Abstract
Posterior lumbar interbody fusion requires stripping the multifidus muscle, destroying a large amount of cancellous bone and damaging the posterior spinal venous plexus. Typically, surgical trauma is extensive, the surgical duration is long, and the degree of bleeding is substantial. Excessive blood loss can compromise a patient's hemodynamic stability, elevate surgical risks, and cause damage to vital organs, potentially becoming life-threatening in severe cases. Tranexamic acid (TXA) is a lysine derivative that can inhibit fibrinolysis, reduce D-dimer production, and reduce inflammation. In this review, we discuss the application of and research progress on TXA regarding its mechanism of action, mode of administration, timing, dose, safety, and economic benefits. The primary purpose of this review is to provide an essential reference for the administration of TXA during posterior lumbar interbody fusion surgery as well as a reference for future research.
1 Introduction
Perioperative blood management refers to the use of multiple techniques for blood protection at various stages of the perioperative period (). The primary purposes of blood management are to reduce blood loss, blood transfusion rates, and complication rates as well as to improve surgical safety and increase patient satisfaction (). In the field of spinal surgery, lumbar degenerative diseases account for the majority of diseases requiring posterior lumbar interbody fusion (, ). In the past, lumbar degenerative diseases were reported to occur mainly among middle-aged and elderly individuals. In recent years, with the aging of the population and changes in people's lifestyles, the incidence of lumbar degenerative diseases has increased annually, and the age at onset has shown a decreasing trend. Minimally invasive spine surgery can expose the surgical field of vision and can reduce local tissue damage as well as vascular and nerve damage. Furthermore, minimally invasive spine surgery does not require the extensive stripping of muscles, and this technique can retain most of the bone structure and ligament structure (). According, minimally invasive spine surgery has many advantages. For example, it is beneficial for maintaining the stability of the spine and the nutrition of blood vessels and nerves to the muscles. After minimally invasive spine surgery, postoperative lumbar function recovery is fast. Furthermore, degree of bleeding is low, the low back pain symptoms are mild, and the hospitalization time is short (, , ). Due to these advantages, minimally invasive spinal surgery is favored by both doctors and patients (, ). However, there are many limitations associated with the surgical indications for minimally invasive spine surgery (). Therefore, posterior lumbar interbody fusion is still the mainstream surgical method for treating lumbar degenerative diseases (, ).
The amount of perioperative blood loss among patients requiring posterior lumbar interbody fusion ranges from 670 to 2570 ml (), and hidden blood loss accounts for ~42%−47% of the total blood loss (, ). When no blood loss prevention measures are implemented, the blood transfusion rate ranges from 50 to 81% (). This large amount of blood loss increases not only the blood transfusion rate but also the infection and complication rates. Moreover, a large amount of blood loss causes changes in patient hemodynamics, thereby affecting the supply of blood to essential organs (). If substantial blood loss is not treated in time or is improperly controlled, adverse symptoms (such as anemia) may occur, thus affecting the patient's postoperative rehabilitation, quality of life, and prognosis; increasing medical costs; and prolonging hospital stays. In severe cases of blood loss, haemorrhagic shock or even death may occur (). In addition, blood transfusion may present many risks, such as transfusion reactions, haemolytic reactions, fever, infection, postoperative spinal epidural haematoma formation, acute lung injury, and transfusion-related infectious diseases (). Furthermore, many previous studies have shown that allogeneic blood transfusion increases the risk of postoperative infection (), and the lack of blood management resources and high medical expenses have become considerable social burdens. Therefore, optimizing blood management strategies, effectively controlling perioperative bleeding, and reducing blood transfusions have become clinical problems that spinal surgeons urgently need to solve.
To this end, some studies have evaluated the role of patient blood management strategies in intraoperative bleeding and postoperative blood loss during posterior lumbar interbody fusion, including avoiding abdominal compression, controlling hypotension, bipolar coagulation haemostasis, local anesthesia, autologous blood transfusion, haemodilution, intraoperative blood recovery, and the use of iron and erythropoietin (, , ). These measures are only sometimes effective solutions to the problem of perioperative bleeding in posterior lumbar interbody fusion (). In addition, tranexamic acid (TXA) is a lysine derivative that can stabilize the structure of fibrin and reduce the incidence of bleeding secondary to hyperfibrinolysis (). Furthermore, TXA can also reduce the formation of D-dimers (, ), and reduce inflammatory responses (–). Therefore, TXA is also widely used as a blood management strategy in spinal surgery (, ). In this review, the mechanism of action, optimal mode of administration, optimal timing of administration, optimal dose of administration, safety, complications, and economic benefits of TXA during posterior lumbar interbody fusion were discussed.
2 Posterior lumbar interbody fusion results in increased blood loss
Posterior lumbar interbody fusion is considered one of the ten significant operations requiring blood transfusion due to the incidence of considerable perioperative blood loss (). Among these operation, lumbar spinal stenosis and lumbar spondylolisthesis are the most common procedures for posterior lumbar interbody fusion in patients with lumbar degenerative diseases. Posterior lumbar interbody fusion is different from spinal orthopedic surgery. In spinal orthopedic surgery, the primary source of blood loss is only exposed bone surface blood loss. However, in posterior lumbar interbody fusion, the source of blood loss is multifaceted and multifactorial. For example, the complex anatomy of the spine and its rich blood supply, well-fed cancellous bone, and enhanced fibrinolytic activity resulting from surgery may lead to blood loss (). In addition, patients with lumbar spinal stenosis and/or lumbar spondylolisthesis have a more abundant posterior spinal venous plexus (). Posterior lumbar interbody fusion makes it difficult to avoid injury to the venous plexus, and the fragile venous plexus cannot contract after damage. An injured venous plexus often leads to difficulty in haemostasis and increased blood loss (). Moreover, the fibrinolytic response induced by surgical trauma tends to intensify with prolonged operation duration, resulting in increased fibrinolytic hyperfunction. The results of Xie et al. () and Blanié et al. () indicated that the fibrinolytic effect triggered by surgical trauma peaks at 6 h after surgery and persists for a minimum of 24 h. In conclusion, increased fibrinolytic activity, extensive destruction of cancellous bone, and injury to the posterior spinal venous plexus during posterior lumbar interbody fusion are the primary contributors to perioperative bleeding.
3 The mechanism of action of TXA
TXA is a synthetic lysine derivative that was first described in the 1970s. TXA can reversibly and competitively adsorb the lysine binding site (LBS) of the fibrin affinity site on plasmin and plasminogen and form a reversible complex with it. TXA can reduce the conversion of plasminogen to active plasmin, thereby stabilizing the structure of fibrin, reducing the breakdown rate of fibrinogen, and reducing the degree of bleeding secondary to hyperfibrinolysis (, ) (Figure 1). In addition, abnormally hyperactive fibrinolytic enzymes inhibit platelet aggregation and decompose coagulation factors; therefore, TXA also has a protective effect on platelets and coagulation factors (). In addition, TXA can also achieve antiallergic and anti-inflammatory effects by inhibiting vascular permeability, allergic reactions, and the production of kinin as well as other active peptides in inflammatory lesions (–). TXA is similar to the antifibrinolytic drug ε-aminocaproic acid (EACA); however, TXA exhibits more efficient and long-lasting antifibrinolytic activity in tissues than EACA. The effect of TXA is 6–10 times stronger than that of EACA and 4–6 times stronger than that of amino-toluic acid (). In a study by Li et al. (), the efficacy of TXA was compared with that of aprotinin and EACA among 943 patients who underwent spinal surgery. The findings revealed that all antifibrinolytic drugs can reduce perioperative blood loss and reduce the need for blood transfusions. However, TXA was more effective than aprotinin or EACA. In addition, Li et al. () also reported that TXA can reduce intraoperative blood loss by 53%, reduce postoperative blood loss by 20%, and reduce transfusion volume by 62%.
Figure 1
TXA is metabolized by the kidney and has a half-life of ~80–120 min, reaching a peak plasma concentration after 60 min of intravenous infusion. Approximately 30%−55% of TXA is excreted through the kidney 1–3 h after administration, and ~76%−90% of TXA is excreted through the kidneys in its original form through the urine within 24 h of administration (
4 The clinical application of TXA
TXA, a haemostatic agent, has gained widespread approval and clinical use after the ongoing controversy related to aprotinin, which was initially discontinued in 2007 (
4.1 The mode of TXA administration
The application of TXA in total knee arthroplasty has been very mature, including intravenous administration (
Some previous studies have shown that (
4.2 Timing and dosage of TXA administration
TXA is considered to be effective in terms of reducing perioperative blood loss. However, it remains unclear whether TXA is routinely used in posterior lumbar interbody fusion. Furthermore, the optimal timing and dosage of TXA administration remain unclear. The fibrinolytic system is activated by surgical trauma. Fibrinolytic activation is a cascade reaction process. Therefore, choosing the appropriate timing for TXA administration is important. Most scholars believe that TXA should be used before fibrinolytic activation (
Related studies have shown that the half-life of TXA is ~2 h, and the effective plasma concentration is 1 μg/ml. After an intravenous infusion of 15 mg/kg, TXA exerts the strongest effects within the first 16 h after administration (
To better determine the optimal dose of TXA, Brown et al. (
5 Safety and complications of TXA
The application of TXA during spinal surgery has been extensively studied. However, up to now, TXA is not routinely used in China. Because of the lack of high-quality, large-sample, multicenter clinical research articles and the lack of statistical analyses of previously reported studies, there are safety concerns with respect to TXA. These safety concerns include an increased incidence of thromboembolic events [such as pulmonary embolism (PE), deep vein thrombosis (DVT), and myocardial infarction (MI)] as well as increased incidence of epilepsy that can occur due to a single moderate or high dose of TXA (
To confirm the safety of TXA, Yuan et al. (
Table 1
| Complication | Number of trials (n) | Weighted event rates | RR (95% CI) | I2 | |
|---|---|---|---|---|---|
| TXA | No TXA | ||||
| DVT | 8 (46,630) | 0.28% | 0.29% | 0.97 (0.69–1.37) | 0% |
| PE | 6 (43,161) | 0.52% | 0.54% | 0.97 (0.75–1.26) | 0% |
| MI | 3 (42,470) | 0.27% | 0.30% | 0.88 (0.43–1.84) | 46% |
| Stroke | 5 (42,815) | 0.45% | 0.41% | 1.10 (0.68–1.78) | 31% |
Systematic review of 22 RCTs (including CRASH-2 and WOMAN).
DVT, Deep vein thrombosis; PE, Pulmonary embolism; MI, Myocardial infarction.
However, when it is administered via intravenous injection, TXA can penetrate the blood-brain barrier and affect the central nervous system (CNS) and the eyes. The concentration of TXA in cerebrospinal fluid and aqueous humor is ~10% of its concentration in plasma (
Larger doses of TXA can also cause non-ischemic seizures. When glycine (Gly) binds to the Gly receptor, it does not induce seizures (Figure 2A). TXA competitively binds to glycine receptors and inhibits their activation, thereby increasing muscle excitability and leading to non-ischemic seizures (
Figure 2

(A–C) Diagram of TXA causing seizures. TXA binds to the glycine receptors, resulting in a decrease in inhibitory current. This reduction in anion conduction increases excitability, which gives rise to seizures. Anesthetics reverse the effect of TXA by increasing glycine receptor function and thereby prevent or reverse TXA-induced seizures. TXA, tranexamic acid.
6 The economic benefits of TXA
To better clarify the economic benefits of TXA, a previous study conducted a statistical analysis of patients who underwent total hip arthroplasty. TXA was found to result to savings of at least $128 per patient and up to ~$600 among patients undergoing revision surgery (69). Similarly, Ehresman et al. (70) analyzed data from 1,353 patients who underwent lumbar fusion surgery and reported that TXA led to savings of ~$328.69 per patient and resulted in fewer allogeneic blood transfusions during hospitalization. Due to the considerable blood loss that occurs after posterior lumbar interbody fusion, patients often need blood products (
7 Conclusion and future prospects
During the perioperative period of posterior lumbar interbody fusion, doctors usually need to consider blood conservation strategies for patients. Intravenous use of TXA during perioperative period can reduce blood loss in patients without increasing the incidence of thromboembolic events (
Table 2
| Study | Research object | Groups | Conclusion |
|---|---|---|---|
| Hui et al., 2021 ( | Cervical, thoracic, and lumbar spinal surgery patients | Topical use of TXA vs. Control group | Topical use of TXA in spinal surgery can reduce blood loss |
| Mu et al., 2018 ( | Double-segment posterior lumbar interbody fusion (PLIF) | Intravenous administration group vs. topical administration group vs. placebo group | TXA can reduce blood loss, extubation time, and the length of hospital stay. In addition, intravenous administration can minimize blood loss more efficiently |
| Cao et al., 2022 ( | Patients undergoing spinal surgery | Intravenous plus topical administration of TXA vs. topical administration vs. placebo group | Effect of reducing blood loss: intravenous plus topical administration > topical administration > Placebo group |
| Abdou et al., 2022 ( | interbody fusion (PLIF) | Intravenous infusion of 10 mg/kg for 20 min after induction of anesthesia + the maintenance dose of 1 mg/kg/h vs. no receive TXA | Low-dose TXA has no effect on the reduction of intraoperative blood loss volume or blood transfusion requirements. However, it can significantly reduce the need for postoperative blood transfusion requirements |
| Tsutsumimoto et al., 2011 ( | “French-door” cervical laminoplasty from C3 to C6 was performed | Patients received 15 mg/kg body weight of TXA before the skin incision was made vs. placebo group | Intravenous infusion of TXA can significantly reduce the amount of bleeding in the first 16 h after surgery (~37% reduction) |
| Hui et al., 2018 ( | Spinal surgeries: A meta-analysis | High-dose TXA (10–100 mg/kg) vs. low-dose TXA (<10 mg/kg) | High-dose TXA significantly reduces intraoperative-perioperative allogeneic transfusion rates and operative time |
| Brown et al., 2022 ( | Cervical, thoracic, and lumbar laminectomy and fusion | A total of 411 patients from 11 relevant clinical studies were analyzed | The most common route of administration, timing, and dose of TXA was preoperative intravenous injection at a dose of 15 mg/kg |
| Lin et al., 2016 ( | TXA associated seizures | 26,079 patients with TXA exposure vs. 7,395 patients without TXA exposure | The prevalence of TXA-induced epilepsy was 2.7%, and this rate increased as the TXA dose increased |
| Cheriyan et al., 2015 ( | Efficacy of TXA on surgical bleeding in spine surgery | Intravenous TXA vs. placebo group | Intravenous injection of TXA at a dose of 10–15 mg/kg or 1 g is sufficient, and a higher dose does not yield additional haemostatic benefits but does increase the risk of epilepsy |
Major studies on the mode of administration, timing, and dosage of TXA.
Statements
Author contributions
WD: Conceptualization, Writing – original draft. YT: Writing – original draft, Conceptualization. YZ: Writing – original draft, Visualization. JL: Writing – original draft, Visualization. CW: Writing – original draft, Visualization. YL: Visualization, Writing – original draft. YY: Writing – original draft, Visualization. ZP: Supervision, Writing – review & editing. JZ: Supervision, Writing – review & editing.
Funding
The author(s) declare that financial support was received for the research and/or publication of this article. Natural Science Foundation of Chongqing Yuzhong District (No. 20240137).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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The author(s) declare that no Gen AI was used in the creation of this manuscript.
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Summary
Keywords
tranexamic acid, posterior lumbar interbody fusion, mode of administration, timing and dose of administration, research progress
Citation
Dong W, Tang Y, Zhou Y, Li J, Wu C, Liu Y, Yan Y, Peng Z and Zhao J (2025) Application and research progress of tranexamic acid in the perioperative period of posterior lumbar interbody fusion. Front. Med. 12:1612281. doi: 10.3389/fmed.2025.1612281
Received
15 April 2025
Accepted
21 July 2025
Published
08 August 2025
Volume
12 - 2025
Edited by
Xin Li, National Cancer Institute at Frederick (NIH), United States
Reviewed by
Germano Emílio Conceição-Souza, Hospital Alemão Oswaldo Cruz, Brazil
Lu Zhang, Affiliated Hospital of Jining Medical University, China
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Copyright
© 2025 Dong, Tang, Zhou, Li, Wu, Liu, Yan, Peng and Zhao.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jun Zhao 13678428203@163.comZhenggang Peng spinemedicine@163.com
†These authors have contributed equally to this work and share first authorship
‡These authors have contributed equally to this work and share last authorship
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