-
The New England Journal of Medicine Jul 2023Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and suspected trauma-induced coagulopathy who are being treated in advanced trauma systems is uncertain.
METHODS
We randomly assigned adults with major trauma who were at risk for trauma-induced coagulopathy to receive tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. The primary outcome was survival with a favorable functional outcome at 6 months after injury, as assessed with the use of the Glasgow Outcome Scale-Extended (GOS-E). Levels on the GOS-E range from 1 (death) to 8 ("upper good recovery" [no injury-related problems]). We defined survival with a favorable functional outcome as a GOS-E level of 5 ("lower moderate disability") or higher. Secondary outcomes included death from any cause within 28 days and within 6 months after injury.
RESULTS
A total of 1310 patients were recruited by 15 emergency medical services in Australia, New Zealand, and Germany. Of these patients, 661 were assigned to receive tranexamic acid, and 646 were assigned to receive placebo; the trial-group assignment was unknown for 3 patients. Survival with a favorable functional outcome at 6 months occurred in 307 of 572 patients (53.7%) in the tranexamic acid group and in 299 of 559 (53.5%) in the placebo group (risk ratio, 1.00; 95% confidence interval [CI], 0.90 to 1.12; P = 0.95). At 28 days after injury, 113 of 653 patients (17.3%) in the tranexamic acid group and 139 of 637 (21.8%) in the placebo group had died (risk ratio, 0.79; 95% CI, 0.63 to 0.99). By 6 months, 123 of 648 patients (19.0%) in the tranexamic acid group and 144 of 629 (22.9%) in the placebo group had died (risk ratio, 0.83; 95% CI, 0.67 to 1.03). The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups.
CONCLUSIONS
Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo. (Funded by the Australian National Health and Medical Research Council and others; PATCH-Trauma ClinicalTrials.gov number, NCT02187120.).
Topics: Adult; Humans; Antifibrinolytic Agents; Australia; Emergency Medical Services; Tranexamic Acid; Vascular Diseases; Wounds and Injuries; Blood Coagulation Disorders
PubMed: 37314244
DOI: 10.1056/NEJMoa2215457 -
Drug and Therapeutics Bulletin Oct 2023The body needs small daily quantities of vitamins and minerals, which are usually obtained from the diet. Intravenous vitamins are used for a few serious medical... (Review)
Review
The body needs small daily quantities of vitamins and minerals, which are usually obtained from the diet. Intravenous vitamins are used for a few serious medical conditions (eg, malabsorption syndromes with severe vitamin depletion, Wernicke's encephalopathy or critical illness). Intravenous drips containing high doses of various vitamins and minerals (eg, the so-called 'Myers' cocktail') have been promoted in popular culture to 'reduce stress', 'increase energy' or 'boost immunity', with claims that the intravenous route allows faster absorption of vitamins into the bloodstream than if they are taken orally. There is a lack of high-quality evidence to suggest that high-dose vitamin infusions are necessary or offer any health benefit in the absence of a specific vitamin deficiency or medical condition. There may be harms from taking high (non-physiological) quantities of some vitamins and minerals. Licensed forms of injectable vitamins that are prescription-only medicines should not be advertised to the public and should only be supplied and administered by appropriately qualified healthcare professionals.
Topics: Humans; Vitamins; Minerals; Vitamin A; Vitamin K
PubMed: 37640530
DOI: 10.1136/dtb.2023.000006 -
Journal of Thrombosis and Haemostasis :... Dec 2023Fibrinolysis is the system primarily responsible for removal of fibrin deposits and blood clots in the vasculature. The terminal enzyme in the pathway, plasmin, is... (Review)
Review
Fibrinolysis is the system primarily responsible for removal of fibrin deposits and blood clots in the vasculature. The terminal enzyme in the pathway, plasmin, is formed from its circulating precursor, plasminogen. Fibrin is by far the most legendary substrate, but plasmin is notoriously prolific and is known to cleave many other proteins and participate in the activation of other proteolytic systems. Fibrinolysis is often overshadowed by the coagulation system and viewed as a simplistic poorer relation. However, the primordial plasminogen activators evolved alongside the complement system, approximately 70 million years before coagulation saw the light of day. It is highly likely that the plasminogen activation system evolved with its roots in primordial immunity. Almost all immune cells harbor at least one of a dozen plasminogen receptors that allow plasmin formation on the cell surface that in turn modulates immune cell behavior. Similarly, numerous pathogens express their own plasminogen activators or contain surface proteins that provide binding sites for host plasminogen. The fibrinolytic system has been harnessed for clinical medicine for many decades with the development of thrombolytic drugs and antifibrinolytic agents. Our refined understanding and appreciation of the fibrinolytic system and its alliance with infection and immunity and beyond are paving the way for new developments and interest in novel therapeutics and applications. One must ponder as to whether the nomenclature of the system hampered our understanding, by focusing on fibrin, rather than the complex myriad of interactions and substrates of the plasminogen activation system.
Topics: Humans; Fibrinolysis; Fibrinolysin; Plasminogen Activators; Plasminogen; Fibrin; Serine Proteases
PubMed: 38000850
DOI: 10.1016/j.jtha.2023.09.012 -
American Journal of Obstetrics &... Aug 2023Tranexamic acid is a cost-effective intervention for the prevention of postpartum hemorrhage among women who undergo cesarean delivery, but the evidence to support its... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Tranexamic acid is a cost-effective intervention for the prevention of postpartum hemorrhage among women who undergo cesarean delivery, but the evidence to support its use is conflicting. We conducted this meta-analysis to evaluate the efficacy and safety of tranexamic acid in low- and high-risk cesarean deliveries.
DATA SOURCES
We searched MEDLINE (via PubMed), Embase, the Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform portal from inception to April 2022 (updated October 2022 and February 2023) with no language restrictions. In addition, grey literature sources were also explored.
STUDY ELIGIBILITY CRITERIA
All randomized controlled trials that investigated the prophylactic use of intravenous tranexamic acid in addition to standard uterotonic agents among women who underwent cesarean deliveries in comparison with a placebo, standard treatment, or prostaglandins were included in this meta-analysis.
METHODS
We used the revised Cochrane Risk of Bias tool (RoB 2.0) to assess the quality of the included randomized controlled trials. RevMan 5.4 was used to conduct all statistical analyses using a random-effects model.
RESULTS
We included 50 randomized controlled trials (6 in only high-risk patients and 2 with prostaglandins as the comparator) that evaluated tranexamic acid in our meta-analysis. Tranexamic acid reduced the risk for blood loss >1000 mL, the mean total blood loss, and the need for blood transfusion in both low- and high-risk patients. Tranexamic acid was associated with a beneficial effect in the secondary outcomes, including a decline in hemoglobin levels and the need for additional uterotonic agents. Tranexamic acid increased the risk for nonthromboembolic adverse events but, based on limited data, did not increase the incidence of thromboembolic events. The administration of tranexamic acid before skin incision, but not after cord clamping, was associated with a large benefit. The quality of evidence was rated as low to very low for outcomes in the low-risk population and moderate for most outcomes in the high-risk subgroup.
CONCLUSION
Tranexamic acid may reduce the risk for blood loss in cesarean deliveries with a higher benefit observed in high-risk patients, but the lack of high-quality evidence precludes any strong conclusions. The administration of tranexamic acid before skin incision, but not after cord clamping, was associated with a large benefit. Additional studies, especially in the high-risk population and focused on evaluating the timing of tranexamic acid administration, are needed to confirm or refute these findings.
Topics: Humans; Female; Pregnancy; Tranexamic Acid; Blood Loss, Surgical; Cesarean Section; Randomized Controlled Trials as Topic; Postpartum Hemorrhage; Antifibrinolytic Agents; Prostaglandins
PubMed: 37311484
DOI: 10.1016/j.ajogmf.2023.101049 -
Haemophilia : the Official Journal of... Apr 2024Inherited factor coagulation deficiencies and vascular bleeding disorders, associated with bleeding of various severity, are often classified as rare bleeding disorders...
Inherited factor coagulation deficiencies and vascular bleeding disorders, associated with bleeding of various severity, are often classified as rare bleeding disorders (RBDs). These include inherited fibrinogen disorders, inherited platelet function disorders (IPFD) and hereditary haemorrhagic telangiectasia (HHT). In the last decades, there have been large increases in knowledge on the epidemiology, genetics, physiopathology, clinical features, and diagnosis of RBDs, but improvements in management have been more limited and remain challenging. The treatment mainstay of RBDs is based only on replacement of a few available coagulation factor concentrates or cryoprecipitates. There is growing interest in therapeutic agents that enhance coagulation or inhibiting anticoagulant pathways in RBDs. In severe IPFD, the optimal platelet transfusion strategy is not yet established. Moreover, data is scarce on the effectiveness and safety of desmopressin and/or antifibrinolytic drugs often used for milder IPFD treatment. The best fibrinogen replacement strategy (prophylaxis vs. on demand) in afibrinogenemia is still debated. Similarly, the optimal trough fibrinogen target level for treatment of acute bleeding, and the role of fibrinogen replacement during pregnancy in mild hypofibrinogenemia and dysfibrinogenemia, have not been properly evaluated. The therapeutic arsenal in HHT includes antifibrinolytics and a series of antiangiogenic agents whose potential efficacy has been tested in small studies or are under investigation for treatment of bleeding. However, there is need to address several issues, including the optimal dosing strategies, the potential emergent toxicity of longer-term use, and the impact of systemic antiangiogenic treatment on visceral arteriovenous malformations.
Topics: Pregnancy; Female; Humans; Blood Coagulation Disorders; Hemorrhage; Fibrinogen; Blood Coagulation Factors; Afibrinogenemia; Antifibrinolytic Agents
PubMed: 38494995
DOI: 10.1111/hae.14986 -
Revue Medicale Suisse Nov 2023
Topics: Aged; Humans; Anticoagulants; Fibrinolytic Agents; Patients; Vitamin K
PubMed: 37994603
DOI: 10.53738/REVMED.2023.19.851.2226 -
Annual Review of Nutrition Aug 2023Amino acids derived from protein digestion are important nutrients for the growth and maintenance of organisms. Approximately half of the 20 proteinogenic amino acids... (Review)
Review
Amino acids derived from protein digestion are important nutrients for the growth and maintenance of organisms. Approximately half of the 20 proteinogenic amino acids can be synthesized by mammalian organisms, while the other half are essential and must be acquired from the nutrition. Absorption of amino acids is mediated by a set of amino acid transporters together with transport of di- and tripeptides. They provide amino acids for systemic needs and for enterocyte metabolism. Absorption is largely complete at the end of the small intestine. The large intestine mediates the uptake of amino acids derived from bacterial metabolism and endogenous sources. Lack of amino acid transporters and peptide transporter delays the absorption of amino acids and changes sensing and usage of amino acids by the intestine. This can affect metabolic health through amino acid restriction, sensing of amino acids, and production of antimicrobial peptides.
Topics: Humans; Animals; Biological Transport; Intestines; Amino Acids; Nutritional Status; Enterocytes; Antifibrinolytic Agents; Mammals
PubMed: 37285555
DOI: 10.1146/annurev-nutr-061121-094344 -
Stroke Sep 2023Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid... (Randomized Controlled Trial)
Randomized Controlled Trial
Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial.
BACKGROUND
Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH.
METHODS
We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis.
RESULTS
Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; =0.40). There was a signal for interaction with onset-to-treatment time (=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; =0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; =0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation.
CONCLUSIONS
In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH.
REGISTRATION
URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.
Topics: Humans; Female; Aged, 80 and over; Male; Tranexamic Acid; Anticoagulants; Administration, Oral; Cerebral Hemorrhage; Antifibrinolytic Agents; Hemostatics; Hematoma; Thromboembolism
PubMed: 37466000
DOI: 10.1161/STROKEAHA.123.042866 -
Acta Clinica Croatica Aug 2023Tranexamic acid is a synthetic derivative of the amino acid lysine, an antifibrinolytic that is primarily used to reduce bleeding in surgery, trauma, and dental... (Review)
Review
Tranexamic acid is a synthetic derivative of the amino acid lysine, an antifibrinolytic that is primarily used to reduce bleeding in surgery, trauma, and dental procedures. Its anti-inflammatory and anti-angiogenic properties, as well as its ability to suppress melanogenesis have enabled it to be used in dermatology in the treatment of skin conditions such as melasma, acne, post-inflammatory hyperpigmentation, rosacea and angioedema. Tranexamic acid can be used by various routes of administration including oral, topical and intradermal injection, and in combination with other treatment methods. This review article presents evidence for the effectiveness of tranexamic acid in the treatment of various skin disorders.
Topics: Humans; Tranexamic Acid; Dermatology; Antifibrinolytic Agents; Hemorrhage; Melanosis; Skin Diseases; Treatment Outcome
PubMed: 38549597
DOI: 10.20471/acc.2023.62.02.16