-
Burns : Journal of the International... Sep 2023Burn injury causes a coagulopathy that is poorly understood. After severe burns, significant fluid losses are managed by aggressive resuscitation that can lead to... (Meta-Analysis)
Meta-Analysis Review
Burn injury causes a coagulopathy that is poorly understood. After severe burns, significant fluid losses are managed by aggressive resuscitation that can lead to hemodilution. These injuries are managed by early excision and grafting, which can cause significant bleeding and further decrease blood cell concentration. Tranexamic acid (TXA) is an anti-fibrinolytic that has been shown to reduce surgical blood losses; however, its use in burn surgery is not well established. We performed a systematic review and meta-analysis to investigate the influence TXA may have on burn surgery outcomes. Eight papers were included, with outcomes considered in a random-effects model meta-analysis. Overall, when compared to the control group, TXA significantly reduced total volume blood loss (mean difference (MD) = -192.44; 95% confidence interval (CI) = -297.73 to - 87.14; P = 0.0003), the ratio of blood loss to burn injury total body surface area (TBSA) (MD = -7.31; 95% CI = -10.77 to -3.84; P 0.0001), blood loss per unit area treated (MD = -0.59; 95% CI = -0.97 to -0.20; P = 0.003), and the number of patients receiving a transfusion intraoperatively (risk difference (RD) = -0.16; 95% CI = -0.32 to - 0.01; P = 0.04). Additionally, there were no noticeable differences in venous thromboembolism (VTE) events (RD = 0.00; 95% CI = -0.03 to 0.03; P = 0.98) and mortality (RD = 0.00; 95% CI = -0.03 to 0.04; P = 0.86). In conclusion, TXA can potentially be a pharmacologic intervention that reduces blood losses and transfusions in burn surgery without increasing the risk of VTE events or mortality.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Venous Thromboembolism; Burns; Blood Loss, Surgical
PubMed: 37268542
DOI: 10.1016/j.burns.2023.05.009 -
The Cochrane Database of Systematic... Oct 2023Outcome after acute spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume. ICH expansion occurs in about 20% of people with acute... (Review)
Review
BACKGROUND
Outcome after acute spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume. ICH expansion occurs in about 20% of people with acute ICH. Early haemostatic therapy might improve outcome by limiting ICH expansion. This is an update of a Cochrane Review first published in 2006, and last updated in 2018.
OBJECTIVES
To examine 1. the effects of individual classes of haemostatic therapies, compared with placebo or open control, in adults with acute spontaneous ICH, and 2. the effects of each class of haemostatic therapy according to the use and type of antithrombotic drug before ICH onset.
SEARCH METHODS
We searched the Cochrane Stroke Trials Register, CENTRAL (2022, Issue 8), MEDLINE Ovid, and Embase Ovid on 12 September 2022. To identify further published, ongoing, and unpublished randomised controlled trials (RCTs), we scanned bibliographies of relevant articles and searched international registers of RCTs in September 2022.
SELECTION CRITERIA
We included RCTs of any haemostatic intervention (i.e. procoagulant treatments such as clotting factor concentrates, antifibrinolytic drugs, platelet transfusion, or agents to reverse the action of antithrombotic drugs) for acute spontaneous ICH, compared with placebo, open control, or an active comparator.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was death/dependence (modified Rankin Scale (mRS) 4 to 6) by day 90. Secondary outcomes were ICH expansion on brain imaging after 24 hours, all serious adverse events, thromboembolic adverse events, death from any cause, quality of life, mood, cognitive function, Barthel Index score, and death or dependence measured on the Extended Glasgow Outcome Scale by day 90.
MAIN RESULTS
We included 20 RCTs involving 4652 participants: nine RCTs of recombinant activated factor VII (rFVIIa) versus placebo/open control (1549 participants), eight RCTs of antifibrinolytic drugs versus placebo/open control (2866 participants), one RCT of platelet transfusion versus open control (190 participants), and two RCTs of prothrombin complex concentrates (PCC) versus fresh frozen plasma (FFP) (47 participants). Four (20%) RCTs were at low risk of bias in all criteria. For rFVIIa versus placebo/open control for spontaneous ICH with or without surgery there was little to no difference in death/dependence by day 90 (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.05; 7 RCTs, 1454 participants; low-certainty evidence). We found little to no difference in ICH expansion between groups (RR 0.81, 95% CI 0.56 to 1.16; 4 RCTs, 220 participants; low-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 0.81, 95% CI 0.30 to 2.22; 2 RCTs, 87 participants; very low-certainty evidence; death from any cause: RR 0.78, 95% CI 0.56 to 1.08; 8 RCTs, 1544 participants; moderate-certainty evidence). For antifibrinolytic drugs versus placebo/open control for spontaneous ICH, there was no difference in death/dependence by day 90 (RR 1.00, 95% CI 0.93 to 1.07; 5 RCTs, 2683 participants; high-certainty evidence). We found a slight reduction in ICH expansion with antifibrinolytic drugs for spontaneous ICH compared to placebo/open control (RR 0.86, 95% CI 0.76 to 0.96; 8 RCTs, 2866 participants; high-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 1.02, 95% CI 0.75 to 1.39; 4 RCTs, 2599 participants; high-certainty evidence; death from any cause: RR 1.02, 95% CI 0.89 to 1.18; 8 RCTs, 2866 participants; high-certainty evidence). There was little to no difference in quality of life, mood, or cognitive function (quality of life: mean difference (MD) 0, 95% CI -0.03 to 0.03; 2 RCTs, 2349 participants; mood: MD 0.30, 95% CI -1.98 to 2.57; 2 RCTs, 2349 participants; cognitive function: MD -0.37, 95% CI -1.40 to 0.66; 1 RCTs, 2325 participants; all high-certainty evidence). Platelet transfusion likely increases death/dependence by day 90 compared to open control for antiplatelet-associated ICH (RR 1.29, 95% CI 1.04 to 1.61; 1 RCT, 190 participants; moderate-certainty evidence). We found little to no difference in ICH expansion between groups (RR 1.32, 95% CI 0.91 to 1.92; 1 RCT, 153 participants; moderate-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 1.46, 95% CI 0.98 to 2.16; 1 RCT, 190 participants; death from any cause: RR 1.42, 95% CI 0.88 to 2.28; 1 RCT, 190 participants; both moderate-certainty evidence). For PCC versus FFP for anticoagulant-associated ICH, the evidence was very uncertain about the effect on death/dependence by day 90, ICH expansion, all serious adverse events, and death from any cause between groups (death/dependence by day 90: RR 1.21, 95% CI 0.76 to 1.90; 1 RCT, 37 participants; ICH expansion: RR 0.54, 95% CI 0.23 to 1.22; 1 RCT, 36 participants; all serious adverse events: RR 0.27, 95% CI 0.02 to 3.74; 1 RCT, 5 participants; death from any cause: RR 0.49, 95% CI 0.16 to 1.56; 2 RCTs, 42 participants; all very low-certainty evidence).
AUTHORS' CONCLUSIONS
In this updated Cochrane Review including 20 RCTs involving 4652 participants, rFVIIa likely results in little to no difference in reducing death or dependence after spontaneous ICH with or without surgery; antifibrinolytic drugs result in little to no difference in reducing death or dependence after spontaneous ICH, but result in a slight reduction in ICH expansion within 24 hours; platelet transfusion likely increases death or dependence after antiplatelet-associated ICH; and the evidence is very uncertain about the effect of PCC compared to FFP on death or dependence after anticoagulant-associated ICH. Thirteen RCTs are ongoing and are likely to increase the certainty of the estimates of treatment effect.
Topics: Adult; Humans; Hemostatics; Antifibrinolytic Agents; Fibrinolytic Agents; Cerebral Hemorrhage; Stroke; Anticoagulants
PubMed: 37870112
DOI: 10.1002/14651858.CD005951.pub5 -
The Journal of Surgical Research Jan 2024The antifibrinolytic tranexamic acid (TXA) may reduce death in trauma; however, outcomes associated with TXA use in patients without proven hyperfibrinolysis remain...
INTRODUCTION
The antifibrinolytic tranexamic acid (TXA) may reduce death in trauma; however, outcomes associated with TXA use in patients without proven hyperfibrinolysis remain unclear. We analyzed the associations of empirically administered TXA, hypothesizing that TXA use would correlate to lower transfusion totals but increased thromboembolic complications.
METHODS
This retrospective cohort study compared trauma patients started on massive transfusion protocol at a Level I trauma center from 2016 to 2021 who either did or did not receive TXA. Our primary outcome was in-hospital mortality. Venous thromboembolism (VTE; pulmonary embolism or deep vein thrombosis), transfusion volumes, and coagulation measures were considered secondarily. Descriptive statistics, univariate analyses, and multivariable logistic regression were used to evaluate differences in outcomes.
RESULTS
TXA patients presented with lower systolic blood pressure (100 versus 119.5 mmHg, P = 0.009), trended toward higher injury severity (ISS of 25 versus 20, P = 0.057), and were likelier to have undergone thoracotomy or laparotomy (89 versus 71%, P = 0.002). After adjusting for age, mechanism, presenting vitals, and operation, TXA was not significantly associated with mortality or VTE. TXA patients had larger volumes of packed red blood cells, platelets, and plasma transfused within 4- and 24-h (P ≤ 0.002). No differences in clot stability, captured via thromboelastography, were noted.
CONCLUSIONS
Despite no differences in mortality or VTE between patients who did and did not receive TXA, there were significant differences in transfusion totals. TXA patients had worse presenting physiology and likely had more severe bleeding. This absence of adverse outcomes supports TXA's safety. Nevertheless, further inquiry into the precise mechanism of TXA may help guide its empiric use, allowing for more targeted application.
Topics: Humans; Tranexamic Acid; Venous Thromboembolism; Retrospective Studies; Antifibrinolytic Agents; Hemorrhage; Blood Loss, Surgical
PubMed: 37839099
DOI: 10.1016/j.jss.2023.08.048 -
Anaesthesia Sep 2023Tranexamic acid is an antifibrinolytic drug that is widely used during surgery, but there are concerns about its thromboembolic effects. We aimed to investigate the... (Meta-Analysis)
Meta-Analysis Review
Tranexamic acid is an antifibrinolytic drug that is widely used during surgery, but there are concerns about its thromboembolic effects. We aimed to investigate the effect of prophylactic intravenous tranexamic acid on thromboembolic outcomes in patients undergoing non-cardiac surgery. The MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched. Randomised controlled trials comparing intravenous tranexamic acid with placebo or no treatment in patients undergoing non-cardiac surgery were included. The primary outcome was a composite of peri-operative cardiovascular thromboembolic events, defined as any deep vein thrombosis, pulmonary embolism, myocardial ischaemia/infarction or cerebral ischaemia/infarction. A total of 191 randomised controlled trials (40,621 patients) were included in the review. The primary outcome occurred in 4.5% of patients receiving intravenous tranexamic acid compared with 4.9% of patients in the control group. Our analysis showed that there was no difference between groups for composite cardiovascular thromboembolic events (risk ratio 1.02, 95%CI 0.94-1.11, p = 0.65, I 0%, n = 37,512). This finding remained robust when sensitivity analysis was performed with continuity correction and in studies with a low risk of bias. However, in trial sequential analysis, our meta-analysis only achieved 64.6% of the required information size. There was no association between intravenous tranexamic acid and seizure rate or mortality rate within 30 days. Intravenous tranexamic acid was associated with a reduced blood transfusion rate compared with control (9.9% vs. 19.4%, risk ratio 0.46, 95%CI 0.41-0.51, p < 0.0001). It was encouraging to see the evidence that the administration of intravenous tranexamic in patients undergoing non-cardiac surgery was not associated with an increased risk of thromboembolic outcomes. However, our trial sequential analysis demonstrated that currently available evidence is not yet sufficient to reach a firm conclusion.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Thromboembolism; Blood Transfusion; Myocardial Infarction; Blood Loss, Surgical
PubMed: 37314744
DOI: 10.1111/anae.16058 -
Current Opinion in Obstetrics &... Apr 2024Tranexamic acid (TXA) has emerged as a promising pharmacological adjunct to treat and prevent postpartum hemorrhage (PPH). We provide an overview of TXA, including its... (Review)
Review
PURPOSE OF REVIEW
Tranexamic acid (TXA) has emerged as a promising pharmacological adjunct to treat and prevent postpartum hemorrhage (PPH). We provide an overview of TXA, including its pharmacology, key findings of randomized trials and observational studies, and critical patient safety information.
RECENT FINDINGS
Pharmacokinetic data indicate that TXA infusions result in peak plasma concentration within 3 min (range: 1-6.6 min). Ex-vivo pharmacodynamic data suggest that low-dose TXA (5 mg/kg) inhibits maximum lysis for at least 1 h. In predominantly developing countries, TXA has demonstrated a 19% reduction in the risk of bleeding-related death among patients with PPH. Based on high-quality randomized trials, TXA prophylaxis does not effectively reduce the risk of PPH during vaginal delivery and is likely ineffective in reducing the PPH risk during cesarean delivery. TXA exposure does not increase the risk of maternal thrombotic events. Maternal deaths have occurred from accidental intrathecal TXA injection from look-alike medication errors.
SUMMARY
TXA has shown promise as an important adjunct for PPH treatment, especially in low-resource settings. However, TXA is not recommended as PPH prophylaxis during vaginal or cesarean delivery. Patient safety initiatives should be prioritized to prevent maternal death from accidental intrathecal TXA injection.
Topics: Pregnancy; Female; Humans; Tranexamic Acid; Antifibrinolytic Agents; Postpartum Hemorrhage; Delivery, Obstetric; Cesarean Section
PubMed: 38170626
DOI: 10.1097/GCO.0000000000000935 -
European Heart Journal. Acute... Oct 2023
Topics: Humans; Fibrin Fibrinogen Degradation Products; Pulmonary Embolism
PubMed: 37707345
DOI: 10.1093/ehjacc/zuad109 -
Anaesthesia, Critical Care & Pain... Aug 2023
Topics: Pregnancy; Female; Humans; Tranexamic Acid; Postpartum Hemorrhage; Antifibrinolytic Agents
PubMed: 37178818
DOI: 10.1016/j.accpm.2023.101241 -
Journal of Ethnopharmacology May 2024Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine prescription for treating ulcerative colitis (UC). However, its potential mechanism of action is...
ETHNOPHARMACOLOGICAL RELEVANCE
Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine prescription for treating ulcerative colitis (UC). However, its potential mechanism of action is still unclear.
AIM OF THE STUDY
Reveal the correlation between the beneficial impacts of BXD on UC and the composition of the gut microbiota.
MATERIALS AND METHODS
The major constituents of BXD were identified using the HPLC-DAD technique. An experimental model of UC was induced in male C57BL/6 mice by administering dextran sodium sulfate (DSS). A total of 48 mice were divided into different groups, including control, model, high-dose BXD treatment, medium-dose BXD treatment, low-dose BXD treatment, and a group treated with 5-amino acid salicylic acid (5-ASA). Body weight changes and disease activity index (DAI) scores were documented; colon length, colon index, spleen index, and thymus index scores were determined; myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) activities were assessed; and histological staining with hematoxylin-eosin and alcian blue/phosphate Schiff was performed. The immunofluorescence technique was employed to examine the presence of ZO-1 and occludin in the colon tissue. 16S rRNA sequencing was employed to assess the gut microbiota's diversity and metabolomics was utilized to examine alterations in metabolites within the gut microbiota. The impact of BXD on the gut microbiota was confirmed through fecal microbiota transplantation (FMT).
RESULTS
BXD exhibited a positive impact on UC mice, particularly in the high-dose BXD treatment group. The BXD group experienced weight recovery, decreased DAI scores, improved colon length, and restored of spleen and thymus index scores compared to the DSS group. Additionally, BXD alleviated colon damage and the inflammatory response while restoring intestinal barrier function. FMT in BXD-treated mice also showed therapeutic effects in UC mice. At the phylum level, the relative abundance of Desulfobacterota, Deferribacterota and Actinobacteriota increased; at the genus level, g__norank__f__Muribaculaceae, Dubosiella, Akkermansia, and Lactobacillus increased, whereas Faecalibaculum, Alloprevotella, Turicibacter, and g_Paraprevotella decreased. g__norank_f__Muribaculaceae was positively correlated with body weight and colon length and negatively with colon index scores, splenic index scores, and MPO levels; Alloprevotella was positively correlated with splenic index scores, histological scores, and TNF-α levels and negatively with thymus index scores and thymus index scores. Faecalibaculum was positively correlated with colon index scores and MPO levels. Metabolic investigations revealed 58 potential indicators, primarily associated with the metabolism of amino acids, purines, and lipids. Alloprevotella, g_Paraprevotella, and Bifidobacterium were strongly associated with metabolic pathways.
CONCLUSION
BXD showed beneficial therapeutic effects in UC mice. The mechanism may be by promoting the balance and variety of gut microbiota, as well as regulating the metabolism of amino acids, purines, and lipids.
Topics: Male; Animals; Mice; Mice, Inbred C57BL; Colitis, Ulcerative; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Tumor Necrosis Factor-alpha; Amino Acids; Antifibrinolytic Agents; Purines; Body Weight; Lipids; Dextran Sulfate; Disease Models, Animal; Colon; Colitis; Drugs, Chinese Herbal
PubMed: 38423412
DOI: 10.1016/j.jep.2024.117990 -
Gastrointestinal Endoscopy Nov 2023Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis.
METHODS
This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy.
RESULTS
Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P = .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P = .023). No adverse events from TXA were recorded.
CONCLUSIONS
The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.).
Topics: Humans; Tranexamic Acid; Male; Hemostasis, Endoscopic; Female; Peptic Ulcer Hemorrhage; Middle Aged; Aged; Antifibrinolytic Agents; Administration, Topical; Treatment Failure; Recurrence; Proton Pump Inhibitors; Stomach Ulcer; Duodenal Ulcer; Adult; Combined Modality Therapy
PubMed: 37356632
DOI: 10.1016/j.gie.2023.06.013 -
Arteriosclerosis, Thrombosis, and... Jul 2023Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and rare complication of acute pulmonary embolism. Mechanisms underlying impaired...
BACKGROUND
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and rare complication of acute pulmonary embolism. Mechanisms underlying impaired clot resolution and in sustained fibrothrombotic obstruction of the pulmonary arterial bed remain poorly understood. Since defective angiogenesis correlated to defective clot resolution based on observations in surgical material from patients with CTEPH, we aimed to validate its crucial pathogenic role by intrathrombus inhibition of angiogenesis in a novel CTEPH rabbit model.
METHODS
We aimed to compare whether intrathrombus administration of an antifibrinolytic agent, tranexamic acid, or an inhibitor of angiogenesis, SU5416, would contribute to CTEPH progression. Both products were administered on a weekly basis by autologous clot embolization in rabbits. Right ventricular pressure was monitored by telemetry, right ventricular function by transthoracic echocardiography, and a complete pulmonary hemodynamic evaluation was obtained through right heart catheterization. Markers of inflammation, endothelial dysfunction, heart failure, and fibrinolysis were measured in plasma. Pulmonary vessel remodeling was analyzed by immunohistochemistry.
RESULTS
Impairing intrathrombus angiogenesis by repeatedly embolizing autologous blood clots containing SU5416 resulted in elevated mean pulmonary arterial pressure (38 mm Hg), increased indexed pulmonary vascular resistance, and enhanced right ventricular hypertrophy (80%, 1.9-fold, 36%, respectively, compared with rabbits embolized with clots containing an antifibrinolytic agent). This was caused by both obstruction of large pulmonary arteries with fibrothrombotic material and muscularization of pulmonary microvessels, and accompanied by inflammatory cell infiltration and increased circulating endothelin-1.
CONCLUSIONS
The key role of angiogenesis-driven clot resolution was validated in a reliable small-animal model reproducing the major pathophysiological hallmarks of CTEPH.
Topics: Animals; Rabbits; Hypertension, Pulmonary; Antifibrinolytic Agents; Pulmonary Artery; Pulmonary Embolism; Thrombosis; Chronic Disease
PubMed: 37165875
DOI: 10.1161/ATVBAHA.122.317262