Study the Anti-inflammatory Effect of Tranexamic Acid When Used in Anterior Cruciate Ligament Reconstruction.

Tranexaminc Acid : Single Dose vs Placebo to Modulate Postoperative Inflammation After ACL Reconstruction : A Prospective, Randomized, Double-blind Trial

Tranexamic acid (TXA) is widely used in orthopedic surgery to reduce perioperative blood loss, particularly in total hip and knee arthroplasty, due to its antifibrinolytic mechanism, low cost, broad availability, and established safety profile. Its use has recently expanded to minimally invasive procedures such as knee arthroscopy and ACL reconstruction, where postoperative hemarthrosis-rather than intraoperative bleeding-is a major cause of pain, swelling, reduced range of motion, delayed rehabilitation, and impaired early recovery.

Randomized trials and meta-analyses in arthroscopic ACL reconstruction show that TXA, administered intravenously, intra-articularly, or both, reduces postoperative hemarthrosis, joint swelling, drainage volume, and early pain, while improving early functional outcomes. These benefits are mainly short term, with no consistent long-term differences, and no increased risk of thromboembolic events. Evidence in arthroscopic meniscectomy is more limited but suggests modest improvements in early recovery, which may still be clinically meaningful given TXA's favorable risk-benefit profile.

Beyond its antifibrinolytic effects, TXA may influence inflammatory pathways by inhibiting plasmin, which is involved in complement activation and inflammatory modulation. However, existing data are conflicting, with reports of both anti- and pro-inflammatory effects depending on surgical context and dosing. Importantly, most arthroscopy studies focus on clinical outcomes rather than systemic inflammation. To date, no study has comprehensively evaluated perioperative inflammatory responses to TXA in arthroscopic knee surgery, making this low-trauma setting an ideal model to investigate its potential inflammatory effects.

Over the past decade, tranexamic acid (TXA) has been widely adopted in orthopedic surgery to reduce perioperative blood loss and transfusion requirements, particularly in total hip and knee arthroplasty. TXA is a synthetic lysine analogue that inhibits the activation of plasminogen to plasmin, thereby preventing fibrin degradation and limiting fibrinolysis. Due to its low cost, wide availability, and well-established safety profile when administered intravenously, TXA is now routinely used in many countries for procedures associated with a high risk of bleeding.

In recent years, interest has expanded beyond major joint replacement toward minimally invasive orthopedic procedures, such as knee arthroscopy and anterior cruciate ligament (ACL) reconstruction. Although these procedures are generally associated with limited intraoperative blood loss, postoperative hemarthrosis remains the most frequent complication of knee arthroscopy and accounts for a substantial proportion of postoperative morbidity. Hemarthrosis has been shown to induce transient histological changes in articular cartilage and synovial tissue and is associated with increased postoperative pain, joint swelling, reduced range of motion (ROM), delayed rehabilitation, and impaired early functional recovery.

Several randomized controlled trials have investigated the role of TXA in arthroscopic knee surgery. In arthroscopic ACL reconstruction, multiple studies and subsequent systematic reviews and meta-analyses have demonstrated that TXA administration-whether intravenous, intra-articular, or combined-reduces postoperative hemarthrosis, joint swelling, drainage volume, and early postoperative pain, while improving early functional outcomes such as ROM and knee scores. These benefits appear most pronounced during the first postoperative weeks, with no consistent differences observed at longer-term follow-up. Importantly, these studies have not demonstrated an increased incidence of thromboembolic events or major complications associated with TXA use.

In the setting of arthroscopic meniscectomy, data are more limited. A double-blind randomized controlled trial evaluating intravenous TXA in routine arthroscopic meniscectomy suggested modest improvements in early functional recovery, particularly during the immediate postoperative period, despite minimal expected blood loss. Editorial commentaries and systematic reviews have emphasized that, although the absolute benefit of TXA in low-risk arthroscopic procedures may be small, even modest reductions in hemarthrosis and early inflammation may be clinically relevant given the low cost and favorable safety profile of the drug.

Beyond its antifibrinolytic properties, increasing experimental and clinical evidence suggests that TXA may exert biological effects on inflammation and coagulation pathways. Plasmin is known to play a role not only in fibrinolysis but also in the activation of the complement system and modulation of inflammatory mediators. By inhibiting plasmin generation, TXA may influence postoperative inflammatory responses. However, the available evidence remains conflicting. While some studies suggest anti-inflammatory effects, others-particularly in major orthopedic procedures such as total knee arthroplasty-have reported paradoxical increases in circulating pro-inflammatory cytokines following TXA administration.

These discordant findings highlight the complexity of the interaction between coagulation, fibrinolysis, and inflammation, and suggest that the effects of TXA on inflammatory pathways may depend on surgical context, tissue trauma, and dosing strategy. Importantly, most existing studies in arthroscopic surgery have focused primarily on clinical outcomes such as hemarthrosis, pain, and function, with very limited assessment of systemic inflammatory markers.

To date, no study has comprehensively evaluated the perioperative inflammatory response to TXA in arthroscopic knee surgery using serial cytokine measurements and integrated inflammatory burden assessment. Arthroscopic procedures, characterized by limited surgical trauma and low baseline inflammatory activation, represent an ideal clinical model to investigate the potential anti-inflammatory-or pro-inflammatory-effects of TXA in a controlled and sensitive manner.

Inclusion Criteria

• Adults aged 18 years or older.
• Male or female patients scheduled for primary anterior cruciate ligament (ACL) reconstruction.
• Surgery performed under spinal anesthesia, combined with a postoperative adductor canal block for analgesia.
• American Society of Anesthesiologists (ASA) physical status I or II.
• Procedure performed by a single, standardized surgical team.
• Ability to provide written informed consent.

Exclusion Criteria

• Age under 18 years.
• Pregnancy or breastfeeding.
• Preoperative treatment with anticoagulant or antiplatelet therapy that cannot be safely discontinued.
• Known coagulation disorders or history of abnormal bleeding.
• Known hypersensitivity or allergy to tranexamic acid.
• History of seizure disorders or epilepsy.