Tranexamic acid and trauma coagulopathy: where are we now?

Hanley, Ciara; Callum, Jeannie; Jerath, Angela

doi:10.1016/j.bja.2020.09.014

Cited by 10 publications

(5 citation statements)

References 46 publications

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“…Rapid degradation of TA9 prevented the destruction of normal veins and tissues after TA9 diffusion, and endowed the hydrogel with excellent biodegradability and biocompatibility, since the metabolites TA and 1-nonanol had no apparent toxicity on cells and did not affect the coagulation systems of the animals. Previous studies have shown that TA could improve platelet function and inhibit plasmin-induced platelet activation to promote the stability of existing clots rather than increase the risk of thrombosis [25]. Besides, plasminogen and plasmin played a vital role in the process of connecting fibrinolysis and the inflammatory system.…”

Section: Discussionmentioning

confidence: 99%

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RETRACTED: A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy

et al. 2022

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Venous malformation (VM), which causes severe damage to patients’ appearance and organ function, is one of the most common vascular malformations. At present, many drugs in clinical treatment cause various adverse reactions. Herein, we synthesized cationic amphiphilic gelators (TA6, TA8, and TA9) by introducing saturated carbon chains of different lengths to tranexamic acid (TA), which could self-assemble into low-molecular-weight gels (LMWGs) as drug delivery carriers by hydrogen bonds, van der Waals forces, and hydrophobic interactions. The rheological properties, gelation driving force and drug release profiles of TA6, TA8, and TA9 hydrogels were characterized, and the results indicated that the hydrogels prepared in this study possessed the typical characteristics of a gel and could release drugs slowly. More importantly, the TA9 gelator showed significant pharmacological activity, in that it served as both an active drug compound and a drug carrier. The in vitro experiments demonstrated that TA9 induced HUVECs death and hemolysis by destroying cell membranes in a dose-dependent manner, and caused cell death and hemolysis at a concentration of 0.09 µM/mL. Meanwhile, we found TA9 could interact not only with fibrinogen, but also with other endogenous molecules in the blood. After the administration of TA9 hydrogel for 15 days, macroscopic imaging and histological evaluation in mice and rabbits displayed obvious thrombi, inflammatory reactions, and venous embolization, indicating that the mechanism of the TA9 hydrogel in treating VM was involved in two processes. Firstly, the TA9 hydrogel relied on its mechanical strength to physically block veins and continuously release TA9, in situ, for targeted therapy. Then, TA9 destroyed endothelial cells and damaged venous walls critically, causing thrombi. Most excitingly, TA9 was hydrolyzed to TA by enzymes that inhibited the degradation of thrombi by plasmin to prolong the embolization time and to promote venous fibrosis. Compared with other clinically available sclerosants, the degradation of TA9 also empowered a better biocompatibility and biodegradability for the TA9 hydrogel. In conclusion, we synthesized a potentially safe and effective derivative of TA and developed a low-molecular-weight gel as a self-delivery system for TA in treating VM.

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Section: Discussionmentioning

confidence: 99%

“…TA, also known as trans-4-aminomethyl-cyclohexane-carboxylic acid, is commonly used clinically to stanch bleeding during surgery, as a tyrosinase inhibitor [25]. As a hydrophilic lysine analog, TA has amino and carboxyl groups that can be modified.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy

et al. 2022

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“…19 It is now generally accepted that TXA must be given within 3 hours to have a positive effect on trauma patients. 20–23…”

Section: Discussionmentioning

confidence: 99%

“…19 It is now generally accepted that TXA must be given within 3 hours to have a positive effect on trauma patients. [20][21][22][23] The study by Cornelius et al 10 found that TXA is associated with higher mortality, however, that study had some serious limitations. The matching between the TXA group and control group was not identical as the TXA group had higher ISS, which affected the results of the study.…”

Section: Meta-analysismentioning

confidence: 99%

Pre-hospital administration of tranexamic acid in trauma patients: A systematic review and meta-analysis

Alhenaki

Ali

Kadir

et al. 2021

Trauma

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Background The Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-2 (CRASH-2) trial proved that tranexamic acid (TXA) is a time-dependent drug, having a better outcome if given within 1-hour of injury. In order to test this theory, studies have been conducted to examine the effect of TXA in the pre-hospital setting. We conducted a systematic search and meta-analysis to evaluate the role of TXA administration in the civilian pre-hospital setting on patient outcomes. Methods Embase, Medline, CINAHL and Cochrane were searched for randomized control trials (RCTs), retrospective, and prospective studies that examined the effect of TXA on patients in the pre-hospital setting versus a control group. Outcome measures were overall mortality rate and thromboembolic events. Two authors extracted the data independently. To appraise the included studies, we used the NIH quality assessment tool for cohort and cross-sectional studies. Results are presented as Risk Ratio (RR), a random-effect model was implemented, and the I2 test was used to assess heterogeneity. Results The search identified 1886 papers, but only five retrospective studies met the inclusion/exclusion criteria and were selected for further analysis. A meta-analysis confirmed that TXA reduced the overall mortality rate (pooled risk ratio of 0.74 (95% CI 0.45, 1.25)) and thromboembolic events (risk ratio of 0.71 (95% CI 0.35, 1.44)). Conclusion The pooled effects for both outcome measures favour the administration of TXA in the pre-hospital setting, although none of the findings reported a significant effect. Our study highlights the need for additional high-quality evidence to validate the significance of these findings. Level of evidence Level III, therapeutic study.

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“…In addition, TXA also exhibits secondary effects by inhibiting plasmin. TXA improves platelet function and inhibits plasmininduced platelet activation which facilitates clot stabilization [20].…”

Section: Mechanism Of Action and Pharmacokinetics Of Txamentioning

confidence: 99%

Tranexamic Acid in Trauma Management: A Review of Evidence

Kim

2023

J Acute Care Surg

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Hemorrhage is the leading cause of death in trauma patients and trauma induced coagulopathy (TIC) is a major contributor to bleeding mortality. TIC has a diverse pathophysiology triggered by injury and hypoperfusion, including platelet dysfunction, endotheliopathy, fibrinogen or thrombin abnormalities, and dysregulated fibrinolysis. Early fluid resuscitation, appropriate blood transfusion, and definitive control of bleeding are essential components of initial management for TIC. Additionally, tranexamic acid (TXA), an antifibrinolytic agent, has emerged as a potential adjunctive therapy following the 2010 landmark trial that demonstrated the benefit of early administration of TXA in reducing trauma patient mortality (CRASH-2). This review provides an analysis of the current literature on the use of TXA in trauma patients. It critically evaluates the evidence on the effect of TXA on TIC and other clinical outcomes, emphasizing the time-sensitive nature of TXA administration and the variation of its effect depending on the severity and location of injury. It also discusses the optimal dosage, timing, and safety of TXA, as well as the challenges and limitations of existing studies. Furthermore, it highlights the importance of individualized treatment approaches based on the fibrinolysis status of TIC and the value of goal-directed therapy guided by viscoelastic hemostatic assays for the appropriate use of TXA.

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Tranexamic acid and trauma coagulopathy: where are we now?

Cited by 10 publications

References 46 publications

RETRACTED: A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy

RETRACTED: A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy

Pre-hospital administration of tranexamic acid in trauma patients: A systematic review and meta-analysis

Tranexamic Acid in Trauma Management: A Review of Evidence

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