Editorial Commentary: Tranexamic Acid: Okay, It Reduces the Bleeding, but Are We Sure Topical Use Is Not Harmful to the Cartilage?

Karaaslan, Fatih

doi:10.1016/j.arthro.2019.04.014

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…9,13,23,47,64,67 Four RCTs administered IV TXA in arthroscopic procedures; however, in 2 studies, Chiang et al 12 and Karaaslan et al 33 administered TXA via intra-articular injection during ACL reconstruction for the presumed benefit of delivering efficacious doses to a surgical site with a lower systemic plasma concentration than that in oral or IV form. 16,18,50 The study by Chiang et al has sparked critique by experts in arthroscopy, 22,32,42,60 who have highlighted the conflicting literature that exists in regard to the safety of topical TXA administration to the joint microenvironment in vivo. 4,53 Interestingly, the reduction in postoperative drainage output and hemarthrosis grade was actually less in the RCT by Chiang et al, in which TXA was administered via intra-articular injection, in comparison with the 3 studies administering IV TXA.…”

Section: Discussionmentioning

confidence: 99%

Tranexamic Acid in Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis

et al. 2021

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Background: Hemarthrosis after anterior cruciate ligament (ACL) reconstruction procedures can delay rehabilitation and have toxic effects on the cartilage and synovium. Tranexamic acid is widely used in adult reconstruction procedures; however, its use in ACL reconstruction is a novel topic of study. Purpose: To analyze the available literature on hemarthrosis, pain, functional outcomes, and complications after administration of tranexamic acid in ACL reconstruction procedures. Study Design: Meta-analysis. Methods: A literature search was performed to retrieve randomized controlled trials examining the use of tranexamic acid at the time of ACL reconstruction procedures. The studied outcomes included postoperative joint drain output, hemarthrosis grade, visual analog scale scores for pain, range of motion, Lysholm score, postoperative rates of deep venous thrombosis, and pulmonary embolism. Outcomes were pooled to perform a meta-analysis. Results: Five prospective randomized controlled trials met inclusion criteria for analysis. Four studies administered intravenous tranexamic acid in bolus or infusion form before ACL reconstruction, while 2 studies administered tranexamic acid via intra-articular injection. Specifically, tranexamic acid was administered intravenously (preoperative 15-mg/kg bolus 10 minutes before tourniquet inflation with or without 10 mg/kg/h for 3 hours postoperatively) or intra-articularly (10 mL [100 mg/mL] intraoperatively), and 1 study consisted of tranexamic acid administration in combined intravenous and intra-articular forms (15-mg/kg bolus 10 minutes before tourniquet inflation and intra-articular 3 g 10 minutes before tourniquet deflation). Tranexamic acid use in ACL reconstruction cases resulted in a mean reduction of 61.5 mL in postoperative drain output at 24 hours (95% CI, –95.51 to −27.46; P = .0004), lower hemarthrosis grade ( P < .00001), improved Lysholm scores, and reduction in visual analog scale scores for pain (−1.96 points; 95% CI, −2.19 to −1.73; P < .00001) extending to postoperative week 6. Range of motion was improved in the immediate postoperative period, and the need for joint aspiration within 2 weeks was reduced ( P < .001). There was no difference in venous thromboembolic event rate between the experimental and control groups. Conclusion: The use of intravenous tranexamic acid in ACL reconstruction surgery results in reduced joint drain output and hemarthrosis and improved pain scores and range of motion in the initial postoperative period without increased complications or thromboembolic events.

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Section: Discussionmentioning

confidence: 99%

Tranexamic Acid in Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis

et al. 2021

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“…Topical treatment was administered weekly via intra-articular injections (5 μL of 20 mg·mL -1 TXA or vehicle) into the operated knees, starting on the day of surgery. Even though there are some concerns regarding the toxicity of TXA with high local levels against chondrocytes, tenocytes, synoviocytes, and osteoblasts, 9,30 concentrations <20 mg·mL are expected to be safe. 9,47 Therefore, the systemic and topical doses of TXA were within the safe concentration range in this study.…”

Section: Methodsmentioning

confidence: 99%

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice

Xie,

Jiang,

Donat

et al. 2024

Am J Sports Med

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Background: Posttraumatic osteoarthritis (OA) is a common disorder associated with a high socioeconomic burden, particularly in young, physically active, and working patients. Tranexamic acid (TXA) is commonly used in orthopaedic trauma surgery as an antifibrinolytic agent to control excessive bleeding. Previous studies have reported that TXA modulates inflammation and bone cell function, both of which are dysregulated during posttraumatic OA disease progression. Purpose: To evaluate the therapeutic effects of systemic and topical TXA treatment on the progression of posttraumatic OA in the knee of mice. Study Design: Controlled laboratory study. Methods: OA was induced via anterior cruciate ligament (ACL) transection on the right knee of female mice. Mice were treated with TXA or vehicle intraperitoneally daily or intra-articularly weekly for 4 weeks, starting on the day of surgery. Articular cartilage degeneration, synovitis, bone erosion, and osteophyte formation were scored histologically. Micro−computed tomography evaluation was conducted to measure the subchondral bone microstructure and osteophyte volume. Cartilage thickness and bone remodeling were assessed histomorphometrically. Results: Both systemic and topical TXA treatment significantly reduced cartilage degeneration, synovitis, and bone erosion scores and increased the ratio of hyaline to calcified cartilage thickness in posttraumatic OA. Systemic TXA reversed ACL transection-induced subchondral bone loss and osteophyte formation, whereas topical treatment had no effect. Systemic TXA decreased the number and surface area of osteoclasts, whereas those of osteoblasts were not affected. No effect of topical TXA on osteoblast or osteoclast parameters was observed. Conclusion: Both systemic and topical TXA exerted protective effects on the progression of posttraumatic OA. Drug repurposing of TXA may, therefore, be useful for the prevention or treatment of posttraumatic OA, particularly after ACL surgery. Clinical Relevance: TXA might be beneficial in patients with posttraumatic OA of the knee.

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“…In a study by Chiang et al, intra-articular injection (100 mg/mL) of TXA in patients undergoing ACL reconstruction resulted in decreased pain and a lower grade of hemarthrosis in the early postoperative phase without side effects 6 . However, the safe dose of TXA that can be administered in the knee joint during ACL reconstruction remains unclear, with concerns over potential toxicity to articular cartilage and meniscus 10,[12][13][14] . Tuttle et al observed that 25 mg/mL of TXA had no impact on murine chondrocyte viability, whereas 100 mg/mL resulted in no viable bovine chondrocytes 15 .…”

mentioning

confidence: 99%

In Vivo Effect of Single Intra-Articular Injection of Tranexamic Acid on Articular Cartilage and Meniscus

Wang,

Li,

Lin

et al. 2023

Journal of Bone and Joint Surgery

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Background: Tranexamic acid (TXA) has been increasingly used in arthroscopic surgery to prevent hemarthrosis. Despite its effectiveness, safety concerns have been raised regarding its potential cytotoxicity to articular cartilage and meniscus following intra-articular injection. Methods: To evaluate the impact of TXA on cartilage and meniscus, a rat model of knee instability was utilized wherein anterior cruciate ligament (ACL) transection surgery was followed by a single intra-articular injection of TXA at varying concentrations (0, 20, 50, 100, and 150 mg/mL) in saline solution. Cell viability assessment of the cartilage and meniscus (n = 6 per group) was conducted at 24 hours, and gross observation and histological analysis of the medial tibial plateau and medial meniscus were conducted at 2, 4, and 8 weeks (n = 6 per group and time point). Results: The chondrocyte viability was significantly decreased in the 50, 100, and 150 mg/mL TXA groups compared with the specimens injected with saline solution only (saline group) (p = 0.001, p < 0.001, p < 0.001, respectively), as was meniscal cell viability (p = 0.042, p < 0.001, p < 0.001, respectively). At week 8, the saline and 20 and 50 mg/mL groups showed relatively normal appearances, whereas the 100 and 150 mg/mL groups exhibited increased and varying severity of cartilage and meniscal degeneration. In the 150 mg/mL group, the mean Osteoarthritis Research Society International score was significantly higher than that in the saline and 20 mg/mL groups (p = 0.010 and p = 0.007). Additionally, the mean meniscus score in the 150 mg/mL group was significantly higher than that in the saline, 20 mg/mL, and 50 mg/mL groups (p = 0.020, p = 0.021, p = 0.031, respectively). Conclusions: Our findings indicate that concentrations of TXA at or above 100 mg/mL can lead to decreased cell viability in both cartilage and meniscus, resulting in significant cartilage degeneration in rats with ACL transection. Furthermore, the use of 150 mg/mL of TXA led to significant meniscal degeneration. Clinical Relevance: It is prudent to avoid using concentrations of TXA at or above 100 mg/mL for intra-articular injection, as such concentrations may result in adverse effects on the cartilage and meniscus.

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Editorial Commentary: Tranexamic Acid: Okay, It Reduces the Bleeding, but Are We Sure Topical Use Is Not Harmful to the Cartilage?

Cited by 4 publications

References 20 publications

Tranexamic Acid in Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis

Tranexamic Acid in Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice

In Vivo Effect of Single Intra-Articular Injection of Tranexamic Acid on Articular Cartilage and Meniscus

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