-
Drugs Mar 2012Tranexamic acid, a synthetic derivative of the amino acid lysine, is an antifibrinolytic agent that acts by binding to plasminogen and blocking the interaction of... (Review)
Review
Tranexamic acid, a synthetic derivative of the amino acid lysine, is an antifibrinolytic agent that acts by binding to plasminogen and blocking the interaction of plasmin(ogen) with fibrin, thereby preventing dissolution of the fibrin clot. Tranexamic acid (Transamin®) is indicated in Japan for use in certain conditions with abnormal bleeding or bleeding tendencies in which local or systemic hyperfibrinolysis is considered to be involved. This article reviews the efficacy and tolerability of tranexamic acid in conditions amenable to antifibrinolytic therapy and briefly overviews the pharmacological properties of the drug. In large, randomized controlled trials, tranexamic acid generally significantly reduced perioperative blood loss compared with placebo in a variety of surgical procedures, including cardiac surgery with or without cardiopulmonary bypass, total hip and knee replacement and prostatectomy. In many instances, tranexamic acid also reduced transfusion requirements associated with surgery. It also reduced blood loss in gynaecological bleeding disorders, such as heavy menstrual bleeding, postpartum haemorrhage and bleeding irregularities caused by contraceptive implants. Tranexamic acid significantly reduced all-cause mortality and death due to bleeding in trauma patients with significant bleeding, particularly when administered early after injury. It was also effective in traumatic hyphaema, gastrointestinal bleeding and hereditary angioneurotic oedema. While it reduces rebleeding in subarachnoid haemorrhage, it may increase ischaemic complications. Pharmacoeconomic analyses predicted that tranexamic acid use in surgery and trauma would be very cost effective and potentially life saving. In direct comparisons with other marketed agents, tranexamic acid was at least as effective as ε-aminocaproic acid and more effective than desmopressin in surgical procedures. It was more effective than desmopressin, etamsylate, flurbiprofen, mefenamic acid and norethisterone, but less effective than the levonorgestrel-releasing intra-uterine device in heavy menstrual bleeding and was as effective as prednisolone in traumatic hyphaema. Tranexamic acid was generally well tolerated. Most adverse events in clinical trials were of mild or moderate severity; severe or serious events were rare. Therefore, while high-quality published evidence is limited for some approved indications, tranexamic acid is an effective and well tolerated antifibrinolytic agent.
Topics: Antifibrinolytic Agents; Cost-Benefit Analysis; Fibrinolysis; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 22397329
DOI: 10.2165/11209070-000000000-00000 -
Transfusion May 2023Tranexamic acid (TXA) is widely used as an antifibrinolytic agent in hemorrhagic trauma patients. The beneficial effects of TXA exceed the suppression of blood loss and...
INTRODUCTION
Tranexamic acid (TXA) is widely used as an antifibrinolytic agent in hemorrhagic trauma patients. The beneficial effects of TXA exceed the suppression of blood loss and include the ability to decrease inflammation and edema. We found that TXA suppresses the release of mitochondrial DNA and enhances mitochondrial respiration. These results allude that TXA could operate through plasmin-independent mechanisms. To address this hypothesis, we compared the effects of TXA on lipopolysaccharide (LPS)-induced expression of proinflammatory cytokines in plasminogen (Plg) null and Plg heterozygous mice.
METHODS
Plg null and Plg heterozygous mice were injected with LPS and TXA or LPS only. Four hours later, mice were sacrificed and total RNA was prepared from livers and hearts. Real time quantitative polymerase chain reaction with specific primers was used to assess the effects of LPS and TXA on the expression of pro-inflammatory cytokines.
RESULTS
LPS enhanced the expression of Tnfα in the livers and hearts of recipient mice. The co-injection of TXA significantly decreased the effect of LPS both in Plg null and heterozygous mice. A similar trend was observed with LPS-induced Il1α expression in hearts and livers.
CONCLUSIONS
The effects of TXA on the endotoxin-stimulated expression of Tnfα and Il1α in mice do not depend on the inhibition of plasmin generation. These results indicate that TXA has other biologically important target(s) besides plasminogen/plasmin. Fully understanding the molecular mechanisms behind the extensive beneficial effects of TXA and future identification of its targets may lead to improvement in the use of TXA in trauma, cardiac, and orthopedic surgical patients.
Topics: Mice; Animals; Tranexamic Acid; Fibrinolysin; Fibrinolytic Agents; Endotoxins; Tumor Necrosis Factor-alpha; Lipopolysaccharides; Antifibrinolytic Agents; Plasminogen; Hemorrhage
PubMed: 37070378
DOI: 10.1111/trf.17353 -
Advanced Emergency Nursing Journal 2014Trauma-related deaths represent a leading cause of mortality among persons younger than 45 years. A significant percentage of these are secondary to hemorrhage. In... (Review)
Review
Trauma-related deaths represent a leading cause of mortality among persons younger than 45 years. A significant percentage of these are secondary to hemorrhage. In trauma, massive and rapid loss of blood creates an imbalance in hemostasis. Mainstays of resuscitation include surgical interventions, restoring intravascular volume, and pharmacologic interventions. Providers continue to search for improved pharmacologic options for achieving hemostasis. Tranexamic acid is an antifibrinolytic and inhibits fibrinolysis by blocking the lysine-binding sites on plasminogen. Tranexamic acid works to stabilize and inhibit the degradation of existing clots. Tranexamic acid has been prospectively proven to reduce mortality in trauma-related hemorrhage. Its use will likely expand into such areas as resuscitation and massive transfusion protocols and the prehospital setting. Therefore, it is critical for emergency medicine providers to be familiar with appropriate use of tranexamic acid in order to maximize efficacy and decrease the potential adverse events.
Topics: Antifibrinolytic Agents; Education, Continuing; Hemorrhage; Humans; Tranexamic Acid; Wounds and Injuries
PubMed: 24785665
DOI: 10.1097/TME.0000000000000018 -
Plastic and Reconstructive Surgery Feb 2018Minimizing blood loss during surgery is critical, and many modalities have been used to decrease unwanted surgical bleeding. Among many methods, use of pharmacologic... (Review)
Review
Minimizing blood loss during surgery is critical, and many modalities have been used to decrease unwanted surgical bleeding. Among many methods, use of pharmacologic agents such as antifibrinolytic drugs has been shown to significantly reduce blood loss and the rates of postoperative blood transfusion in many articles. Tranexamic acid is an antifibrinolytic agent that has been widely used in other surgical specialties, especially in cardiac, orthopedic, and trauma surgery. Despite its known benefits, the use of tranexamic acid in plastic surgery is extremely limited, primarily because most plastic surgery procedures do not involve the extent of blood loss that can lead to anemia and the need for blood transfusion, as is common in major orthopedic and cardiac surgery procedures. Nevertheless, there are significant benefits to be gained from the use of antifibrinolytic drugs in the full range of plastic surgery. In this article, the authors introduce the benefits, dosages, and technical considerations of using tranexamic acid in plastic surgery procedures.
Topics: Anemia; Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Cardiac Surgical Procedures; Humans; Orthognathic Surgical Procedures; Orthopedic Procedures; Plastic Surgery Procedures; Tranexamic Acid
PubMed: 28938364
DOI: 10.1097/PRS.0000000000003926 -
Obstetrics and Gynecology Clinics of... Dec 2015Long-acting reversible contraception (LARC) is the most effective form of reversible contraception. Although most women are satisfied with LARC methods, unscheduled... (Review)
Review
Long-acting reversible contraception (LARC) is the most effective form of reversible contraception. Although most women are satisfied with LARC methods, unscheduled bleeding and spotting are common reasons for method dissatisfaction and discontinuation. This systematic analysis of the current literature delineates treatment options for unscheduled bleeding related to LARC use. Although consistent results are lacking, all devices seem to have the best response to nonsteroidal antiinflammatory drugs for 5 to 7 days or the antifibrinolytic agent tranexamic acid. Additional studies are necessary to identify improved treatment interventions for unscheduled bleeding with LARC use.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Antifibrinolytic Agents; Contraception; Doxycycline; Female; Hormone Antagonists; Humans; Intrauterine Devices, Copper; Intrauterine Devices, Medicated; Levonorgestrel; Matrix Metalloproteinase Inhibitors; Mifepristone; Practice Guidelines as Topic; Time Factors; Tranexamic Acid; Uterine Hemorrhage
PubMed: 26598302
DOI: 10.1016/j.ogc.2015.07.004 -
The Cochrane Database of Systematic... Jun 2015Postpartum haemorrhage (PPH) is a common and potentially life-threatening complication of labour. Several options for preventing PPH are available, but further advances... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postpartum haemorrhage (PPH) is a common and potentially life-threatening complication of labour. Several options for preventing PPH are available, but further advances in this field are important, especially the identification of safe, easy to use and cost-effective regimens. Tranexamic acid (TA), which is an antifibrinolytic agent that is used widely to prevent and treat haemorrhage, merits evaluation to assess whether it meets these criteria.
OBJECTIVES
To determine, from the best available evidence, whether TA is effective and safe for preventing PPH in comparison to placebo or no treatment (with or without uterotonic co-treatment), or to uterotonic agents.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 January 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
All published, unpublished and ongoing randomised controlled trials (RCTs) evaluating the use of TA alone or in addition to uterotonics in the third stage of labour or during caesarean section (CS) to prevent PPH.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed for inclusion all the potential studies identified as a result of the search strategy. We entered the data into Review Manager software and checked for accuracy.
MAIN RESULTS
Twelve trials involving 3285 healthy women at low risk of excessive bleeding undergoing elective CS (nine trials, 2453 participants) or spontaneous birth (three trials, 832 participants) satisfied inclusion criteria and contributed data to the analysis. All participants received routine prophylactic uterotonics in accordance with the local guideline in addition to TA or placebo or no intervention. Overall, included studies had moderate risk of bias for random sequence generation, allocation concealment, blinding, selective reporting and low risk of bias for incomplete data. The quality of evidence was also as assessed using GRADE.Blood loss greater than 400 mL or 500 mL, and more than 1000 mL was less common in women who received TA versus placebo or no intervention (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.42 to 0.63, six trials, 1398 women; moderate quality evidence) and (RR 0.40, 95% CI 0.23 to 0.71, six trials, 2093 women; moderate quality evidence), respectively. TA was effective in decreasing the incidence of blood loss greater than 1000 mL in women who had undergone CS (RR 0.43, 95% CI 0.23, 0.78, four trials, 1534 women), but not vaginal birth (RR 0.28, 95% CI 0.06, 1.36, two trials 559 women). The effect of TA on blood loss greater than 500 mL or 400 mL was more pronounced in the group of women having vaginal birth than in women who had CS. Mean blood loss (from delivery until two hours postpartum) was lower in women who received TA versus placebo or no intervention (mean difference MD - 77.79 mL, 95% CI -97.95, -57.64, five trials, 1186 women) and this effect was similar following vaginal birth and CS.Additional medical interventions (moderate quality evidence) and blood transfusions were less frequent in women receiving TA versus placebo or no interventions. Mild side effects such as nausea, vomiting, dizziness were more common with the use of TA (moderate quality evidence). The effect of TA on maternal mortality, severe morbidity and thromboembolic events is uncertain (low quality evidence).
AUTHORS' CONCLUSIONS
TA (in addition to uterotonic medications) decreases postpartum blood loss and prevents PPH and blood transfusions following vaginal birth and CS in women at low risk of PPH based on studies of mixed quality. There is insufficient evidence to draw conclusions about serious side effects, but there is an increase in the incidence of minor side effects with the use of TA. Effects of TA on thromboembolic events and mortality as well as its use in high-risk women should be investigated further.
Topics: Antifibrinolytic Agents; Female; Humans; Injections, Intravenous; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 26079202
DOI: 10.1002/14651858.CD007872.pub3 -
Medicine May 2020Antifibrinolytic agents have been successfully used to reduce blood transfusion demand in patients undergoing elective knee arthroplasty. The purpose of this study was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antifibrinolytic agents have been successfully used to reduce blood transfusion demand in patients undergoing elective knee arthroplasty. The purpose of this study was to investigate different antifibrinolytic agents for patients undergoing total-knee arthroplasty (TKA).
METHODS
We searched the randomized controlled trials assessing the effect of antifibrinolytic agents on TKA in MEDLINE, PubMed, Embase, and the Cochrane Library. Participants are divided into antifibrinolytic agent group and control group under TKA. Double extraction technology is used and the quality of its methodology is evaluated before analysis. Outcomes analyzed included blood loss, number of blood transfusions, rates of blood transfusion, and deep vein thrombosis (DVT).
RESULTS
A total of 28 randomized controlled trials involving 1899 patients were included in this study. Compared with the control group, the antifibrinolytic agents group exhibited significantly reduced the amounts of total blood loss (weighted mean difference [WMD] with 95% confidence interval [CI]: -272.19, -338.25 to -206.4), postoperative blood loss (WMD with 95% CI: -102.83, -157.64 to -46.02), average units of blood transfusion (risk ratio with 95% CI: 0.7, 0.12 to 0.24), and average blood transfusion volumes (WMD with 95% CI: -1.34, -1.47 to -1,21). Antifibrinolytic agents significantly reduced the rate of blood transfusions and did not increase the occurrence risk of intraoperative blood loss and DVT. Several limitations should also be acknowledged such as the heterogeneity among the studies.
CONCLUSION
The application of antifibrinolytic agents can significantly reduce blood loss and blood transfusion requirements. Additionally, these agents did not increase the risk of DVT in patients undergoing TKAs.
Topics: Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Humans; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 32443349
DOI: 10.1097/MD.0000000000020214 -
Hamostaseologie Oct 2022In premenopausal women treatment with direct oral anticoagulants (DOACs) can be associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin...
In premenopausal women treatment with direct oral anticoagulants (DOACs) can be associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists. These findings come from retrospective or prospective single-center studies and post hoc analysis of regulatory studies in which HMB was not a predefined safety outcome. In most of these publications, there is a lack of information about the use of different contraceptive methods which can influence HMB. Another limitation is the various definitions of HMB, which makes comparison between studies regarding the incidences of HMB difficult.Therefore, prospective studies are urgently needed to investigate the severity and duration of unaffected menstrual bleeding under oral anticoagulation independently of oral contraceptives or intrauterine devices. An ongoing multicenter German registry is aiming to compare the incidence of unaffected HMB in consecutive women of reproductive age (18-50 years) treated with different DOACs because of venous thromboembolism.When HMB occurs during oral anticoagulation, management includes interruption or dose reduction of anticoagulation with the danger of recurrent venous thrombosis, switch to another oral anticoagulant, or additional use of the antifibrinolytic agent tranexamic acid with the potential risk of thrombosis. Concomitant use of either oral hormonal contraceptive therapy or hormone-releasing intrauterine systems can also reduce HMB.
Topics: Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Prospective Studies; Retrospective Studies; Menorrhagia; Antifibrinolytic Agents; Anticoagulants; Contraceptives, Oral
PubMed: 36323281
DOI: 10.1055/a-1891-8187 -
Foot & Ankle Specialist Aug 2022Tranexamic acid (TXA) has become a commonly used perioperative intervention in total joint arthroplasty, shoulder and knee arthroscopy, and spinal procedures in order to... (Review)
Review
Tranexamic acid (TXA) has become a commonly used perioperative intervention in total joint arthroplasty, shoulder and knee arthroscopy, and spinal procedures in order to minimize blood loss, hematoma formation, hemarthrosis, and wound healing complications. There is a potential role for TXA use in foot and ankle procedures, with limited studies suggesting a potential benefit in minimizing postoperative wound complications and blood loss without an increased risk of thromboembolic events. In light of the profound clinical and financial impact of TXA use in other orthopaedic subspecialties and the early successes in foot and ankle surgery, we aim to provide more information about TXA and its use in foot and ankle surgery. Therefore, the purpose of this review is to perform a comprehensive literature review on the topic of TXA use in foot and ankle procedures in order to describe the pertinent available literature on the use of TXA in orthopaedic surgery and its implications specifically in foot and ankle surgery. It is our aim to identify potential benefits and shortcomings in the available evidence on TXA use for foot and ankle surgery in hopes to (1) best inform foot and ankle surgeons where beneficial and safe and (2) inspire further research on this topic as it relates to clinical management for foot and ankle patients. .
Topics: Ankle; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Humans; Tranexamic Acid
PubMed: 33401927
DOI: 10.1177/1938640020983639 -
European Archives of... Feb 2013Post-tonsillectomy haemorrhage is a serious complication that can lead to death despite the fact that tonsillectomy is one of the commonest procedures performed in... (Meta-Analysis)
Meta-Analysis Review
Post-tonsillectomy haemorrhage is a serious complication that can lead to death despite the fact that tonsillectomy is one of the commonest procedures performed in otolaryngology. Post-operative haemorrhage can be reduced by a potent antifibrinolytic agent such as tranexamic acid (TXA). This systematic review aims to evaluate the role of TXA in tonsillectomy. Searches were performed on MEDLINE, EMBASE, Web of Science and the Cochrane Library. Study selection, data extraction and quality assessment were conducted independently by two reviewers. Mean difference (MD) in volume of blood loss was calculated with 95 % confidence interval (CI). Risk ratios (RR) with 95 % CI were computed using random effects for the risk of post-tonsillectomy haemorrhage. This review identified and included a total of seven studies. Two studies (n = 180) compared the effects of TXA on volume of blood loss. Meta-analysis of these studies showed a significant decrease in the mean blood loss of 32.72 ml (95 % CI -42.66 to -22.78, p < 0.00001). Five studies (n = 1,670) compared the number of patients with post-tonsillectomy haemorrhage between TXA and control groups. TXA does not reduce the number of patients with post-tonsillectomy haemorrhage significantly (RR = 0.51, 95 % CI 0.25 to 1.07, p = 0.08). TXA led to a significant reduction of tonsillectomy blood loss volume but had no impact on the rate of patients with post-tonsillectomy haemorrhage. This systematic review demonstrated that most studies were conducted before 1980; therefore, a new, large and well-designed randomised controlled trial is needed to investigate the risks and benefits of TXA.
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Humans; Postoperative Hemorrhage; Tonsillectomy; Tranexamic Acid
PubMed: 22996082
DOI: 10.1007/s00405-012-2184-3