–32.
15.
go back to reference Gross JB. Estimating allowable blood loss: corrected for dilution [J]. Anesthesiology. 1983;58(3):277–80.CrossRefPubMed Gross JB. Estimating allowable blood loss: corrected for dilution [J]. Anesthesiology. 1983;58(3):277–80.CrossRefPubMed
16.
go back to reference Ma H, Wang H, Long X, et al. Early intravenous tranexamic acid intervention reduces post-traumatic hidden blood loss in elderly patients with intertrochanteric fracture: a randomized controlled trial [J]. J Orthop Surg Res. 2021;16(1):106.CrossRefPubMedPubMedCentral Ma H, Wang H, Long X, et al. Early intravenous tranexamic acid intervention reduces post-traumatic hidden blood loss in elderly patients with intertrochanteric fracture: a randomized controlled trial [J]. J Orthop Surg Res. 2021;16(1):106.CrossRefPubMedPubMedCentral
17.
go back to reference Charoencholvanich K, Siriwattanasakul P. Tranexamic acid reduces blood loss and blood transfusion after TKA: a prospective randomized controlled trial [J]. Clin Orthop Relat Res. 2011;469(10):2874–80.CrossRefPubMedPubMedCentral Charoencholvanich K, Siriwattanasakul P. Tranexamic acid reduces blood loss and blood transfusion after TKA: a prospective randomized controlled trial [J]. Clin Orthop Relat Res. 2011;469(10):2874–80.CrossRefPubMedPubMedCentral
18.
go back to reference Kim TK, Chang CB, Kang YG, et al. Clinical value of tranexamic acid in unilateral and simultaneous bilateral TKAs under a contemporary blood-saving protocol: a randomized controlled trial [J]. Knee Surg Sports Traumatol Arthrosc. 2014;22(8):1870–8.CrossRefPubMed Kim TK, Chang CB, Kang YG, et al. Clinical value of tranexamic acid in unilateral and simultaneous bilateral TKAs under a contemporary blood-saving protocol: a randomized controlled trial [J]. Knee Surg Sports Traumatol Arthrosc. 2014;22(8):1870–8.CrossRefPubMed
19.
go back to reference Wang CG, Sun ZH, Liu J, et al. Safety and efficacy of intra-articular tranexamic acid injection without drainage on blood loss in total knee arthroplasty: a randomized clinical trial [J]. Int J Surg. 2015;20:1–7.CrossRefPubMed Wang CG, Sun ZH, Liu J, et al. Safety and efficacy of intra-articular tranexamic acid injection without drainage on blood loss in total knee arthroplasty: a randomized clinical trial [J]. Int J Surg. 2015;20:1–7.CrossRefPubMed
20.
go back to reference CRASH-2 trial collaborators, Shakur H, Roberts I, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial [J]. Lancet. 2010;376(9734):23–32.CrossRef CRASH-2 trial collaborators, Shakur H, Roberts I, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial [J]. Lancet. 2010;376(9734):23–32.CrossRef
21.
go back to reference Yang ZG, Chen WP, Wu LD. Effectiveness and safety of tranexamic acid in reducing blood loss in total knee arthroplasty: a meta-analysis [J]. J Bone Joint Surg Am. 2012;94(13):1153–9.CrossRefPubMed Yang ZG, Chen WP, Wu LD. Effectiveness and safety of tranexamic acid in reducing blood loss in total knee arthroplasty: a meta-analysis [J]. J Bone Joint Surg Am. 2012;94(13):1153–9.CrossRefPubMed
22.
go back to reference Konig G, Hamlin BR, Waters JH. Topical tranexamic acid reduces blood loss and transfusion rates in total hip and total knee arthroplasty [J]. J Arthroplasty. 2013;28(9):1473–6.CrossRefPubMed Konig G, Hamlin BR, Waters JH. Topical tranexamic acid reduces blood loss and transfusion rates in total hip and total knee arthroplasty [J]. J Arthroplasty. 2013;28(9):1473–6.CrossRefPubMed
23.
go back to reference Yazdi H, Klement MR, Hammad M, et al. Tranexamic acid is Associated with reduced periprosthetic joint infection after primary total joint arthroplasty [J]. J Arthroplasty. 2020;35(3):840–4.CrossRefPubMed Yazdi H, Klement MR, Hammad M, et al. Tranexamic acid is Associated with reduced periprosthetic joint infection after primary total joint arthroplasty [J]. J Arthroplasty. 2020;35(3):840–4.CrossRefPubMed
24.
go back to reference Karaaslan F, Karaoğlu S, Yurdakul E. Reducing Intra-articular Hemarthrosis after Arthroscopic Anterior Cruciate Ligament Reconstruction by the Administration of Intravenous Tranexamic Acid: a prospective, randomized controlled trial [J]. Am J Sports Med. 2015;43(11):2720–6.CrossRefPubMed Karaaslan F, Karaoğlu S, Yurdakul E. Reducing Intra-articular Hemarthrosis after Arthroscopic Anterior Cruciate Ligament Reconstruction by the Administration of Intravenous Tranexamic Acid: a prospective, randomized controlled trial [J]. Am J Sports Med. 2015;43(11):2720–6.CrossRefPubMed
25.
go back to reference Jiang W, Shang L. Tranexamic acid can reduce blood loss in patients undergoing intertrochanteric fracture surgery: a meta-analysis [J]. Med (Baltim). 2019;98(11):e14564.CrossRef Jiang W, Shang L. Tranexamic acid can reduce blood loss in patients undergoing intertrochanteric fracture surgery: a meta-analysis [J]. Med (Baltim). 2019;98(11):e14564.CrossRef
26.
go back to reference Tian S, Shen Z, Liu Y, et al. The effect of tranexamic acid on hidden bleeding in older intertrochanteric fracture patients treated with PFNA [J]. Injury. 2018;49(3):680–4.CrossRefPubMed Tian S, Shen Z, Liu Y, et al. The effect of tranexamic acid on hidden bleeding in older intertrochanteric fracture patients treated with PFNA [J]. Injury. 2018;49(3):680–4.CrossRefPubMed
27.
go back to reference Wang Z, Lu Y, Wang Q, et al. Comparison of the effectiveness and safety of intravenous and topical regimens of tranexamic acid in complex tibial plateau fracture: a retrospective study [J]. BMC Musculoskelet Disord. 2020;21(1):739.CrossRefPubMedPubMedCentral Wang Z, Lu Y, Wang Q, et al. Comparison of the effectiveness and safety of intravenous and topical regimens of tranexamic acid in complex tibial plateau fracture: a retrospective study [J]. BMC Musculoskelet Disord. 2020;21(1):739.CrossRefPubMedPubMedCentral
28.
go back to reference Lei T, Bingtao W, Zhaoqing G, et al. The efficacy and safety of intravenous tranexamic acid in patients with posterior operation of multilevel thoracic spine stenosis: a prospective randomized controlled trial [J]. BMC Musculoskelet Disord. 2022;23(1):410.CrossRefPubMedPubMedCentral Lei T, Bingtao W, Zhaoqing G, et al. The efficacy and safety of intravenous tranexamic acid in patients with posterior operation of multilevel thoracic spine stenosis: a prospective randomized controlled trial [J]. BMC Musculoskelet Disord. 2022;23(1):410.CrossRefPubMedPubMedCentral
29.
go back to reference Li J, Wang L, Bai T, et al. Combined use of intravenous and topical tranexamic acid efficiently reduces blood loss in patients aged over 60 operated with a 2-level lumbar fusion [J]. J Orthop Surg Res. 2020;15(1):339.CrossRefPubMedPubMedCentral Li J, Wang L, Bai T, et al. Combined use of intravenous and topical tranexamic acid efficiently reduces blood loss in patients aged over 60 operated with a 2-level lumbar fusion [J]. J Orthop Surg Res. 2020;15(1):339.CrossRefPubMedPubMedCentral
31.
go back to reference Salameh M, Attia AK, El Khatib S, et al. Tranexamic acid utilization in foot and ankle surgery: a Meta-analysis [J]. Foot Ankle Int. 2022;43(10):1370–8.CrossRefPubMed Salameh M, Attia AK, El Khatib S, et al. Tranexamic acid utilization in foot and ankle surgery: a Meta-analysis [J]. Foot Ankle Int. 2022;43(10):1370–8.CrossRefPubMed
32.
go back to reference Tang X, Li K, Zheng F, et al. The effect of perioperative tranexamic acid (TXA) in patients with calcaneal fractures: a meta-analysis and systematic review of randomized controlled trials [J]. J Orthop Surg Res. 2023;18(1):495.CrossRefPubMedPubMedCentral Tang X, Li K, Zheng F, et al. The effect of perioperative tranexamic acid (TXA) in patients with calcaneal fractures: a meta-analysis and systematic review of randomized controlled trials [J]. J Orthop Surg Res. 2023;18(1):495.CrossRefPubMedPubMedCentral
33.
go back to reference Moore AD, Smith BR, O’Leary RJ, et al. Tranexamic Acid Associated with Less Wound complications in Ankle and Hindfoot surgery: Level III, Retrospective Cohort Study [J]. J Am Acad Orthop Surg. 2022;30(16):789–97.CrossRefPubMed Moore AD, Smith BR, O’Leary RJ, et al. Tranexamic Acid Associated with Less Wound complications in Ankle and Hindfoot surgery: Level III, Retrospective Cohort Study [J]. J Am Acad Orthop Surg. 2022;30(16):789–97.CrossRefPubMed
35.
go back to reference Diskina BHPP, Lin D. Use of tranexamic acid does not influence perioperative outcomes in ambulatory foot and ankle surgery-a prospective triple blinded randomized controlled trial [J]. Int Orthop. 2021;45(9):2277–84.CrossRefPubMed Diskina BHPP, Lin D. Use of tranexamic acid does not influence perioperative outcomes in ambulatory foot and ankle surgery-a prospective triple blinded randomized controlled trial [J]. Int Orthop. 2021;45(9):2277–84.CrossRefPubMed
36.
go back to reference Steinmetz RG, Luick L, Tkach S, et al. Effect of Tranexamic Acid on Wound complications and Blood loss in total ankle arthroplasty [J]. Foot Ankle Int. 2020;41(9):1117–21.CrossRefPubMed Steinmetz RG, Luick L, Tkach S, et al. Effect of Tranexamic Acid on Wound complications and Blood loss in total ankle arthroplasty [J]. Foot Ankle Int. 2020;41(9):1117–21.CrossRefPubMed
37.
go back to reference Syrovets T, LuJuly O, Simmet T. Plasmin as a proinflammatory cell activator [J]. J Leukoc Biol. 2012;92(3):509–19.CrossRefPubMed Syrovets T, LuJuly O, Simmet T. Plasmin as a proinflammatory cell activator [J]. J Leukoc Biol. 2012;92(3):509–19.CrossRefPubMed
38.
go back to reference Prudovsky I, Kacer D, Zucco VV, et al. Tranexamic acid: beyond antifibrinolysis [J]. Transfusion. 2022;62(Suppl 1):S301–12.PubMed Prudovsky I, Kacer D, Zucco VV, et al. Tranexamic acid: beyond antifibrinolysis [J]. Transfusion. 2022;62(Suppl 1):S301–12.PubMed
39.
go back to reference Lei YT, Xie JW, Huang Q, et al. The antifibrinolytic and anti-inflammatory effects of a high initial-dose tranexamic acid in total knee arthroplasty: a randomized controlled trial [J]. Int Orthop. 2020;44(3):477–86.CrossRefPubMed Lei YT, Xie JW, Huang Q, et al. The antifibrinolytic and anti-inflammatory effects of a high initial-dose tranexamic acid in total knee arthroplasty: a randomized controlled trial [J]. Int Orthop. 2020;44(3):477–86.CrossRefPubMed
Metadata
Title
The efficacy and safety of different does of intravenous tranexamic acid on blood loss in fresh foot and ankle fractures: a prospective, randomized controlled study
Authors
Gang Tan
Jia Li
Jing Xu
Yongzhan Zhu
Hui Zhang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2024
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-024-07410-4

Other articles of this Issue 1/2024

BMC Musculoskeletal Disorders 1/2024 Go to the issue