-
The Journal of Dermatological Treatment Jun 2022Melasma is a common chronic refractory disorder of pigmentation affecting people with darker skin types. Overall prevalence varies between 8.8% and 40%, depending on the... (Review)
Review
Melasma is a common chronic refractory disorder of pigmentation affecting people with darker skin types. Overall prevalence varies between 8.8% and 40%, depending on the ethnicity of the population and the geographical area. Therapeutic management of melasma is challenging, with high recurrence rates which significant impacts on the quality of life. No single treatment is universally efficacious. Systemic treatments with tranexamic acid and polypodium leucotmatous had promising results, although the former was related to systemic side effects. Microneedling and peeling were also efficacious, although their superiority to topical hydroquinone, the gold standard in melasma treatment, remains to be established. Similarly, laser and light devices have been beneficial. However, recurrence rates remain high in all treatment groups. Combination therapies, either in double or triple combinations yielded the best results when compared to single terapies. Treatment choice should be made after Wood's lamp examination, as well as dermatoscopic evaluation, in order to select the best treatment option, targeted at each melasma subtype.
Topics: Administration, Cutaneous; Humans; Melanosis; Quality of Life; Tranexamic Acid; Treatment Outcome
PubMed: 33849384
DOI: 10.1080/09546634.2021.1914313 -
Brazilian Journal of Anesthesiology... 2022Tranexamic acid (TXA) significantly reduces blood loss in a wide range of surgical procedures and improves survival rates in obstetric and trauma patients with severe... (Review)
Review
Tranexamic acid (TXA) significantly reduces blood loss in a wide range of surgical procedures and improves survival rates in obstetric and trauma patients with severe bleeding. Although it mainly acts as a fibrinolysis inhibitor, it also has an anti-inflammatory effect, and may help attenuate the systemic inflammatory response syndrome found in some cardiac surgery patients. However, the administration of high doses of TXA has been associated with seizures and other adverse effects that increase the cost of care, and the administration of TXA to reduce perioperative bleeding needs to be standardized. Tranexamic acid is generally well tolerated, and most adverse reactions are considered mild or moderate. Severe events are rare in clinical trials, and literature reviews have shown tranexamic acid to be safe in several different surgical procedures. However, after many years of experience with TXA in various fields, such as orthopedic surgery, clinicians are now querying whether the dosage, route and interval of administration currently used and the methods used to control and analyze the antifibrinolytic mechanism of TXA are really optimal. These issues need to be evaluated and reviewed using the latest evidence to improve the safety and effectiveness of TXA in treating intracranial hemorrhage and bleeding in procedures such as liver transplantation, and cardiac, trauma and obstetric surgery.
Topics: Pregnancy; Female; Humans; Tranexamic Acid; Antifibrinolytic Agents; Hemorrhage; Orthopedic Procedures; Blood Loss, Surgical
PubMed: 34626756
DOI: 10.1016/j.bjane.2021.08.022 -
Anaesthesiology Intensive Therapy 2015Blood loss and subsequent transfusions are associated with major morbidity and mortality. The use of antifibrinolytics can reduce blood loss in cardiac surgery, trauma,... (Review)
Review
Blood loss and subsequent transfusions are associated with major morbidity and mortality. The use of antifibrinolytics can reduce blood loss in cardiac surgery, trauma, orthopedic surgery, liver surgery and solid organ transplantation, obstetrics and gynecology, neurosurgery and non-surgical diseases. The evidence of their efficacy has been mounting for years. Tranexamic acid (TXA), a synthetic lysine-analogue antifibrinolytic, was first patented in 1957 and its use has been increasing in contrast to aprotinin, a serine protease inhibitor antifibrinolytic. This review aims to help acute care physicians navigate through the clinical evidence available for TXA therapy, develop appropriate dose regimens whilst minimizing harm, as well as understand its broadening scope of applications. Many questions remain unanswered regarding other clinical effects of TXA such as anti-inflammatory response to cardiopulmonary bypass, the risk of thromboembolic events, adverse neurological effects such as seizures, and its morbidity and mortality, all of which necessitate further clinical trials on its usage and safety in various clinical settings.
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; General Surgery; Humans; Tranexamic Acid
PubMed: 25797505
DOI: 10.5603/AIT.a2015.0011 -
Lancet (London, England) Jun 2020Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial.
BACKGROUND
Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.
METHODS
We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.
FINDINGS
Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82-1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).
INTERPRETATION
We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial.
FUNDING
UK National Institute for Health Research Health Technology Assessment Programme.
Topics: Acute Disease; Adult; Aged; Antifibrinolytic Agents; Case-Control Studies; Double-Blind Method; Female; Gastrointestinal Hemorrhage; Humans; Injections, Intravenous; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Outcome Assessment, Health Care; Placebos; Predictive Value of Tests; Pulmonary Embolism; Stroke; Thromboembolism; Tranexamic Acid; Venous Thrombosis
PubMed: 32563378
DOI: 10.1016/S0140-6736(20)30848-5 -
Acta Dermato-venereologica Jul 2017Tranexamic acid is a novel treatment option for melasma; however, there is no consensus on its use. This systematic review searched major databases for relevant... (Meta-Analysis)
Meta-Analysis Review
Tranexamic acid is a novel treatment option for melasma; however, there is no consensus on its use. This systematic review searched major databases for relevant publications to March 2016. Eleven studies with 667 participants were included. Pooled data from tranexamic acid-only observational studies with pre- and post-treatment Melasma Area and Severity Index (MASI) showed a decrease of 1.60 in MASI (95% confidence interval (CI), 1.20-2.00; p<0.001) after treat-ment with tranexamic acid. The addition of tranexamic acid to routine treatment modalities resulted in a further decrease in MASI of 0.94 (95% CI 0.10-1.79; p = 0.03). Side-effects were minor, with a few cases reporting hypo-menorrhoea, mild abdominal discomfort, and transient skin irritation. These results support the efficacy and safety of tranexamic acid, either alone or as an adjuvant to routine treatment modalities for melasma.
Topics: Chi-Square Distribution; Dermatologic Agents; Humans; Keratinocytes; Melanins; Melanocytes; Melanosis; Severity of Illness Index; Skin Pigmentation; Tranexamic Acid; Treatment Outcome
PubMed: 28374042
DOI: 10.2340/00015555-2668 -
JAMA Jul 2022Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of High- vs Low-Dose Tranexamic Acid Infusion on Need for Red Blood Cell Transfusion and Adverse Events in Patients Undergoing Cardiac Surgery: The OPTIMAL Randomized Clinical Trial.
IMPORTANCE
Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery.
OBJECTIVE
To compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass.
DESIGN, SETTING, AND PARTICIPANTS
Multicenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to April 21, 2021; final follow-up was on May 21, 2021.
INTERVENTIONS
Participants received either a high-dose tranexamic acid regimen comprising a 30-mg/kg bolus, a 16-mg/kg/h maintenance dose, and a 2-mg/kg prime (n = 1525) or a low-dose regimen comprising a 10-mg/kg bolus, a 2-mg/kg/h maintenance dose, and a 1-mg/kg prime (n = 1506).
MAIN OUTCOMES AND MEASURES
The primary efficacy end point was the rate of allogeneic red blood cell transfusion after start of operation (superiority hypothesis), and the primary safety end point was a composite of the 30-day postoperative rate of mortality, seizure, kidney dysfunction (stage 2 or 3 Kidney Disease: Improving Global Outcomes [KDIGO] criteria), and thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis, and pulmonary embolism) (noninferiority hypothesis with a margin of 5%). There were 15 secondary end points, including the individual components of the primary safety end point.
RESULTS
Among 3079 patients who were randomized to treatment groups (mean age, 52.8 years; 38.1% women), 3031 (98.4%) completed the trial. Allogeneic red blood cell transfusion occurred in 333 of 1525 patients (21.8%) in the high-dose group and 391 of 1506 patients (26.0%) in the low-dose group (risk difference [RD], -4.1% [1-sided 97.55% CI, -∞ to -1.1%]; relative risk, 0.84 [1-sided 97.55% CI, -∞ to 0.96; P = .004]). The composite of postoperative seizure, thrombotic events, kidney dysfunction, and death occurred in 265 patients in the high-dose group (17.6%) and 249 patients in the low-dose group (16.8%) (RD, 0.8%; 1-sided 97.55% CI, -∞ to 3.9%; P = .003 for noninferiority). Fourteen of the 15 prespecified secondary end points were not significantly different between groups, including seizure, which occurred in 15 patients (1.0%) in the high-dose group and 6 patients (0.4%) in the low-dose group (RD, 0.6%; 95% CI, -0.0% to 1.2%; P = .05).
CONCLUSIONS AND RELEVANCE
Among patients who underwent cardiac surgery with cardiopulmonary bypass, high-dose compared with low-dose tranexamic acid infusion resulted in a modest statistically significant reduction in the proportion of patients who received allogeneic red blood cell transfusion and met criteria for noninferiority with respect to a composite primary safety end point consisting of 30-day mortality, seizure, kidney dysfunction, and thrombotic events.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03782350.
Topics: Adult; Antifibrinolytic Agents; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Dose-Response Relationship, Drug; Erythrocyte Transfusion; Female; Hemorrhage; Humans; Male; Middle Aged; Seizures; Thrombosis; Tranexamic Acid
PubMed: 35881121
DOI: 10.1001/jama.2022.10725 -
The New England Journal of Medicine Aug 2018The use of tranexamic acid reduces mortality due to postpartum hemorrhage. We investigated whether the prophylactic administration of tranexamic acid in addition to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The use of tranexamic acid reduces mortality due to postpartum hemorrhage. We investigated whether the prophylactic administration of tranexamic acid in addition to prophylactic oxytocin in women with vaginal delivery would decrease the incidence of postpartum hemorrhage.
METHODS
In a multicenter, double-blind, randomized, controlled trial, we randomly assigned women in labor who had a planned vaginal delivery of a singleton live fetus at 35 or more weeks of gestation to receive 1 g of tranexamic acid or placebo, administered intravenously, in addition to prophylactic oxytocin after delivery. The primary outcome was postpartum hemorrhage, defined as blood loss of at least 500 ml, measured with a collector bag.
RESULTS
Of the 4079 women who underwent randomization, 3891 had a vaginal delivery. The primary outcome occurred in 156 of 1921 women (8.1%) in the tranexamic acid group and in 188 of 1918 (9.8%) in the placebo group (relative risk, 0.83; 95% confidence interval [CI], 0.68 to 1.01; P=0.07). Women in the tranexamic acid group had a lower rate of provider-assessed clinically significant postpartum hemorrhage than those in the placebo group (7.8% vs. 10.4%; relative risk, 0.74; 95% CI, 0.61 to 0.91; P=0.004; P=0.04 after adjustment for multiple comparisons post hoc) and also received additional uterotonic agents less often (7.2% vs. 9.7%; relative risk, 0.75; 95% CI, 0.61 to 0.92; P=0.006; adjusted P=0.04). Other secondary outcomes did not differ significantly between the two groups. The incidence of thromboembolic events in the 3 months after delivery did not differ significantly between the tranexamic acid group and the placebo group (0.1% and 0.2%, respectively; relative risk, 0.25; 95% CI, 0.03 to 2.24).
CONCLUSIONS
Among women with vaginal delivery who received prophylactic oxytocin, the use of tranexamic acid did not result in a rate of postpartum hemorrhage of at least 500 ml that was significantly lower than the rate with placebo. (Funded by the French Ministry of Health; TRAAP ClinicalTrials.gov number, NCT02302456 .).
Topics: Adult; Antifibrinolytic Agents; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Intention to Treat Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Risk Factors; Thromboembolism; Tranexamic Acid
PubMed: 30134136
DOI: 10.1056/NEJMoa1800942 -
Health Technology Assessment... Apr 2021Tranexamic acid safely reduces mortality in traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury and can cause brain herniation... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tranexamic acid safely reduces mortality in traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury and can cause brain herniation and death. We assessed the effects of tranexamic acid in traumatic brain injury patients.
OBJECTIVE
To assess the effects of tranexamic acid on death, disability and vascular occlusive events in traumatic brain injury patients. We also assessed cost-effectiveness.
DESIGN
Randomised trial and economic evaluation. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers and those assessing outcomes were masked to allocation. All analyses were by intention to treat. We assessed the cost-effectiveness of tranexamic acid versus no treatment from a UK NHS perspective using the trial results and a Markov model.
SETTING
175 hospitals in 29 countries.
PARTICIPANTS
Adults with traumatic brain injury within 3 hours of injury with a Glasgow Coma Scale score of ≤ 12 or any intracranial bleeding on computerised tomography scan, and no major extracranial bleeding, were eligible.
INTERVENTION
Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo.
MAIN OUTCOME MEASURES
Head injury death in hospital within 28 days of injury in patients treated within 3 hours of injury. Secondary outcomes were early head injury deaths, all-cause and cause-specific mortality, disability, vascular occlusive events, seizures, complications and adverse events.
RESULTS
Among patients treated within 3 hours of injury ( = 9127), the risk of head injury death was 18.5% in the tranexamic acid group versus 19.8% in the placebo group (855/4613 vs. 892/4514; risk ratio 0.94, 95% confidence interval 0.86 to 1.02). In a prespecified analysis excluding patients with a Glasgow Coma Scale score of 3 or bilateral unreactive pupils at baseline, the results were 12.5% in the tranexamic acid group versus 14.0% in the placebo group (485/3880 vs. 525/3757; risk ratio 0.89, 95% confidence interval 0.80 to 1.00). There was a reduction in the risk of head injury death with tranexamic acid in those with mild to moderate head injury (166/2846 vs. 207/2769; risk ratio 0.78, 95% confidence interval 0.64 to 0.95), but in those with severe head injury (689/1739 vs. 685/1710; risk ratio 0.99, 95% confidence interval 0.91 to 1.07) there was no apparent reduction (-value for heterogeneity = 0.030). Early treatment was more effective in mild and moderate head injury ( = 0.005), but there was no obvious impact of time to treatment in cases of severe head injury ( = 0.73). The risk of disability, vascular occlusive events and seizures was similar in both groups. Tranexamic acid is highly cost-effective for mild and moderate traumatic brain injury (base case of £4288 per quality-adjusted life-year gained).
CONCLUSION
Early tranexamic acid treatment reduces head injury deaths. Treatment is cost-effective for patients with mild or moderate traumatic brain injury, or those with both pupils reactive.
FUTURE WORK
Further trials should examine early tranexamic acid treatment in mild head injury. Research on alternative routes of administration is needed.
LIMITATIONS
Time to treatment may have been underestimated.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN15088122, ClinicalTrials.gov NCT01402882, EudraCT 2011-003669-14, Pan African Clinical Trial Registry PACTR20121000441277.
FUNDING
The project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 26. See the NIHR Journals Library website for further project information. In addition, funding was provided by JP Moulton Charitable Trust, Joint Global Health Trials (Medical Research Council, Department for International Development and the Wellcome Trust). This project was funded by the NIHR Global Health Trials programme.
Topics: Adult; Antifibrinolytic Agents; Brain Injuries, Traumatic; Cost-Benefit Analysis; Craniocerebral Trauma; Glasgow Coma Scale; Humans; Tranexamic Acid
PubMed: 33928903
DOI: 10.3310/hta25260 -
Military Medical Research Mar 2020Hemorrhage is the leading cause of preventable death in combat trauma and the secondary cause of death in civilian trauma. A significant number of deaths due to... (Review)
Review
Hemorrhage is the leading cause of preventable death in combat trauma and the secondary cause of death in civilian trauma. A significant number of deaths due to hemorrhage occur before and in the first hour after hospital arrival. A literature search was performed through PubMed, Scopus, and Institute of Scientific Information databases for English language articles using terms relating to hemostatic agents, prehospital, battlefield or combat dressings, and prehospital hemostatic resuscitation, followed by cross-reference searching. Abstracts were screened to determine relevance and whether appropriate further review of the original articles was warranted. Based on these findings, this paper provides a review of a variety of hemostatic agents ranging from clinically approved products for human use to newly developed concepts with great potential for use in prehospital settings. These hemostatic agents can be administered either systemically or locally to stop bleeding through different mechanisms of action. Comparisons of current hemostatic products and further directions for prehospital hemorrhage control are also discussed.
Topics: Blood Coagulation Factors; Blood Platelets; Emergency Medical Services; Hemorrhage; Hemostasis; Hemostatics; Humans; Plasma; Polymers; Resuscitation; Tranexamic Acid
PubMed: 32209132
DOI: 10.1186/s40779-020-00241-z -
Seminars in Perinatology Feb 2019Blood product transfusion capabilities are crucial for appropriate response to postpartum hemorrhage. Novel treatments are continually being sought to improve maternal... (Review)
Review
Blood product transfusion capabilities are crucial for appropriate response to postpartum hemorrhage. Novel treatments are continually being sought to improve maternal morbidity and mortality associated with massive hemorrhage.
Topics: Antifibrinolytic Agents; Blood Transfusion; Clinical Protocols; Delivery, Obstetric; Female; Humans; Postpartum Hemorrhage; Pregnancy; Tranexamic Acid
PubMed: 30527516
DOI: 10.1053/j.semperi.2018.11.008