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Wilderness & Environmental Medicine Jun 2017The use of tranexamic acid (TXA) in the treatment of trauma patients was relatively unexplored until the landmark Clinical Randomisation of an Antifibrinolytic in... (Review)
Review
The use of tranexamic acid (TXA) in the treatment of trauma patients was relatively unexplored until the landmark Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage-2 (CRASH-2) trial in 2010 demonstrated a reduction in mortality with the use of TXA. Although this trial was a randomized, double-blinded, placebo-controlled study incorporating >20,000 patients, numerous limitations and weaknesses have been described. As a result, additional studies have followed, delineating the potential risks and benefits of TXA administration. A systematic review of the literature to date reveals a mortality benefit of early (ideally <1 hour and no later than 3 hours after injury) TXA administration in the treatment of severely injured trauma patients (systolic blood pressure <90 mm Hg, heart rate >110). Combined with abundant literature showing a reduction in bleeding in elective surgery, the most significant benefit may be administration of TXA before the patient goes into shock. Those trials that failed to show a mortality benefit of TXA in the treatment of hemorrhagic shock acknowledged that most patients received blood products before TXA administration, thus confounding the results. Although the use of prehospital TXA in the severely injured trauma patient will become more clear with the trauma studies currently underway, the current literature supports the use of prehospital TXA in this high-risk population. We recommend considering a 1 g TXA bolus en route to definitive care in high-risk patients and withholding subsequent doses until hyperfibrinolysis is confirmed by thromboelastography.
Topics: Antifibrinolytic Agents; Hemorrhage; Humans; Tranexamic Acid
PubMed: 28601210
DOI: 10.1016/j.wem.2016.12.006 -
Current Opinion in Anaesthesiology Apr 2015Optimizing hemostasis with antifibrinolytics is becoming a common surgical practice. Large clinical studies have demonstrated efficacy and safety of tranexamic acid... (Review)
Review
PURPOSE OF REVIEW
Optimizing hemostasis with antifibrinolytics is becoming a common surgical practice. Large clinical studies have demonstrated efficacy and safety of tranexamic acid (TXA) in the trauma population to reduce blood loss and transfusions. Its use in patients without pre-existing coagulopathies is debated, as thromboembolic events are a concern. In this review, perioperative administration of TXA is examined in nontrauma surgical populations. Additionally, risk of thromboembolism, dosing regimens, and timing of dosing are assessed.
RECENT FINDINGS
Perioperative use of TXA is associated with reduced blood loss and transfusions. Thromboembolic effects do not appear to be increased. However, optimal dosing and timing of TXA administration is still under investigation for nontrauma surgical populations.
SUMMARY
As part of a perioperative blood management programme, TXA can be used to help reduce blood loss and mitigate exposure to blood transfusion.
Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Hemostasis; Humans; Perioperative Care; Tranexamic Acid; Wounds and Injuries
PubMed: 25635366
DOI: 10.1097/ACO.0000000000000165 -
The Cochrane Database of Systematic... Jun 2015Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. People with liver disease frequently have... (Review)
Review
BACKGROUND
Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. People with liver disease frequently have haemostatic abnormalities such as hyperfibrinolysis. Therefore, antifibrinolytic amino acids have been proposed to be used as supplementary interventions alongside any of the primary treatments for upper gastrointestinal bleeding in people with liver diseases. This is an update of this Cochrane review.
OBJECTIVES
To assess the beneficial and harmful effects of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease.
SEARCH METHODS
We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), LILACS (1982 to February 2015), World Health Organization Clinical Trials Search Portal (accessed 26 February 2015), and the metaRegister of Controlled Trials (accessed 26 February 2015). We scrutinised the reference lists of the retrieved publications.
SELECTION CRITERIA
Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. Observational studies for assessment of harms.
DATA COLLECTION AND ANALYSIS
We planned to summarise data from randomised clinical trials using standard Cochrane methodologies and assessed according to the GRADE approach.
MAIN RESULTS
We found no randomised clinical trials assessing antifibrinolytic amino acids for treating upper gastrointestinal bleeding in people with acute or chronic liver disease. We did not identify quasi-randomised, historically controlled, or observational studies in which we could assess harms.
AUTHORS' CONCLUSIONS
This updated Cochrane review identified no randomised clinical trials assessing the benefits and harms of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. The benefits and harms of antifibrinolytic amino acids need to be tested in randomised clinical trials. Unless randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver diseases.
Topics: Acute Disease; Amino Acids; Antifibrinolytic Agents; Blood Coagulation Disorders; Chronic Disease; Gastrointestinal Hemorrhage; Humans; Liver Diseases
PubMed: 26058965
DOI: 10.1002/14651858.CD006007.pub4 -
Hamostaseologie Oct 2022In premenopausal women treatment with direct oral anticoagulants (DOACs) can be associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin...
In premenopausal women treatment with direct oral anticoagulants (DOACs) can be associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists. These findings come from retrospective or prospective single-center studies and post hoc analysis of regulatory studies in which HMB was not a predefined safety outcome. In most of these publications, there is a lack of information about the use of different contraceptive methods which can influence HMB. Another limitation is the various definitions of HMB, which makes comparison between studies regarding the incidences of HMB difficult.Therefore, prospective studies are urgently needed to investigate the severity and duration of unaffected menstrual bleeding under oral anticoagulation independently of oral contraceptives or intrauterine devices. An ongoing multicenter German registry is aiming to compare the incidence of unaffected HMB in consecutive women of reproductive age (18-50 years) treated with different DOACs because of venous thromboembolism.When HMB occurs during oral anticoagulation, management includes interruption or dose reduction of anticoagulation with the danger of recurrent venous thrombosis, switch to another oral anticoagulant, or additional use of the antifibrinolytic agent tranexamic acid with the potential risk of thrombosis. Concomitant use of either oral hormonal contraceptive therapy or hormone-releasing intrauterine systems can also reduce HMB.
Topics: Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Prospective Studies; Retrospective Studies; Menorrhagia; Antifibrinolytic Agents; Anticoagulants; Contraceptives, Oral
PubMed: 36323281
DOI: 10.1055/a-1891-8187 -
British Medical Journal Nov 1968
Topics: Afibrinogenemia; Antifibrinolytic Agents; Blood Coagulation; Fibrinogen; Humans
PubMed: 5683576
DOI: No ID Found -
CMAJ : Canadian Medical Association... Oct 2014
Review
Topics: Antifibrinolytic Agents; Canada; Hemorrhage; Humans; Time Factors; Tranexamic Acid; Wounds and Injuries
PubMed: 25047987
DOI: 10.1503/cmaj.131741 -
Anesthesia and Analgesia Feb 2018
Topics: Antifibrinolytic Agents; Ischemic Preconditioning; Tranexamic Acid
PubMed: 29346202
DOI: 10.1213/ANE.0000000000002690 -
International Journal of Molecular... Sep 2023The fibrinolytic system is a key player in keeping the haemostatic balance, and changes in fibrinolytic capacity can lead to both bleeding-related and thrombosis-related... (Review)
Review
The fibrinolytic system is a key player in keeping the haemostatic balance, and changes in fibrinolytic capacity can lead to both bleeding-related and thrombosis-related disorders. Our knowledge of the fibrinolytic system has expanded immensely during the last 75 years. From the first successful use of thrombolysis in myocardial infarction in the 1960s, thrombolytic therapy is now widely implemented and has reformed treatment in vascular medicine, especially ischemic stroke, while antifibrinolytic agents are used routinely in the prevention and treatment of major bleeding worldwide. Despite this, this research field still holds unanswered questions. Accurate and timely laboratory diagnosis of disturbed fibrinolysis in the clinical setting remains a challenge. Furthermore, despite growing evidence that hypofibrinolysis plays a central role in, e.g., sepsis-related coagulopathy, coronary artery disease, and venous thromboembolism, there is currently no approved treatment of hypofibrinolysis in these settings. The present review provides an overview of the fibrinolytic system and history of its discovery; measurement methods; clinical relevance of the fibrinolytic system in diagnosis and treatment; and points to future directions for research.
Topics: Humans; Antifibrinolytic Agents; Clinical Relevance; Coronary Artery Disease; Fibrin Clot Lysis Time; Fibrinolysis
PubMed: 37762481
DOI: 10.3390/ijms241814179 -
Medicinal Research Reviews Nov 2014Growing evidence suggests that plasmin is involved in a number of physiological processes in addition to its key role in fibrin cleavage. Plasmin inhibition is critical... (Review)
Review
Growing evidence suggests that plasmin is involved in a number of physiological processes in addition to its key role in fibrin cleavage. Plasmin inhibition is critical in preventing adverse consequences arising from plasmin overactivity, e.g., blood loss that may follow cardiac surgery. Aprotinin was widely used as an antifibrinolytic drug before its discontinuation in 2008. Tranexamic acid and ε-aminocaproic acid, two small molecule plasmin inhibitors, are currently used in the clinic. Several molecules have been designed utilizing covalent, but reversible, chemistry relying on reactive cyclohexanones, nitrile warheads, and reactive aldehyde peptidomimetics. Other major classes of plasmin inhibitors include the cyclic peptidomimetics and polypeptides of the Kunitz and Kazal-type. Allosteric inhibitors of plasmin have also been designed including small molecule lysine analogs that bind to plasmin's kringle domain(s) and sulfated glycosaminoglycan mimetics that bind to plasmin's catalytic domain. Plasmin inhibitors have also been explored for resolving other disease states including cell metastasis, cell proliferation, angiogenesis, and embryo implantation. This review highlights functional and structural aspects of plasmin inhibitors with the goal of advancing their design.
Topics: Antifibrinolytic Agents; Aprotinin; Benzamidines; Dipeptides; Drug Design; Fibrinolysin; Fibrinolysis; Guanidines; Humans; Phenylalanine; Serine Proteinase Inhibitors
PubMed: 24659483
DOI: 10.1002/med.21315 -
Chinese Medical Journal Mar 2019Significant blood loss is still one of the most frequent complications in spinal surgery, which often necessitates blood transfusion. Massive perioperative blood loss... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Significant blood loss is still one of the most frequent complications in spinal surgery, which often necessitates blood transfusion. Massive perioperative blood loss and blood transfusion can create additional risks. Aprotinin, tranexamic acid (TXA), and epsilon-aminocaproic acid (EACA) are antifibrinolytics currently offered as prophylactic agents to reduce surgery-associated blood loss. The aim of this study was to evaluate the efficacy and safety of aprotinin, EACA, and low/high doses of TXA in spinal surgery, and assess the use of which agent is the most optimal intervention using the network meta-analysis (NMA) method.
METHODS
Five electronic databases were searched, including PubMed, Cochrane Library, ScienceDirect, Embase, and Web of Science, from the inception to March 1, 2018. Trials that were randomized and compared results between TXA, EACA, and placebo were identified. The NMA was conducted with software R 3.3.2 and STATA 14.0.
RESULTS
Thirty randomized controlled trial (RCT) studies were analyzed. Aprotinin (standardized mean difference [SMD]=-0.65, 95% credibility intervals [CrI;-1.25, -0.06]), low-dose TXA (SMD = -0.58, 95% CrI [-0.92, -0.25]), and high-dose TXA (SMD = -0.70, 95% CrI [-1.04, -0.36]) were more effective than the respective placebos in reducing intraoperative blood loss. Low-dose TXA (SMD = -1.90, 95% CrI [-3.32, -0.48]) and high-dose TXA (SMD = -2.31, 95% CrI [-3.75, -0.87]) had less postoperative blood loss. Low-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) and high-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) significantly reduced total blood loss. However, only high-dose TXA (SMD = -2.07, 95% CrI [-3.26, -0.87]) was more effective in reducing the amount of transfusion, and was significantly superior to low-dose TXA in this regard (SMD = -1.67, 95% CrI [-3.20, -0.13]). Furthermore, aprotinin (odds ratio [OR] = 0.16, 95% CrI [0.05, 0.54]), EACA (OR = 0.46, 95% CrI [0.22, 0.97]) and high dose of TXA (OR = 0.34, 95% CrI [0.19, 0.58]) had a significant reduction in transfusion rates. Antifibrinolytics did not show a significantly increased risk of postoperative thrombosis. Results of ranking probabilities indicated that high-dose TXA had the greatest efficacy and a relatively high safety level.
CONCLUSIONS
The antifibrinolytic agents are able to reduce perioperative blood loss and transfusion requirement during spine surgery. And the high-dose TXA administration might be used as the optimal treatment to reduce blood loss and transfusion.
Topics: Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Humans; Randomized Controlled Trials as Topic; Spine; Tranexamic Acid
PubMed: 30807356
DOI: 10.1097/CM9.0000000000000108