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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 -
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 -
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 -
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 -
Frontiers of Neurology and Neuroscience 2016Symptomatic cerebral atherosclerosis including intracranial atherosclerosis (ICAS) is associated with a high risk of recurrent stroke. Antithrombotic agents are the... (Review)
Review
Symptomatic cerebral atherosclerosis including intracranial atherosclerosis (ICAS) is associated with a high risk of recurrent stroke. Antithrombotic agents are the mainstay of therapy in these patients. Several studies have found anticoagulation (warfarin) to increase the risk of bleeding events and have an efficacy no better than that of aspirin. Therefore, anticoagulants are not widely used unless patients develop recurrent ischemic symptoms despite receiving antiplatelet therapy. Because ICAS progression is not uncommon and the risk of stroke recurrence is high when aspirin monotherapy is used, dual antiplatelet agents may be needed at least in the early disease stage. The Trial of Cilostazol in Symptomatic Intracranial Stenosis (TOSS) found that aspirin plus cilostazol was significantly better than aspirin monotherapy in preventing progression (6.7 vs. 28.8%, p = 0.008). The TOSS II trial that compared aspirin plus cilostazol with aspirin plus clopidogrel found no significant difference in the progression rate (9.3% vs. 15.5%, p = 0.092). However, the overall changes in stenosis were more favorable (i.e., less progression and more regression) in the cilostazol group (p = 0.049). TOSS studies have limitations in that the end points were changes in magnetic resonance angiography results rather than clinical outcomes. Based on the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial results, and the fair outcome found in patients enrolled in the SAMMPRIS (Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis) trial, aspirin plus clopidogrel has been recommended in the early stage of symptomatic ICAS. However, the combination of aspirin and clopidogrel did not show superiority over aspirin monotherapy in ICAS patients in a recent CHANCE substudy. Considering that ICAS is the major pathology leading to stroke worldwide, further studies are needed to identify the best medication strategy in ICAS patients. Until then, physicians may choose appropriate antiplatelet agents after careful consideration of the characteristics of both the patients (i.e., degree of stenosis, stroke mechanism, risk of stroke, and risk of bleeding) and the antiplatelet agent (e.g., side effect, cost).
Topics: Antifibrinolytic Agents; Fibrinolytic Agents; Humans; Intracranial Arteriosclerosis
PubMed: 27960183
DOI: 10.1159/000448310 -
Anesthesiology Mar 2018Fibrinolysis is a physiologic component of hemostasis that functions to limit clot formation. However, after trauma or surgery, excessive fibrinolysis may contribute to... (Review)
Review
Fibrinolysis is a physiologic component of hemostasis that functions to limit clot formation. However, after trauma or surgery, excessive fibrinolysis may contribute to coagulopathy, bleeding, and inflammatory responses. Antifibrinolytic agents are increasingly used to reduce bleeding, allogeneic blood administration, and adverse clinical outcomes. Tranexamic acid is the agent most extensively studied and used in most countries. This review will explore the role of fibrinolysis as a pathologic mechanism, review the different pharmacologic agents used to inhibit fibrinolysis, and focus on the role of tranexamic acid as a therapeutic agent to reduce bleeding in patients after surgery and trauma.
Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Loss, Surgical; Fibrinolysis; Humans; Perioperative Care; Tranexamic Acid
PubMed: 29200009
DOI: 10.1097/ALN.0000000000001997 -
Annals of Emergency Medicine Jun 2021Epistaxis is a common emergency department (ED) presentation and, if simple first aid measures fail, can lead to a need for anterior nasal packing. Tranexamic acid is an... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVE
Epistaxis is a common emergency department (ED) presentation and, if simple first aid measures fail, can lead to a need for anterior nasal packing. Tranexamic acid is an agent that contributes to blood clot stability. The aim of this study is to investigate the effectiveness of topical intranasal tranexamic acid in adult patients presenting to the ED with persistent epistaxis, and whether it reduces the need for anterior nasal packing.
METHODS
From May 5, 2017, to March 31, 2019, a double-blind, placebo-controlled, multicenter, 1:1, randomized controlled trial was conducted across 26 EDs in the United Kingdom. Participants with spontaneous epistaxis, persisting after simple first aid and the application of a topical vasoconstrictor, were randomly allocated to receive topical tranexamic acid or placebo. The primary outcome was the need for anterior nasal packing of any kind during the index ED attendance. Secondary outcome measures included hospital admission, need for blood transfusion, recurrent epistaxis, and any thrombotic events requiring any hospital reattendance within 1 week.
RESULTS
The study sample consisted of 496 participants with spontaneous epistaxis, persisting after simple first aid and application of a topical vasoconstrictor. In total, 211 participants (42.5%) received anterior nasal packing during the index ED attendance, including 111 of 254 (43.7%) in the tranexamic acid group versus 100 of 242 (41.3%) in the placebo group. The difference was not statistically significant (odds ratio 1.107; 95% confidence interval 0.769 to 1.594; P=.59). Furthermore, there were no statistically significant differences between tranexamic acid and placebo for any of the secondary outcome measures.
CONCLUSION
In patients presenting to an ED with atraumatic epistaxis that is uncontrolled with simple first aid measures, topical tranexamic acid applied in the bleeding nostril on a cotton wool dental roll is no more effective than placebo at controlling bleeding and reducing the need for anterior nasal packing.
Topics: Administration, Intranasal; Aged; Antifibrinolytic Agents; Bandages; Double-Blind Method; Emergency Service, Hospital; Epistaxis; Female; Humans; Male; Tranexamic Acid; United Kingdom
PubMed: 33612282
DOI: 10.1016/j.annemergmed.2020.12.013