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The New England Journal of Medicine Jul 2023Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and suspected trauma-induced coagulopathy who are being treated in advanced trauma systems is uncertain.
METHODS
We randomly assigned adults with major trauma who were at risk for trauma-induced coagulopathy to receive tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. The primary outcome was survival with a favorable functional outcome at 6 months after injury, as assessed with the use of the Glasgow Outcome Scale-Extended (GOS-E). Levels on the GOS-E range from 1 (death) to 8 ("upper good recovery" [no injury-related problems]). We defined survival with a favorable functional outcome as a GOS-E level of 5 ("lower moderate disability") or higher. Secondary outcomes included death from any cause within 28 days and within 6 months after injury.
RESULTS
A total of 1310 patients were recruited by 15 emergency medical services in Australia, New Zealand, and Germany. Of these patients, 661 were assigned to receive tranexamic acid, and 646 were assigned to receive placebo; the trial-group assignment was unknown for 3 patients. Survival with a favorable functional outcome at 6 months occurred in 307 of 572 patients (53.7%) in the tranexamic acid group and in 299 of 559 (53.5%) in the placebo group (risk ratio, 1.00; 95% confidence interval [CI], 0.90 to 1.12; P = 0.95). At 28 days after injury, 113 of 653 patients (17.3%) in the tranexamic acid group and 139 of 637 (21.8%) in the placebo group had died (risk ratio, 0.79; 95% CI, 0.63 to 0.99). By 6 months, 123 of 648 patients (19.0%) in the tranexamic acid group and 144 of 629 (22.9%) in the placebo group had died (risk ratio, 0.83; 95% CI, 0.67 to 1.03). The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups.
CONCLUSIONS
Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo. (Funded by the Australian National Health and Medical Research Council and others; PATCH-Trauma ClinicalTrials.gov number, NCT02187120.).
Topics: Adult; Humans; Antifibrinolytic Agents; Australia; Emergency Medical Services; Tranexamic Acid; Vascular Diseases; Wounds and Injuries; Blood Coagulation Disorders
PubMed: 37314244
DOI: 10.1056/NEJMoa2215457 -
Transfusion Aug 2022Tranexamic acid (TXA) is a popular antifibrinolytic drug widely used in hemorrhagic trauma patients and cardiovascular, orthopedic, and gynecological surgical patients.... (Review)
Review
Tranexamic acid (TXA) is a popular antifibrinolytic drug widely used in hemorrhagic trauma patients and cardiovascular, orthopedic, and gynecological surgical patients. TXA binds plasminogen and prevents its maturation to the fibrinolytic enzyme plasmin. A number of studies have demonstrated the broad life-saving effects of TXA in trauma, superior to those of other antifibrinolytic agents. Besides preventing fibrinolysis and blood loss, TXA has been reported to suppress posttraumatic inflammation and edema. Although the efficiency of TXA transcends simple inhibition of fibrinolysis, little is known about its mechanisms of action besides the suppression of plasmin maturation. Understanding the broader effects of TXA at the cell, organ, and organism levels are required to elucidate its potential mechanisms of action transcending antifibrinolytic activity. In this article, we provide a brief review of the current clinical use of TXA and then focus on the effects of TXA beyond antifibrinolytics such as its anti-inflammatory activity, protection of the endothelial and epithelial monolayers, stimulation of mitochondrial respiration, and suppression of melanogenesis.
Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Fibrinolysin; Fibrinolysis; Hemorrhage; Humans; Tranexamic Acid
PubMed: 35834488
DOI: 10.1111/trf.16976 -
Anaesthesia Jan 2022Globally, approximately 70 million people sustain traumatic brain injury each year and this can have significant physical, psychosocial and economic consequences for... (Review)
Review
Globally, approximately 70 million people sustain traumatic brain injury each year and this can have significant physical, psychosocial and economic consequences for patients, their families and society. The aim of this review is to provide clinicians with a summary of recent studies of direct relevance to the management of traumatic brain injury in order to promote best clinical practice. The use of tranexamic acid in the management of traumatic brain injury has been the focus of several studies, with one large randomised controlled trial suggesting a reduction in all-cause mortality within 24 h of injury. The use of therapeutic hypothermia does not improve neurological outcomes and maintenance of normothermia remains the optimal management strategy. For seizure management, levetiracetam appears to be as effective as phenytoin, but the optimal dose remains unclear. There has been a lack of clear outcome benefit for any individual osmotherapy agent, with no difference in mortality or neurological recovery. Early tracheostomy (< 7 days from injury) for patients with traumatic brain injury is associated with a reduction in the incidence of ventilator-associated pneumonia and duration of mechanical ventilation, critical care and hospital stay. Further research is needed in order to determine the optimal package of care and interventions. There is a need for research studies to focus on patient-centred outcome measures such as long-term neurological recovery and quality of life.
Topics: Anticonvulsants; Antifibrinolytic Agents; Brain Injuries, Traumatic; Disease Management; Evidence-Based Medicine; Humans; Randomized Controlled Trials as Topic
PubMed: 35001375
DOI: 10.1111/anae.15608 -
Neurotherapeutics : the Journal of the... Oct 2020Spontaneous intracerebral hemorrhage (ICH) results in high rates of morbidity and mortality, with intraventricular hemorrhage (IVH) being associated with even worse... (Review)
Review
Spontaneous intracerebral hemorrhage (ICH) results in high rates of morbidity and mortality, with intraventricular hemorrhage (IVH) being associated with even worse outcomes. Therapeutic interventions in acute ICH have continued to emerge with focus on arresting hemorrhage expansion, clot volume reduction of both intraventricular and parenchymal hematomas, and targeting perihematomal edema and inflammation. Large randomized controlled trials addressing the effectiveness of rapid blood pressure lowering, hemostatic therapy with platelet transfusion, and other clotting complexes and hematoma volume reduction using minimally invasive techniques have impacted clinical guidelines. We review the recent evolution in the management of acute spontaneous ICH, discussing which interventions have been shown to be safe and which may potentially improve outcomes.
Topics: Antifibrinolytic Agents; Antihypertensive Agents; Blood Pressure; Cerebral Hemorrhage; Hemostasis; Humans; Minimally Invasive Surgical Procedures
PubMed: 32720246
DOI: 10.1007/s13311-020-00902-w -
The New England Journal of Medicine Apr 2021Prophylactic administration of tranexamic acid has been associated with reduced postpartum blood loss after cesarean delivery in several small trials, but evidence of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Prophylactic administration of tranexamic acid has been associated with reduced postpartum blood loss after cesarean delivery in several small trials, but evidence of its benefit in this clinical context remains inconclusive.
METHODS
In a multicenter, double-blind, randomized, controlled trial, we assigned women undergoing cesarean delivery before or during labor at 34 or more gestational weeks to receive an intravenously administered prophylactic uterotonic agent and either tranexamic acid (1 g) or placebo. The primary outcome was postpartum hemorrhage, defined as a calculated estimated blood loss greater than 1000 ml or receipt of a red-cell transfusion within 2 days after delivery. Secondary outcomes included gravimetrically estimated blood loss, provider-assessed clinically significant postpartum hemorrhage, use of additional uterotonic agents, and postpartum blood transfusion.
RESULTS
Of the 4551 women who underwent randomization, 4431 underwent cesarean delivery, 4153 (93.7%) of whom had primary outcome data available. The primary outcome occurred in 556 of 2086 women (26.7%) in the tranexamic acid group and in 653 of 2067 (31.6%) in the placebo group (adjusted risk ratio, 0.84; 95% confidence interval [CI], 0.75 to 0.94; P = 0.003). There were no significant between-group differences in mean gravimetrically estimated blood loss or in the percentage of women with provider-assessed clinically significant postpartum hemorrhage, use of additional uterotonic agents, or postpartum blood transfusion. Thromboembolic events in the 3 months after delivery occurred in 0.4% of women (8 of 2049) who received tranexamic acid and in 0.1% of women (2 of 2056) who received placebo (adjusted risk ratio, 4.01; 95% CI, 0.85 to 18.92; P = 0.08).
CONCLUSIONS
Among women who underwent cesarean delivery and received prophylactic uterotonic agents, tranexamic acid treatment resulted in a significantly lower incidence of calculated estimated blood loss greater than 1000 ml or red-cell transfusion by day 2 than placebo, but it did not result in a lower incidence of hemorrhage-related secondary clinical outcomes. (Funded by the French Ministry of Health; TRAAP2 ClinicalTrials.gov number, NCT03431805.).
Topics: Administration, Intravenous; Adult; Antifibrinolytic Agents; Blood Transfusion; Cesarean Section; Double-Blind Method; Female; Humans; Postpartum Hemorrhage; Pregnancy; Pulmonary Embolism; Tranexamic Acid; Venous Thrombosis
PubMed: 33913639
DOI: 10.1056/NEJMoa2028788 -
The Journal of Trauma and Acute Care... Jan 2023There is strong evidence in adult literature that tranexamic acid (TXA) given within 3 hours from injury is associated with improved outcomes. The evidence for TXA use... (Randomized Controlled Trial)
Randomized Controlled Trial Observational Study
There is strong evidence in adult literature that tranexamic acid (TXA) given within 3 hours from injury is associated with improved outcomes. The evidence for TXA use in injured children is limited to retrospective studies and one prospective observational trial. Two studies in combat settings and one prospective civilian US study have found association with improved mortality. These studies indicate the need for a randomized controlled trial to evaluate the efficacy of TXA in injured children and to clarify appropriate timing, dose and patient selection. Additional research is also necessary to evaluate trauma-induced coagulopathy in children. Recent studies have identified three distinct fibrinolytic phenotypes following trauma (hyperfibrinolysis, physiologic fibrinolysis, and fibrinolytic shutdown), which can be identified with viscohemostatic assays. Whether viscohemostatic assays can appropriately identify children who may benefit or be harmed by TXA is also unknown.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Retrospective Studies; Prospective Studies; Hemorrhage; Blood Coagulation Disorders; Wounds and Injuries
PubMed: 36044459
DOI: 10.1097/TA.0000000000003775 -
International Journal of Dermatology May 2023Tranexamic acid is a plasmin inhibitor that is used off-label for the treatment of melasma. The use of tranexamic acid has expanded in the field of dermatology based on... (Review)
Review
Tranexamic acid is a plasmin inhibitor that is used off-label for the treatment of melasma. The use of tranexamic acid has expanded in the field of dermatology based on its anti-inflammatory and anti-melanin-producing properties, which include the treatment of rosacea, urticaria, and post-inflammatory hyperpigmentation. Tranexamic acid may have more uses in dermatology that require future studies. It should be used with caution during the COVID-19 pandemic given its procoagulant nature.
Topics: Humans; Tranexamic Acid; Dermatology; Pandemics; COVID-19; Antifibrinolytic Agents; Melanosis; Treatment Outcome
PubMed: 35323992
DOI: 10.1111/ijd.16160 -
The American Journal of Emergency... May 2021Tranexamic acid (TXA) is an antifibrinolytic agent which inhibits conversion of plasminogen to plasmin, a key step in kallikrein activation and bradykinin formation....
Tranexamic acid (TXA) is an antifibrinolytic agent which inhibits conversion of plasminogen to plasmin, a key step in kallikrein activation and bradykinin formation. Tranexamic acid is used in prophylactic management of hereditary angioedema; however, evidence for TXA in angiotensin converting enzyme (ACE) inhibitor-induced angioedema (ACEI-AE) is limited. We describe a patient who presented to the emergency department with ACEI-AE who was successfully treated with TXA. This case suggests that TXA may be a beneficial treatment modality in the management of ACEI-AE and warrants further investigation.
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antifibrinolytic Agents; Female; Humans; Lisinopril; Middle Aged; Tranexamic Acid
PubMed: 33164754
DOI: 10.1016/j.ajem.2020.10.029 -
The American Journal of Emergency... Jun 2022Over the last decade, tranexamic acid (TXA) has been incorporated into treatment algorithms for a multitude of emergent conditions and the evidence surrounding its role... (Review)
Review
INTRODUCTION
Over the last decade, tranexamic acid (TXA) has been incorporated into treatment algorithms for a multitude of emergent conditions and the evidence surrounding its role in emergency medicine continues to evolve.
OBJECTIVE
The objective of this literature review is to provide an evidence-based approach to the utilization of TXA in the emergency department.
DISCUSSION
The most robust trials suggest TXA may offer a modest improvement in mortality in patients at risk of significant bleeding from trauma, but is not beneficial in spontaneous intracranial hemorrhage or gastrointestinal bleeding. The role of TXA in other clinical scenarios is less clear and requires clinical judgment.
CONCLUSION
Tranexamic acid appears to be a reasonable adjunct for the emergency medicine clinician to consider in the management of many hemorrhagic conditions and angiotensin converting enzyme inhibitor-induced angioedema. Additional high-quality research in these areas is needed to further identity patients who may benefit most from TXA.
Topics: Angioedema; Antifibrinolytic Agents; Emergency Medicine; Gastrointestinal Hemorrhage; Humans; Tranexamic Acid
PubMed: 35364476
DOI: 10.1016/j.ajem.2022.03.027 -
Current Opinion in Anaesthesiology Dec 2022The particular fields within patient blood management (PBM) and patient safety reviewed here include novel insights into bleeding therapy, autologous cell salvage, and... (Review)
Review Meta-Analysis
PURPOSE OF REVIEW
The particular fields within patient blood management (PBM) and patient safety reviewed here include novel insights into bleeding therapy, autologous cell salvage, and perioperative anemia therapy.
RECENT FINDING
World Health Organization has published that implementation of PBM is important but has not yet been performed in all hospitals. Two antibodies that mimic the function of FVIII, Emicizumab, and Mim8 have been developed. Tranexamic acid (TXA) has been investigated further in patients with hip surgery and shows reduction of bleeding. Thrombocytopenia in patients undergoing cardiac surgery is a particular concern that has been investigated in another trial. The use of autologous cell salvage was updated in form of a review and meta-analysis. And last but not least, intravenous iron in preoperative anemia therapy can reduce the number of transfusions, but especially iron carboxymaltose can cause hypophosphatemia.
SUMMARY
PBM should be further implemented in more hospitals. Emicizumab and Mim8 are indicated in acquired hemophilia or hemophilia A with inhibitors. TXA was confirmed to reduce bleeding. Autologous cell salvage is state of the art to reduce transfusion requirements in major cardiac and noncardiac surgery. Serum phosphate concentrations should be monitored after administration of intravenous iron compounds.
Topics: Humans; Anemia; Antifibrinolytic Agents; Blood Loss, Surgical; Patient Safety; Tranexamic Acid
PubMed: 36194140
DOI: 10.1097/ACO.0000000000001196