Topical use of tranexamic acid: Are there concerns for cytotoxicity?

Table 1 Characteristics and outcomes of studies that considered tranexamic acid as a safe drug

Ref.	Tissue	Doses	Time of exposure	Outcome
Ambra et al[3], 2017	Animal samples (Yucatan minipigs)	1, 2, and 4 mg/mL	1, 3, and 6 h	No effect on cell viability
Marmotti et al[4], 2016	Human samples (cartilage and synovial tissues)	7 mg/mL in both cartilage and synovial tissues	2 wk for cartilage tissue and 48 h for synovial tissue	No effect on synoviocyte morphology
Degirmenci et al[1], 2019	Animal samples (rabbits)	Not mentioned	Not mentioned	Healing rate was improved after TXA administration and no detrimental effects were observed
Bolam et al[29], 2020	Human and animal samples	1, 2, 4, 20, 25, 50, and 100 mg/mL	10 min, 1 h, 2 h, 4 h, 24 h, and 48 h	No effect on cell viability and morphology when treated at doses lower than 20 mg/mL
Wang et al[33], 2021	Human samples (fibroblast cells)	12, 5, 25, 50, and 100 mg/mL	10 min, 6 h, 12 h, 24 h, and 48 h	No effect on fibroblast cells in a time- and dose-dependent way

TXA: Tranexamic acid.

Table 2 Characteristics and outcomes of studies that proved cytotoxic effects of tranexamic acid

Ref.	Tissue	Doses	Time of exposure	Outcome
Tuttle et al[22], 2015	Animal samples (bovine and murine)	25, 50, and 100 mg/mL in murine chondrocytes and 100 mg/mL in bovine chondrocytes	8, 24, and 48 h for both bovine and murine explants	Cell viability was notably decreased as TXA dose and incubation time were increased
Parker et al[28], 2018	Human samples (chondrocytes on 2D and 3D models)	5, 10, 20, and 40 mg/mL in 2D cultures and 10, 20, and 40 mg/mL in 3D cultures	3, 6 and 12 h for the 2D models and 3 h for the 3D models	Cell viability, cellular metabolic activity, and number of attached cells were considerably decreased in a dose-dependent way
Goderecci et al[26], 2019	Human samples (chondrocytes)	20, 50, 70, and 100 mg/mL	10 min, 24 h, and 48 h	Chondrocyte viability and cell cycle profile were affected in a dose- and time-dependent way
McLean et al[27], 2019	Human samples (tendon, synovial, and cartilage tissues)	0, 1, 50, and 100 mg/mL	1, 4, and 24 h	Cell viability and apoptosis rate were affected at higher doses

TXA: Tranexamic acid.