Tranexamic acid is toxic on human chondrocytes, in vitro

Jacob, Benjamin; Kloss, Nadja; Böhle, Sabrina; Kirschberg, Julia; Zippelius, Timo; Heinecke, Markus; Matziolis, Georg; Röhner, Eric

doi:10.1016/j.jor.2019.12.008

Cited by 15 publications

(13 citation statements)

References 17 publications

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“…TXA is a synthetic derivate of the essential amino acid lysine. It inhibits the conversion from plasminogen to plasmin by blocking the lysine binding site on plasmin and therefore limiting the fibrinolytic effects of plasmin [8]. Systemic intravenous treatment with TXA is widely regarded as safe.…”

Section: Introductionmentioning

confidence: 99%

“…This is especially important in partial joint surface replacements of the knee and hip joints, which preserve large parts of native hyaline cartilage and joint-forming bone. However, only a limited number of studies has examined the effects of TXA on chondrocytes, providing inconsistent results regarding toxicity and recommendations for clinical use [3,8,[10][11][12][13][14]. Interestingly, to date, there are hardly any studies investigating the effects of TXA on mesenchymal stromal cells (MSCs), which can be found in a variety of tissues forming and surrounding the human hip and knee joint [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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Impact of Tranexamic Acid on Chondrocytes and Osteogenically Differentiated Human Mesenchymal Stromal Cells (hMSCs) In Vitro

Wagenbrenner¹,

Heinz²,

Horas³

et al. 2020

JCM

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The topical application of tranexamic acid (TXA) helps to prevent post-operative blood loss in total joint replacements. Despite these findings, the effects on articular and periarticular tissues remain unclear. Therefore, this in vitro study examined the effects of varying exposure times and concentrations of TXA on proliferation rates, gene expression and differentiation capacity of chondrocytes and human mesenchymal stromal cells (hMSCs), which underwent osteogenic differentiation. Chondrocytes and hMSCs were isolated and multiplied in monolayer cell cultures. Osteogenic differentiation of hMSCs was induced for 21 days using a differentiation medium containing specific growth factors. Cell proliferation was analyzed using ATP assays. Effects of TXA on cell morphology were examined via light microscopy and histological staining, while expression levels of tissue-specific genes were measured using semiquantitative RT-PCR. After treatment with 50 mg/mL of TXA, a decrease in cell proliferation rates was observed. Furthermore, treatment with concentrations of 20 mg/mL of TXA for at least 48 h led to a visible detachment of chondrocytes. TXA treatment with 50 mg/mL for at least 24 h led to a decrease in the expression of specific marker genes in chondrocytes and osteogenically differentiated hMSCs. No significant effects were observed for concentrations beyond 20 mg/mL of TXA combined with exposure times of less than 24 h. This might therefore represent a safe limit for topical application in vivo. Further research regarding in vivo conditions and effects on hMSC functionality are necessary to fully determine the effects of TXA on articular and periarticular tissues.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of Tranexamic Acid on Chondrocytes and Osteogenically Differentiated Human Mesenchymal Stromal Cells (hMSCs) In Vitro

Wagenbrenner¹,

Heinz²,

Horas³

et al. 2020

JCM

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“…Further, it has been suggested recently that TXA can be cytotoxic to human chondrocytes. 34,35 Although this recent finding would limit the feasibility of using topical TXA around articular cartilage, it is noteworthy that the dose used in this study as well as the duration of exposure is considerably lower than in the above studies. Further, TXA-induced chondrocyte toxicity is not uncontested in the literature, with shorter duration of exposure at typical treatment doses revealing no chondrocyte toxicity.…”

Section: Limitationsmentioning

confidence: 88%

Topical tranexamic acid in hip fractures: a randomized, placebo-controlled double-blinded study

Costain

Elder

Fraser

et al. 2021

cjs

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Background: Tranexamic acid (TXA) has been shown to reduce perioperative blood loss in elective orthopedic surgery. The safety of intravenous TXA in nonelective hip fracture surgery is uncertain. The purpose of this study was to evaluate the efficacy and safety of topical TXA in hip fracture surgery. Methods: Adult patients presenting to a community hospital with a hip fracture requiring surgery were randomly assigned to receive topical TXA or placebo. Hemoglobin and troponin I levels were measured preoperatively and on postoperative days 1, 2 and 3. All postoperative blood transfusions were recorded. Complications, including acute coronary syndrome (ACS), venous thromboembolism (VTE), cerebrovascular accidents (CVA), surgical site infections (SSI) and 90-day mortality, were recorded. Results: Data were analyzed for 65 patients (31 in the TXA group, 34 in the control group). Hemogloblin level was significantly higher on postoperative days 1 and 2 in the TXA group than in the control group. The difference in hemoglobin level between the groups was not statistically significant by postoperative day 3. Significantly fewer units of packed red blood cells were transfused in the TXA group (2 units v. 8 units); however, 2 of the units in the control group were given intraoperatively, and when these were excluded the difference was not significant. The incidence of ACS, CVA, VTE, SSI, transfusion and all-cause mortality at 90 days did not differ significantly between the groups. Conclusion: Topical TXA reduces early postoperative blood loss after hip fracture surgery without increased patient risk. Trial registration: Clinicaltrials.gov, no. NCT02993341.

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“…This reflects the many years’ clinical practice and proven efficacy of intraarticular injection of the substances tested. However cytotoxicity of vancomycin, tranexamic acid and local anesthetics could be demonstrated by several studies and combination therapy would be very likely to increase local cytotoxic effects 31 – 33 .…”

Section: Discussionmentioning

confidence: 99%

The bactericidal effect of vancomycin is not altered by tranexamic acid, adrenalin, dexamethasone, or lidocaine in vitro

Schwerdt¹,

Röhner²,

Böhle³

et al. 2021

Sci Rep

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One of the most challenging complications of total knee arthroplasty (TKA) is periprosthetic joint infection (PJI). There is growing evidence of a good anti-infective effect of intrawound vancomycin powder in total joint arthroplasty. At the same time, various different locally applied substances have become popular in total joint arthroplasty. The objective of this study was therefore to investigate a possible inhibition of the bactericidal effect of vancomycin by tranexamic acid, adrenalin, lidocaine, or dexamethasone. The bactericidal effect of vancomycin was quantified using the established method of the agar diffusion test. The plates were incubated with Staphylococcus aureus or Staphylococcus epidermidis and four wells were stamped out. The wells were filled with vancomycin alone, the tested substance alone or a mixture of the two. The fourth well remained empty as a control. The plates were incubated overnight at 37 °C and the zone of inhibition in each field was measured on the next day. All tests were run three times for each pathogen and mean values and standard deviations of the measurements were calculated. Differences between the substances were tested using the t-test at a level of significance of 0.05. The bacterial growth was homogeneous on all plates. The baseline value for the zone of inhibition of vancomycin was on average 6.2 ± 0.4 mm for Staphylococcus aureus and 12 ± 0.3 mm for Staphylococcus epidermidis. In all other substances, no inhibition was detected around the well. The combination of vancomycin and each other substance did not show any different result compared to vancomycin alone. The bactericidal effect of vancomycin on staphylococci is not altered by tranexamic acid, adrenalin, dexamethasone, or lidocaine in vitro.

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Tranexamic acid is toxic on human chondrocytes, in vitro

Cited by 15 publications

References 17 publications

Impact of Tranexamic Acid on Chondrocytes and Osteogenically Differentiated Human Mesenchymal Stromal Cells (hMSCs) In Vitro

Impact of Tranexamic Acid on Chondrocytes and Osteogenically Differentiated Human Mesenchymal Stromal Cells (hMSCs) In Vitro

Topical tranexamic acid in hip fractures: a randomized, placebo-controlled double-blinded study

The bactericidal effect of vancomycin is not altered by tranexamic acid, adrenalin, dexamethasone, or lidocaine in vitro

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