Effects of Tranexamic Acid Cytotoxicity on In Vitro Chondrocytes
Use of topical tranexamic acid (TXA) in orthopedic surgery has been expanding over the past decade, with increasing evidence confirming reductions in perioperative blood loss and transfusion requirements, but there is minimal evidence regarding effects of TXA on native cartilage.
We conducted a study to understand the in vitro effects of TXA on bovine cartilage and murine chondrocytes and ultimately to expand the clinical application of topical TXA to include scenarios with retained native cartilage, such as hemiarthroplasty. Bovine cartilage explants were exposed to TXA at a concentration of 100 mg/mL, and glycosaminoglycan (GAG) release and cell viability were measured at 8, 24, and 48 hours. Monolayer murine chondrocytes were exposed to TXA 25, 50, and 100 mg/mL, and viability was measured at 8, 24, and 48 hours.
GAG released from bovine explants was significantly higher in the samples exposed to TXA 100 mg/mL at all time points. Cell viability was significantly decreased in the explants exposed to TXA 24 and 48 hours after initial incubation. Bovine chondrocyte viability was not affected by TXA 25 mg/mL. Murine chondrocyte viability was similar between the TXA 25 mg/mL and control samples at all time points. The TXA 50 mg/mL sample dropped from 66.51% viability at 8 hours to 6.81% viability at 24 hours and complete cell death by 48 hours. The TXA 100 mg/mL samples had no observable viable cells at 8, 24, and 48 hours.
Our data indicated that TXA 100 mg/mL damaged and was cytotoxic to bovine explanted cartilage and was cytotoxic to murine chondrocytes. Murine and bovine chondrocyte viability were not affected by TXA 25 mg/mL.
Although its findings were highly reproducible, the present study had several limitations, including its in vitro nature and its use of a bovine and murine model rather than a human cell and tissue platform. It may be prudent to expose chondrocytes to TXA for a shorter time to try to mimic what theoretically occurs in vivo. In vivo studies may be a reasonable direction for experimentation. Clarifying the mechanism of cell death is of experimental interest as well. As the first of its kind, the present study provides an important initial database for exploration.
This study is the first to show that TXA has a cytotoxic effect on chondrocytes and that it damages cartilage at clinically used concentrations. Although more studies are needed to verify a safe concentration of TXA for topical use with human cartilage, our data indicate that TXA 25 mg/mL may be an effective yet safe dose for intra-articular use in native joints.
