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Annals of Neurology Jan 2016Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used... (Review)
Review
Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in-hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid-associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid-associated seizures and by translating scientific findings into therapeutic interventions for patients.
Topics: Animals; Antifibrinolytic Agents; Humans; Seizures; Tranexamic Acid
PubMed: 26580862
DOI: 10.1002/ana.24558 -
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 -
Seminars in Thrombosis and Hemostasis Mar 2017Plasmin is the effector protease of the fibrinolytic system, well known for its involvement in fibrin degradation and clot removal. However, plasmin is also recognized... (Review)
Review
Plasmin is the effector protease of the fibrinolytic system, well known for its involvement in fibrin degradation and clot removal. However, plasmin is also recognized as a potent modulator of immunological processes by directly interacting with various cell types including leukocytes (monocytes, macrophages, and dendritic cells) and cells of the vasculature (endothelial cells, smooth muscle cells) as well as soluble factors of the immune system and components of the extracellular matrix. In fact, the removal of misfolded proteins and maintenance of tissue homeostasis seem to be major physiological functions of plasmin. However, a large body of evidence also suggests that excessive plasmin generation frequently contributes to the pathophysiology of acute and chronic inflammatory processes. Hence, one question arising from the broadening effects of plasmin in physiology is whether antifibrinolytic drugs (i.e., tranexamic acid, epsilon aminocaproic acid, or aprotinin) that target plasmin either directly or indirectly and which are commonly used to prevent or treat bleeding might have unintended consequences on the immune response or on other nonfibrinolytic processes in vivo.
Topics: Antifibrinolytic Agents; Fibrinolysin; Fibrinolysis; Humans
PubMed: 27677178
DOI: 10.1055/s-0036-1586227 -
Journal of Thrombosis and Haemostasis :... Mar 2024Tranexamic acid (TXA) is an antifibrinolytic agent originally developed for the management of bleeding in the setting of postpartum hemorrhage (PPH). Over the last 15... (Review)
Review
Tranexamic acid (TXA) is an antifibrinolytic agent originally developed for the management of bleeding in the setting of postpartum hemorrhage (PPH). Over the last 15 years, there has been accumulating evidence on the use of TXA for the treatment of active bleeding in a variety of clinical contexts. Clinical trials have shown that the efficacy and safety of TXA for the treatment of bleeding differ according to the clinical context in which it is being administered, timing of administration, and dose. Early administration is important for efficacy, particularly in trauma and PPH. Further studies are needed to understand the mechanisms by which TXA provides benefit, optimal modes of administration and dosing, and its effect in some clinical settings, such as spontaneous intracerebral hemorrhage. There is no evidence that TXA increases the risk of thrombotic events in patients with major bleeding overall. However, there is evidence of increased risk of venous thrombosis in patients with gastrointestinal bleeding. There is also evidence of increased risk of seizures with the use of higher doses. This review summarizes the current evidence for the use of TXA for patients with active bleeding and highlights the importance of generating evidence of efficacy and safety of hemostatic interventions specific to the bleeding contexts-as findings from 1 clinical setting may not be generalizable to other contexts-and that of individual patient assessment for bleeding, thrombotic, and other risks, as well as important logistical and other practical considerations, to optimize care and outcomes in these settings.
Topics: Pregnancy; Female; Humans; Tranexamic Acid; Antifibrinolytic Agents; Postpartum Hemorrhage; Thrombosis; Gastrointestinal Hemorrhage
PubMed: 37827378
DOI: 10.1016/j.jtha.2023.10.001 -
Plastic and Reconstructive Surgery Jun 2018Prevention of blood loss is a chief consideration in plastic and reconstructive surgery. The antifibrinolytic drugs tranexamic acid and ε-aminocaproic acid have emerged... (Review)
Review
BACKGROUND
Prevention of blood loss is a chief consideration in plastic and reconstructive surgery. The antifibrinolytic drugs tranexamic acid and ε-aminocaproic acid have emerged as promising agents to reduce both perioperative blood loss and transfusion requirements. However, published reports in the plastic surgery literature are lacking. The authors sought to summarize the current knowledge of the use of antifibrinolytics in plastic surgery by reviewing the existing literature for clinical outcomes and recommendations.
METHODS
A systematic review of the PubMed, Cochrane, and Google Scholar databases was conducted for publications examining the use of antifibrinolytics in plastic surgery. Studies were abstracted for procedure type, antifibrinolytic dose, time and mode of administration, blood loss, transfusion requirements, and complications.
RESULTS
Thirty-three studies were deemed eligible for inclusion, comprising a total of 1823 patients undergoing plastic surgical procedures with tranexamic acid (n = 1328) and/or ε-aminocaproic acid (n = 495).
CONCLUSIONS
Tranexamic acid and ε-aminocaproic acid are widely used to reduce blood loss and transfusion requirements in craniofacial and orthognathic surgery, without an increased risk of adverse events. Intravenous administration is most commonly used, although topical formulations show similar efficacy with a reduced systemic distribution. Tranexamic acid has also emerged as a promising agent in aesthetic surgery and burn care, due to its favorable safety profile and role in reducing blood loss, achieving an improved surgical field, and reducing edema and ecchymosis. Further investigation of these agents in the fields of burn care, aesthetic surgery, and microsurgery is warranted to standardize protocols for clinical use.
Topics: Aminocaproic Acid; Antifibrinolytic Agents; Burns; Clinical Trials as Topic; Cohort Studies; Forecasting; Humans; Microsurgery; Orthognathic Surgical Procedures; Plastic Surgery Procedures; Tranexamic Acid
PubMed: 29794717
DOI: 10.1097/PRS.0000000000004421 -
European Journal of Trauma and... Jun 2016Severe trauma and massive haemorrhage represent the leading cause of death and disability in patients under the age of 45 years in the developed world. Even though much... (Review)
Review
Severe trauma and massive haemorrhage represent the leading cause of death and disability in patients under the age of 45 years in the developed world. Even though much advancement has been made in our understanding of the pathophysiology and management of trauma, outcomes from massive haemorrhage remain poor. This can be partially explained by the development of coagulopathy, acidosis and hypothermia, a pathological process collectively known as the "lethal triad" of trauma. A number of pharmacological adjuncts have been utilised to stop bleeding, with a wide variation in the safety and efficacy profiles. Antifibrinolytic agents in particular, act by inhibiting the conversion of plasminogen to plasmin, therefore decreasing the degree of fibrinolysis. Tranexamic acid, the most commonly used antifibrinolytic agent, has been successfully incorporated into most trauma management protocols effectively reducing mortality and morbidity following trauma. In this review, we discuss the current literature with regard to the management of haemorrhage following trauma, with a special reference to the use of pharmacological adjuncts. Novel insights, concepts and treatment modalities are also discussed.
Topics: Acidosis; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Transfusion; Clinical Protocols; Fibrinolysis; Hemorrhage; Humans; Hypothermia; Multiple Trauma; Tranexamic Acid
PubMed: 26660675
DOI: 10.1007/s00068-015-0613-x -
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 -
Journal of Pediatric Hematology/oncology Apr 2022Children and adolescents undergoing posterior spinal fusion for scoliosis experience high rates of bleeding and blood product transfusion. Antifibrinolytic therapy is... (Review)
Review
Children and adolescents undergoing posterior spinal fusion for scoliosis experience high rates of bleeding and blood product transfusion. Antifibrinolytic therapy is one key strategy to decrease blood loss and transfusion in pediatric scoliosis surgery. Here we review 172 pediatric scoliosis patients (birth to 21 y) who underwent posterior spinal fusion at our institution from 2017 to 2018. We reported rates of blood loss and transfusion, compared patients receiving tranexamic acid to a ε-aminocaproic acid, and evaluated antifibrinolytic agent and laboratory parameters as predictors of blood loss and transfusion. Intraoperatively, 62% received tranexamic acid and 38% received ε-aminocaproic acid. Overall, blood loss (mean intraoperative estimated blood loss=14.9±9.7 mL/kg, 22% with clinically significant blood loss [>20 mL/kg], and mean calculated hemoglobin mass loss=175.9±70.1 g) and transfusion rates (15% with intraoperative allogeneic red blood cell transfusion and mean intraoperative allogeneic red blood cell transfusion volume=12.5±7.1 mL/kg) were similar to previous cohorts studying intraoperative antifibrinolytics. There was no difference in intraoperative estimated blood loss, clinically significant blood loss, calculated hemoglobin mass loss, or transfusion rates between the antifibrinolytic groups. Antifibrinolytic choice was not predictive of blood loss or transfusion. Routine hematologic laboratory parameters and antifibrinolytic choice were insufficient to predict blood loss or other outcomes. Future prospective laboratory-based studies may provide a more comprehensive model of surgical-induced coagulopathy in scoliosis surgery and provide a better tool for predicting blood loss and improving outcomes.
Topics: Adolescent; Aminocaproic Acid; Antifibrinolytic Agents; Blood Loss, Surgical; Child; Humans; Retrospective Studies; Scoliosis; Tranexamic Acid; Treatment Outcome
PubMed: 34654764
DOI: 10.1097/MPH.0000000000002351 -
Current Opinion in Anaesthesiology Jun 2019Perioperative bleeding and blood product transfusion are associated with significant morbidity and mortality. Prevention and optimal management of bleeding decreases... (Review)
Review
PURPOSE OF REVIEW
Perioperative bleeding and blood product transfusion are associated with significant morbidity and mortality. Prevention and optimal management of bleeding decreases risk and lowers costs. Tranexamic acid (TXA) is an antifibrinolytic agent that reduces bleeding and transfusion in a broad number of adult and pediatric surgeries, as well as in trauma and obstetrics. This review highlights the current pediatric indications and contraindications of TXA. The efficacy and safety profile, given current and evolving research, will be covered.
RECENT FINDINGS
Based on the published evidence, prophylactic or therapeutic TXA administration is a well-tolerated and effective strategy to reduce bleeding, decrease allogeneic blood product transfusion, and improve pediatric patients' outcomes. TXA is now recommended in recent guidelines as an important part of pediatric blood management protocols.
SUMMARY
Based on TXA pharmacokinetics, the authors recommend a dosing regimen of between 10 to 30 mg/kg loading dose followed by 5 to 10 mg/kg/h maintenance infusion rate for pediatric trauma and surgery. Maximal efficacy and minimal side-effects with this dosage regime will have to be determined in larger prospective trials including high-risk groups. Furthermore, future research should focus on determining the ideal TXA plasma therapeutic concentration for maximum efficacy and minimal side-effects.
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Child; Dose-Response Relationship, Drug; Humans; Infusions, Intravenous; Perioperative Care; Postoperative Hemorrhage; Practice Guidelines as Topic; Surgical Procedures, Operative; Tranexamic Acid; Transfusion Reaction; Treatment Outcome
PubMed: 30893114
DOI: 10.1097/ACO.0000000000000728 -
Orthopaedics & Traumatology, Surgery &... Jun 2022Periacetabular osteotomy (PAO) is a major hip preservation surgery for developmental dysplasia of the hip. It is inevitably associated with significant blood loss, so it... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periacetabular osteotomy (PAO) is a major hip preservation surgery for developmental dysplasia of the hip. It is inevitably associated with significant blood loss, so it requires frequent transfusions and could be a cause of perioperative morbidity. However, to date, a large number of studies has not evaluated the effect of antifibrinolytic agents in PAO. Therefore we performed a systematic review and meta-analysis to assess if antifibrinolytics would be effective in reducing blood loss and transfusion rate after PAO surgery.
METHODS
In this systematic review and meta-analysis, MEDLINE, Embase, and Cochrane Library databases were systematically searched for studies published before April 4, 2020, that investigated the effect of antifibrinolytic agents in PAO. A pooled analysis was designed to identify differences between antifibrinolytic and control groups focusing on blood loss, transfusion, operation time, postoperative venous thromboembolism (VTE), and length of hospital stay.
RESULTS
We included five studies involving 507 patients (antifibrinolytic group: 256; control group: 251). The pooled analysis showed that the control group had a greater total estimated blood loss (EBL) than the antifibrinolytic group (mean difference [MD]=-257.60mL, 95% confidence interval [CI] -389.68 to -125.53, p=0.0001), but there were no statistical differences in intraoperative EBL (MD=-46.46mL, 95% CI: -192.57 to 99.64, p=0.53). The allogenic transfusion rate was higher in the control group than in the antifibrinolytic group (odds ratio [OR] 0.21, 95% CI: 0.10-0.43, p<0.0001), but there was no difference in the autogenic transfusion rate (OR 0.35, 95% CI: 0.09-1.43, p=0.14). The pooled result showed no difference in operation time (MD=9.13min, 95% CI: -8.54 to 26.80, p=0.31). For the VTE rate, a pooled analysis was not conducted due to the lack of data. The length of hospital stay showed no differences (MD=-0.51 days, 95% CI: -1.17 to 0.16, p=0.13).
CONCLUSIONS
Antifibrinolytic use in PAO has positive effects in terms of reduced total EBL and allogenic transfusion rate.
LEVEL OF EVIDENCE
III; meta-analysis.
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Humans; Osteotomy; Tranexamic Acid; Venous Thromboembolism
PubMed: 35292390
DOI: 10.1016/j.otsr.2022.103271