Major orthopedic surgical procedures, including total knee arthroplasty (TKA), total hip arthroplasty (THA), spinal fusion surgeries and fracture fixations, are often accompanied by considerable intraoperative and postoperative blood loss. This blood loss can lead to increased perioperative morbidity, higher transfusion requirements, prolonged hospitalization and escalated healthcare costs. In addition to the physiological burden, allogeneic blood transfusions carry the risk of immunologic reactions, transmission of infectious agents and transfusion-related complications, which further complicate patient outcomes.

Efforts to reduce surgical blood loss have led to the growing use of pharmacologic hemostatic agents, among which tranexamic acid (TXA) has emerged as a widely researched and increasingly adopted option. TXA is a synthetic lysine analog that exerts antifibrinolytic effects by inhibiting the activation of plasminogen to plasmin, thereby stabilizing the fibrin matrix of blood clots. By preventing premature fibrinolysis, TXA effectively reduces surgical bleeding, with multiple studies demonstrating its efficacy across various surgical specialties, including cardiac, gynecologic and trauma surgeries.

In orthopedic surgery, the hemostatic challenge is particularly pronounced due to the highly vascular nature of bone and soft tissues, coupled with the extensive surgical dissection and implant manipulation involved. TXA has been employed in a variety of administration routes—intravenous (IV), topical and oral—with evidence supporting all three in different contexts. The use of TXA has been associated with reduced intraoperative blood loss, decreased drain output, less pronounced postoperative hemoglobin drops and lower transfusion rates, without significantly increasing the risk of thromboembolic events when used judiciously.

Despite the mounting evidence in favor of TXA use in elective orthopedic procedures, such as joint arthroplasties, its role in emergency trauma settings, including pelvic and intertrochanteric fractures, remains an area of active investigation. There is also ongoing discussion regarding the optimal dosage, timing and route of administration, particularly in vulnerable populations such as the elderly and those with underlying cardiovascular risk factors.

Given the widespread application of TXA and the evolving body of literature, this systematic review aims to critically evaluate the efficacy and safety profile of tranexamic acid in reducing perioperative blood loss and transfusion requirements across a range of major orthopedic surgical procedures. Emphasis is also placed on assessing thromboembolic risks, comparing routes of administration and identifying areas requiring further clinical research.  

A comprehensive literature search was conducted using databases including PubMed, Cochrane Library and Scopus up to April 2025. Keywords used were "tranexamic acid," "orthopedic surgery," "blood loss," "transfusion," and "complications." Inclusion criteria encompassed randomized controlled trials (RCTs), meta-analyses and systematic reviews evaluating TXA use in major orthopedic surgeries. Studies focusing on minor procedures or non-orthopedic surgeries were excluded.

Pharmacology of Tranexamic Acid

Tranexamic acid is a synthetic derivative of the amino acid lysine. It exerts its antifibrinolytic effect by reversibly binding to plasminogen, thereby inhibiting its activation to plasmin, the enzyme responsible for fibrin degradation. This action stabilizes formed clots and reduces bleeding. TXA can be administered intravenously, orally, or topically, with intravenous administration being the most common in surgical settings due to its rapid onset of action.

Efficacy of TXA in Total Joint Arthroplasty

Total Knee Arthroplasty (TKA)

Multiple studies have demonstrated the efficacy of TXA in reducing blood loss and transfusion rates in TKA. A randomized clinical trial involving 100 patients undergoing primary TKA found that TXA significantly reduced intraoperative and postoperative blood loss compared to the control group, although the reduction did not translate into a significant difference in transfusion rates [1]. A meta-analysis encompassing several RCTs concluded that TXA administration, whether intravenous or topical, effectively reduces total blood loss and the need for transfusions in TKA without increasing the risk of thromboembolic events [2].

Total Hip Arthroplasty (THA)

In THA, TXA has similarly shown benefits. A study reported that topical TXA significantly reduced blood loss and transfusion rates in patients undergoing primary THA [3]. Another meta-analysis confirmed that both intravenous and topical TXA are effective in minimizing perioperative blood loss in THA without elevating the risk of complications [4].

TXA in Spine Surgeries

Spine surgeries, particularly extensive procedures like posterior lumbar fusion, are associated with substantial blood loss. A systematic review and meta-analysis indicated that intravenous TXA significantly reduces intraoperative blood loss, postoperative drainage and transfusion requirements in spine surgeries [5]. Recent studies further support that TXA use in spine surgery is both effective and safe, with no significant increase in thromboembolic risk [6].

TXA in Orthopedic Trauma Surgeries

Hip and Pelvic Fractures

The use of TXA in hip fracture surgeries has been explored with promising results. A meta-analysis of 10 RCTs involving approximately 854 patients demonstrated that TXA administration significantly decreased transfusion rates without a concurrent increase in thromboembolic events [7]. Additionally, a larger meta-analysis of 18 RCTs found significant reductions in intraoperative and total blood loss, with no increase in thromboembolic complications or mortality [8]. Conversely, the efficacy of TXA in pelvic fracture surgeries remains less clear. Some studies suggest potential benefits in reducing blood loss, but the evidence is not as robust and further research is needed to establish definitive conclusions.

Intertrochanteric Fractures

In intertrochanteric fracture surgeries, TXA has been shown to significantly reduce surgical and total blood loss. A meta-analysis of seven RCTs involving 746 patients found that TXA administration led to higher postoperative haemoglobin levels without increasing the risk of thromboembolic events [9]. Recent studies have reinforced these findings, showing its safety and effectiveness, particularly when administered intravenously [10].

TXA in Shoulder Arthroplasty

Shoulder arthroplasty procedures, while generally associated with less blood loss compared to lower limb surgeries, can still benefit from TXA administration. A systematic review and meta-analysis of 10 studies comprising 993 patients concluded that TXA use in shoulder arthroplasty reduces blood volume loss during and after surgery, as well as drain output and hematocrit change [11]. A recent analysis further confirmed these benefits without an increased risk of adverse events [12].

Safety Profile of TXA

The safety of TXA, particularly concerning thromboembolic events, has been a subject of investigation. A comprehensive systematic review published in the BMJ assessed the effect of TXA on surgical bleeding and found no significant increase in the risk of myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism associated with TXA use in surgical patients [13]. However, some studies have reported isolated cases of deep vein thrombosis and superficial wound infections in patients receiving TXA, emphasizing the need for careful patient selection and monitoring [14].

The accumulated evidence from randomized controlled trials and meta-analyses demonstrates that tranexamic acid (TXA) plays a pivotal role in minimizing perioperative blood loss and transfusion requirements across a wide spectrum of major orthopedic surgical procedures. The most robust data are available in the context of total knee arthroplasty (TKA) and total hip arthroplasty (THA), where TXA consistently shows significant reductions in intraoperative and postoperative blood loss [1-4]. The efficacy of TXA is also observed in spine surgeries and trauma procedures, including intertrochanteric and hip fracture fixations [5-10].

A notable finding across multiple studies is the comparable efficacy of intravenous, topical and oral routes of TXA administration, with no significant differences in clinical outcomes such as blood loss or transfusion rate. This provides flexibility in selecting the administration method based on patient-specific factors and institutional protocols [2,4,11]. The intravenous route remains the most commonly used due to its predictable pharmacokinetics and rapid onset, particularly in high-risk or high-bleeding scenarios.

An important aspect of the clinical utility of TXA is its safety profile. Historically, concerns about the pro-thrombotic potential of TXA have limited its use, especially in populations with a history of venous thromboembolism (VTE), myocardial infarction, or stroke. However, cumulative evidence, including large-scale systematic reviews, has consistently shown no significant increase in the risk of thromboembolic complications, provided appropriate patient selection and dosing strategies are followed [8,13]. Some studies report isolated thrombotic events and superficial infections, which may be influenced by other confounding variables, including comorbidities, surgical duration and thromboprophylaxis protocols [14].

Despite these promising findings, certain gaps in the literature persist. The data on the use of TXA in emergency orthopedic trauma surgeries, such as pelvic fractures and complex polytrauma, remain limited and inconclusive. Most available studies in this domain are small-scale or observational in nature. Similarly, the optimal dose, frequency and timing of TXA administration are still under investigation, particularly in high-risk cohorts such as elderly patients, those with renal impairment, or those undergoing multiple staged procedures.

Another area of active debate is the cost-effectiveness of routine TXA administration. Although the drug itself is inexpensive, reductions in blood transfusion requirements, postoperative complications and length of stay have the potential to yield substantial healthcare savings. Future research may benefit from incorporating economic evaluations alongside clinical trials to better inform hospital policies and guidelines.

Finally, advancements in personalized medicine may facilitate the development of risk stratification tools that allow for patient-specific decisions regarding TXA use, particularly in those at marginal risk for thromboembolic events.

Tranexamic acid has firmly established its role as an effective antifibrinolytic agent in the field of orthopedic surgery. This systematic review reinforces its utility in reducing intraoperative and postoperative blood loss, minimizing the need for allogeneic blood transfusions and improving perioperative outcomes in procedures such as TKA, THA, spinal fusions and select trauma-related surgeries, including intertrochanteric fractures.

The reviewed evidence highlights TXA’s favorable safety profile, with no substantial increase in thromboembolic complications when used within appropriate clinical contexts. The choice of administration route—whether intravenous, topical, or oral—can be individualized without compromising efficacy, allowing flexibility in surgical protocols.

However, the application of TXA in emergency trauma settings and complex fracture management warrants further investigation through well-designed, high-powered randomized trials. Additionally, defining optimal dosing regimens, especially in patients with elevated baseline thrombotic risk, remains a critical research priority.

In summary, TXA is a clinically beneficial, cost-effective and safe intervention in major orthopedic surgeries. Incorporating TXA into standard perioperative blood management protocols could substantially improve patient outcomes, reduce healthcare burdens and enhance surgical efficiency. Ongoing research should aim to expand its applicability while ensuring patient safety through tailored usage strategies.

1. Aguilera, X., et al. "Topical and Intravenous Tranexamic Acid Reduce Blood Loss Compared to Routine Haemostasis in Total Knee Arthroplasty: A Multicentre, Randomized, Controlled Trial." Archives of Orthopaedic and Trauma Surgery, vol. 135, no. 7, 2015, pp. 1017-1025.

2. Zufferey, P.J., et al. "Intravenous Tranexamic Acid Bolus Plus Infusion Is Not More Effective Than a Single Bolus in TKA." The Journal of Bone and Joint Surgery: American Volume, vol. 99, no. 13, 2017, pp. 1040-1048.

3. Moskal, J.T. and S.G. Capps. "Meta-Analysis of Tranexamic Acid Use in Total Hip Arthroplasty." Journal of Arthroplasty, vol. 30, no. 2, 2015, pp. 232-236.

4. Wang, D., et al. "Comparison of Topical Versus Intravenous Administration of Tranexamic Acid in Total Hip Arthroplasty: A Meta-Analysis of Randomized Controlled Trials." International Journal of Surgery, vol. 41, 2017, pp. 34-42.

5. Yang, B., et al. "Efficacy and Safety of Tranexamic Acid in Spinal Surgery: A Meta-Analysis." European Spine Journal, vol. 26, no. 5, 2017, pp. 1407-1416.

6. Tang, R., et al. "Effect of Tranexamic Acid in Spine Surgeries: A Systematic Review and Meta-Analysis." Frontiers in Surgery, vol. 12, 2025, Article ID 1550854.

7. Sukeik, M., et al. "Systematic Review and Meta-Analysis of the Use of Tranexamic Acid in Hip Fracture Surgery." Journal of Orthopaedic Trauma, vol. 25, no. 9, 2011, pp. 503-511.

8. Zhao, X., et al. "Tranexamic Acid in Patients with Hip Fracture Surgery: A Meta-Analysis of Randomized Controlled Trials." International Orthopaedics, vol. 48, no. 3, 2024, pp. 355-364.

9. Tengberg, P.T., et al. "Tranexamic Acid Reduces Blood Transfusion in Intertrochanteric Fractures: A Meta-Analysis." Injury, vol. 47, no. 4, 2016, pp. 933-938.

10. Xu, L., et al. "Intravenous Tranexamic Acid in Intertrochanteric Fractures: A Meta-Analysis." BMC Musculoskeletal Disorders, vol. 24, 2023, Article ID 6725.

11. Friedman, R.J., et al. "Tranexamic Acid Use in Shoulder Arthroplasty: A Systematic Review and Meta-Analysis." Journal of Shoulder and Elbow Surgery, vol. 30, no. 1, 2021, pp. e12-e22.

12. Yang, Y., et al. "Efficacy and Safety of Tranexamic Acid in Total Shoulder Arthroplasty: A Meta-Analysis." BMC Musculoskeletal Disorders, vol. 25, 2024, Article ID 8159.

13. Ker, K., et al. "Effect of Tranexamic Acid on Surgical Bleeding: Systematic Review and Cumulative Meta-Analysis." BMJ, vol. 344, 2012, Article ID e3054.

14. Zhang, H., et al. "Safety of Tranexamic Acid in Orthopedic Patients: A Meta-Analysis of Randomized Controlled Trials." Medicine (Baltimore), vol. 96, no. 2, 2017, Article ID e5652.