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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 -
Orthopedics Jun 2004Aprotinin is a potent pharmacological agent that reduces bleeding. In current surgical practices, the rate of blood transfusions has decreased with the use of aprotinin.... (Review)
Review
Aprotinin is a potent pharmacological agent that reduces bleeding. In current surgical practices, the rate of blood transfusions has decreased with the use of aprotinin. Recently, studies using aprotinin have been conducted in orthopedic surgery. Several trials have been performed in patients undergoing total hip replacement and total knee replacement. Aprotinin moderately decreased blood loss in these patients. When aprotinin was used in patients with a high-risk of bleeding (ie, patients with cancer, sepsis, or undergoing reoperation), potent hemostatic activity occurred and the rate of blood transfusions significantly decreased. No increase in deep vein thrombosis and pulmonary embolism was observed. One adverse effect was the potential occurrence of an anaphylactoid reaction. Prophylactic administration of aprotinin should be considered in extensive spine surgery and in high-risk orthopedic operations. The decision to use aprotinin can be guided by a risk/benefit analysis.
Topics: Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Clinical Trials as Topic; Humans; Orthopedic Procedures
PubMed: 15239556
DOI: 10.3928/0147-7447-20040602-09 -
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 -
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 -
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 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 -
The Cochrane Database of Systematic... Nov 2016Haemoptysis is a common pathology around the world, occurring with more frequency in low-income countries. It has different etiologies, many of which have infectious... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Haemoptysis is a common pathology around the world, occurring with more frequency in low-income countries. It has different etiologies, many of which have infectious characteristics. Antifibrinolytic agents are commonly used to manage bleeding from different sources, but their usefulness in pulmonology is unclear.
OBJECTIVES
To evaluate the effectiveness and safety of antifibrinolytic agents in reducing the volume and duration of haemoptysis in adult and paediatric patients.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library, EMBASE and LILACS for publications that describe randomized controlled trials (RCTs) of antifibrinolytic therapy in patients presenting with haemoptysis. We also performed an independent search in MEDLINE for relevant trials not yet included in CENTRAL or DARE. Searches are up to date to the 19th September 2016. We conducted electronic and manual searches of relevant national and international journals. We reviewed the reference lists of included studies to locate relevant randomized controlled trials (RCTs). An additional search was carried out to find unpublished RCTs.
SELECTION CRITERIA
We included RCTs designed to evaluate the effectiveness and safety of antifibrinolytic agents in reducing haemoptysis in adult and paediatric patients of both genders presenting with haemoptysis of any etiology and severity. The intervention of interest was the administration of antifibrinolytic agents compared with placebo or no treatment.
DATA COLLECTION AND ANALYSIS
All reviewers independently assessed methodological quality and extracted data tables pre-designed for this review.
MAIN RESULTS
The electronic literature search identified 1 original study that met the eligibility criteria. One unpublished study was also identified through manual searches. Therefore two randomized controlled trials met the inclusion criteria: Tscheikuna 2002 (via electronic searches) and Ruiz 1994 (via manual searches). Tscheikuna 2002, a double-blind RCT performed in Thailand, evaluated the effectiveness of tranexamic acid (TXA, an antifibrinolytic agent) administered orally in 46 hospital in- and outpatients with haemoptysis of various etiologies. Ruiz 1994, a double-blind RCT performed in Peru, evaluated the effectiveness of intravenous TXA in 24 hospitalised patients presenting with haemoptysis secondary to tuberculosis.Pooled together, results demonstrated a significant reduction in bleeding time between patients receiving TXA and patients receiving placebo with a weighted mean difference (WMD) of -19.47 (95% CI -26.90 to -12.03 hours), but with high heterogeneity (I² = 52%). TXA did not affect remission of haemoptysis evaluated at seven days after the start of treatment. Adverse effects caused by the drug's mechanism of action were not reported. There was no significant difference in the incidence of mild side effects between active and placebo groups (OR 3.13, 95% CI 0.80 to 12.24).
AUTHORS' CONCLUSIONS
There is insufficient evidence to judge whether antifibrinolytics should be used to treat haemoptysis from any cause, though limited evidence suggests they may reduce the duration of bleeding.
Topics: Administration, Oral; Adult; Antifibrinolytic Agents; Hemoptysis; Humans; Injections, Intravenous; Peru; Randomized Controlled Trials as Topic; Thailand; Tranexamic Acid; Tuberculosis, Pulmonary
PubMed: 27806184
DOI: 10.1002/14651858.CD008711.pub3 -
Seminars in Thrombosis and Hemostasis Jul 2024Tranexamic acid (TXA) is an important antifibrinolytic agent, which inhibits plasminogen activation and fibrinolysis. Several controlled randomized trials have... (Review)
Review
Tranexamic acid (TXA) is an important antifibrinolytic agent, which inhibits plasminogen activation and fibrinolysis. Several controlled randomized trials have investigated the role of TXA in preventing or decreasing blood loss across different surgical interventions or medical conditions characterized by excessive bleeding, consistently documenting its effectiveness and safety. Although the first clinical use of TXA dates back to more than 60 years ago, TXA remains the focus of intense research. This narrative review summarizes the more recent results and indications on the clinical use of TXA.
Topics: Tranexamic Acid; Humans; Hemostatics; Antifibrinolytic Agents
PubMed: 38335995
DOI: 10.1055/s-0044-1779632