Faculty of Medicine Norwegian University of Science and Technology Trondheim Norway.
Department of Circulation and Medical Imaging Norwegian University of Science and Technology Trondheim Norway.
BJS Open. 2019 Sep 26;3(6):840-851. doi: 10.1002/bjs5.50192. eCollection 2019 Dec.
Topical administration of tranexamic acid (TXA) reduces bleeding from surgical wounds similarly to intravenous use, but with negligible risk of adverse systemic events. Topical use is expanding, but is off-label. Surgeons lack guidelines regarding safe topical dosages and modes of administration. The effects of topical TXA on skin cells and wound healing are unknown. This study investigated whether topical TXA might be cytotoxic or affect wound re-epithelialization.
Human keratinocytes and fibroblast cell cultures and an human skin wound model were subjected to both short (limited) and long (chronic) exposure to various clinically relevant concentrations of TXA to mimic different modalities of topical administration. Cytotoxicity and effects on wound re-epithelialization were evaluated.
In cell culture, toxicity from chronic exposure was associated with increasing concentration and exposure time. Limited exposure to TXA did not cause significant cytotoxicity even at high concentrations. Re-epithelialization was completely absent in wounds chronically exposed to TXA concentrations of 25 mg/ml or above, and 50-100 mg/ml induced epidermolysis of normal epithelium, possibly by a non-toxic mechanism. Wound re-epithelialization was slightly delayed, but not impaired, by limited exposure to 100 mg/ml or chronic exposure to 6·25 mg/ml.
Although short exposure to even high concentrations of topical TXA seems well tolerated , prolonged exposure can be cytotoxic and may affect wound re-epithelialization. Surgeons should adjust the TXA concentration to the planned mode of topical administration in clinical practice.
局部应用氨甲环酸（TXA）可减少手术伤口出血，效果与静脉使用相似，但发生全身不良事件的风险可忽略不计。局部应用正在扩大，但属于超适应证用药。外科医生缺乏关于安全局部剂量和给药方式的指南。TXA 对皮肤细胞和伤口愈合的影响尚不清楚。本研究旨在调查局部 TXA 是否具有细胞毒性，或是否会影响伤口再上皮化。
对人角质形成细胞和成纤维细胞培养物及人皮肤伤口模型进行了短时间（有限）和长时间（慢性）暴露于不同浓度的 TXA，以模拟不同的局部给药方式。评估了细胞毒性和对伤口再上皮化的影响。
在细胞培养中，慢性暴露引起的毒性与浓度和暴露时间的增加有关。即使在高浓度下，有限暴露于 TXA 也不会导致明显的细胞毒性。慢性暴露于 25 mg/ml 或更高浓度的 TXA 会导致完全丧失伤口再上皮化，而 50-100 mg/ml 则会导致正常上皮的表皮松解，可能通过非毒性机制。100 mg/ml 的有限暴露或 6.25 mg/ml 的慢性暴露会略微延迟但不会损害伤口再上皮化。
尽管短时间暴露于高浓度的局部 TXA 似乎可耐受，但长时间暴露可能具有细胞毒性，并可能影响伤口再上皮化。外科医生应根据临床实践中计划的局部给药方式调整 TXA 浓度。
