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The New England Journal of Medicine Apr 2021
Review
Topics: Antifibrinolytic Agents; Blood Transfusion; Female; Fluid Therapy; Humans; Oxytocics; Postpartum Hemorrhage; Pregnancy; Risk Factors; Tampons, Surgical; Tranexamic Acid; Uterine Inertia; Uterus
PubMed: 33913640
DOI: 10.1056/NEJMra1513247 -
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 -
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 -
Lancet (London, England) Nov 2019Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial.
BACKGROUND
Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI.
METHODS
This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. 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. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277).
RESULTS
Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86-1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80-1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64-0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91-1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74-1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90-1·33]).
INTERPRETATION
Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury.
FUNDING
National Institute for Health Research Health Technology Assessment, JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and Wellcome Trust (Joint Global Health Trials scheme).
TRANSLATIONS
For the Arabic, Chinese, French, Hindi, Japanese, Spanish and Urdu translations of the abstract see Supplementary Material.
Topics: Adult; Aged; Antifibrinolytic Agents; Brain Injuries, Traumatic; Drug Administration Schedule; Female; Humans; Intention to Treat Analysis; International Cooperation; Intracranial Hemorrhage, Traumatic; Male; Middle Aged; Severity of Illness Index; Survival Analysis; Time-to-Treatment; Tranexamic Acid; Treatment Outcome; Vascular Diseases; Young Adult
PubMed: 31623894
DOI: 10.1016/S0140-6736(19)32233-0 -
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 2023Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear.
METHODS
We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed.
RESULTS
A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; P = 0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was -1.8 g per deciliter and -1.9 g per deciliter, respectively (mean difference, -0.1 g per deciliter; 95% CI, -0.2 to -0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups.
CONCLUSIONS
Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.).
Topics: Child; Female; Humans; Pregnancy; Antifibrinolytic Agents; Blood Loss, Surgical; Hemoglobins; Maternal Death; Tranexamic Acid; Postpartum Hemorrhage; Cesarean Section; Blood Transfusion; Chemoprevention
PubMed: 37043652
DOI: 10.1056/NEJMoa2207419 -
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 -
The Lancet. Respiratory Medicine Aug 2020In December, 2019, reports emerged from Wuhan, China, of a severe acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By... (Review)
Review
In December, 2019, reports emerged from Wuhan, China, of a severe acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By the end of April, 2020, over 3 million people had been confirmed infected, with over 1 million in the USA alone, and over 215 000 deaths. The symptoms associated with COVID-19 are diverse, ranging from mild upper respiratory tract symptoms to severe acute respiratory distress syndrome. The major risk factors for severe COVID-19 are shared with idiopathic pulmonary fibrosis (IPF), namely increasing age, male sex, and comorbidities such as hypertension and diabetes. However, the role of antifibrotic therapy in patients with IPF who contract SARS-CoV-2 infection, and the scientific rationale for their continuation or cessation, is poorly defined. Furthermore, several licensed and potential antifibrotic compounds have been assessed in models of acute lung injury and viral pneumonia. Data from previous coronavirus infections such as severe acute respiratory syndrome and Middle East respiratory syndrome, as well as emerging data from the COVID-19 pandemic, suggest there could be substantial fibrotic consequences following SARS-CoV-2 infection. Antifibrotic therapies that are available or in development could have value in preventing severe COVID-19 in patients with IPF, have the potential to treat severe COVID-19 in patients without IPF, and might have a role in preventing fibrosis after SARS-CoV-2 infection.
Topics: Antifibrinolytic Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; Pulmonary Fibrosis; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32422178
DOI: 10.1016/S2213-2600(20)30225-3 -
Blood Feb 2021Hereditary hemorrhagic telangiectasia (HHT) management is evolving because of the emergence and development of antiangiogenic therapies to eliminate bleeding... (Review)
Review
Hereditary hemorrhagic telangiectasia (HHT) management is evolving because of the emergence and development of antiangiogenic therapies to eliminate bleeding telangiectasias and achieve hemostasis. This progress is reflected in recent clinical recommendations published in the Second International Guidelines for the Diagnosis and Treatment of HHT, in which systemic therapies including antiangiogenics and antifibrinolytics are now recommended as standard treatment options for bleeding. This review highlights the new recommendations especially relevant to hematologists in managing bleeding, anticoagulation, and anemia in patients with HHT.
Topics: Anemia; Angiogenesis Inhibitors; Anticoagulants; Antifibrinolytic Agents; Clinical Trials as Topic; Disease Management; Epistaxis; Erythrocyte Transfusion; Forecasting; Gastrointestinal Hemorrhage; Humans; Immunologic Factors; Iron Deficiencies; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prevalence; Standard of Care; Telangiectasia, Hereditary Hemorrhagic; Thrombophilia; Tranexamic Acid
PubMed: 33171488
DOI: 10.1182/blood.2020008739 -
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