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Tranexamic acid in patients with traumatic brain injury: A meta-analysis
Sarhan Boshra, R. M., Abdelrahim, M. E. A., Osama, H.
Revista espanola de anestesiologia y reanimacion. 2024
Abstract
BACKGROUND We performed a meta-analysis to assess the effectiveness and safety of tranexamic acid in patients with traumatic brain injury (TBI). METHODS We searched the literature for articles evaluating the effectiveness and safety of tranexamic acid (TXA) in TBI published between January 2012 and January 2021, and identified 8 studies with a total of 10860 patients: 5660 received TXA and 5200 served as controls. We used a dichotomous or continuous approach with a random or fixed-effect model to assess the efficacy and safety of TXA in TBI, and calculated the mean difference (MD) and odds ratio (OR) with the corresponding 95% confidence interval. RESULTS In patients with TBI, early administration of TXA was associated with a greater relative benefit (MD -2.45; 95% CI = -4.78 to -0.12; p = 0.04) and less total haematoma expansion (MD - 2.52; 95% CI = -4.85 to -0.19; p = 0.03) compared to controls. There were no statistically significant differences in mortality (OR 0.94; 95% CI = 0.85-1.03; p = 0.18), presence of progressive haemorrhage (OR 0.75; 95% CI = 0.56-1.01; p = 0.06), need for neurosurgery (OR 1.15; 95% CI = 0.66-1.98; p = 0.63), high Disability Rating Scale score (OR 0.90; 95% CI = 0.56-1.45; p = 0.68), and incidence of ischaemic or thromboembolic complications (OR 1.34; 95% CI = 0.33-5.46; p = 0.68) between TBI patients treated with TXA and controls. CONCLUSIONS Early administration of TXA in TBI patients may have a greater relative benefit and may inhibit haematoma expansion. There were no significant differences in mortality, presence of progressive haemorrhage, need for neurosurgery, high Disability Rating Scale score, and incidence of ischaemic or thromboembolic complications between TBI patients treated with TXA and controls. Further studies are needed to validate these results.
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Missingness matters: a secondary analysis of thromboelastography measurements from a recent prehospital randomized tranexamic acid clinical trial
Donohue, J. K., Iyanna, N., Lorence, J. M., Brown, J. B., Guyette, F. X., Eastridge, B. J., Nirula, R., Vercruysse, G. A., O'Keeffe, T., Joseph, B., et al
Trauma surgery & acute care open. 2024;9(1):e001346
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Editor's Choice
Abstract
BACKGROUND Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings. METHODS We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p<0.10 on univariate analysis. RESULTS NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs 125 (88, 147), p<0.01), lower prehospital Glascow Coma Score (14 (3, 15) vs 15 (12, 15), p<0.01), greater rates of prehospital intubation (39.4% vs 24.4%, p<0.01) and greater mortality at 30 days (36.4% vs 6.8%, p<0.01). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2), p=0.04). Within a severe prehospital shock cohort (SBP<70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (β=-27.6, 95% CI (-51.3 to -3.9), p=0.02). CONCLUSIONS Missing data, due to the logistical challenges of sampling certain severely injured patients, may be associated with a lack of TEG parameter changes on TXA administration in the primary analysis. Previous demonstration of TXA's survival benefit in patients with severe prehospital shock in tandem with the current findings supports the notion that TXA acts at least partially by improving clot integrity. LEVEL OF EVIDENCE Level II.
PICO Summary
Population
Patients at risk for haemorrhage receiving tranexamic acid before hospitalization, enrolled in the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport (STAAMP) Trial (n= 903).
Intervention
Prehospital tranexamic acid (TXA) (n= 447).
Comparison
Placebo (n= 456).
Outcome
This study was a secondary analysis of the STAAMP trial, comparing patients that received thromboelastography (TEG) (YES-TEG, n= 837) and patients unable to be sampled (NO-TEG, n= 66) to analyze subgroups in which to investigate TEG differences. NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs. 125 (88, 147)), lower prehospital Glascow Coma Score (14 (3, 15) vs. 15 (12, 15)), greater rates of prehospital intubation (39.4% vs. 24.4%) and greater mortality at 30 days (36.4% vs. 6.8%). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs. 1.1 (1.0, 1.2)). Within a severe prehospital shock cohort (SBP< 70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (β= -27.6; 95% CI [-51.3, -3.9].
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Effectiveness of Tranexamic Acid in Trauma Patients: A Systematic Review
Meza Monge, K., Domene, S. S., Diaz Mendoza, D. L., Vidal-Gallardo, A., Alfaro Llique, A. M., Rodriguez, M., Premchandra, P., Anwar Pandya, S., Arruarana, V. S., Aleman Paredes, K., et al
Cureus. 2024;16(1):e52111
Abstract
Tranexamic acid (TXA), a fibrinolytic agent, effectively inhibits plasminogen activation, thereby reducing fibrinolysis and hemorrhage. This study focused on its application in trauma patients undergoing emergency surgery, a critical area due to trauma's significant role in mortality. Our investigation involved a meticulous screening of randomized controlled trials from databases including Scopus, PubMed, Web of Science, and Cochrane. The findings indicate that TXA intervention is promising in enhancing outcomes for trauma patients. However, the drug's effectiveness may vary based on the specific nature of the medical condition. In summary, robust evidence suggests that TXA can diminish blood loss, lower transfusion rates, reduce complications, and improve hemoglobin and hematocrit levels in surgical patients. Consequently, TXA should be considered a crucial medication, readily available to mitigate morbidity and mortality in surgical settings. Future research should explore factors influencing TXA's effectiveness in traumatic brain injury cases and across a broad spectrum of surgical scenarios in diverse patient populations. This would further guide clinicians in refining and optimizing the use of TXA.
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Tranexamic acid in pediatric hemorrhagic trauma
Borgman, M. A., Nishijima, D. K.
The Journal of Trauma and Acute Care Surgery. 2023;94(1S Suppl 1):S36-s40
Abstract
There is strong evidence in adult literature that tranexamic acid (TXA) given within 3 hours from injury is associated with improved outcomes. The evidence for TXA use in injured children is limited to retrospective studies and one prospective observational trial. Two studies in combat settings and one prospective civilian US study have found association with improved mortality. These studies indicate the need for a randomized controlled trial to evaluate the efficacy of TXA in injured children and to clarify appropriate timing, dose and patient selection. Additional research is also necessary to evaluate trauma-induced coagulopathy in children. Recent studies have identified three distinct fibrinolytic phenotypes following trauma (hyperfibrinolysis, physiologic fibrinolysis, and fibrinolytic shutdown), which can be identified with viscohemostatic assays. Whether viscohemostatic assays can appropriately identify children who may benefit or be harmed by TXA is also unknown.
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Efficacy of Tranexamic Acid in the Treatment of Massive Upper Gastrointestinal Bleeding: A Randomized Clinical Trial
Sedaghat M, Iranshahi M, Mardani M, Mesbah N
Cureus. 2023;15(1):e33503
Abstract
Background Upper gastrointestinal bleeding (GIB) is an important cause of emergency ward admission. Antifibrinolytic agents including tranexamic acid (TXA) have been used for controlling GIB. However, there have been concerns regarding the safety and efficacy of TXA in patients with GIB. Thus, in this study, we aimed to determine the efficacy of TXA in the treatment of massive upper GIB. Methodology This double-blind randomized clinical trial was conducted among 86 consecutive patients who were referred to Imam Hossein Hospital in Tehran, Iran from 2018 to 2019 with the chief complaint of massive upper GIB. Patients were chosen to be in the TXA or placebo groups based on a 1:1 allocation using the block randomization method. The rate of rebleeding, need for blood transfusion, hospital stay, adverse effects, and mortality rate were evaluated and compared across the groups. Results Of the 86 patients enrolled in this study, 55.8% (n = 48) were males. The mean age of all patients was 53.1 ± 10.6 years (TXA group: 54.9 ± 11.5 years, and placebo group: 51.4 ± 9.7 years). Rebleeding was seen in 11 (25.6%) patients in the TXA group and in 20 (46.5%) patients in the control group, which was statistically significant (p = 0.043). Blood transfusion was carried out in only three (7%) patients in the TXA group compared with 14 (32.6%) patients in the placebo group (p = 0.003). Six (14%) patients experienced a hospital stay of longer than five days in the TXA group and 15 (34.9%) patients in the control group, which was statistically significant (p = 0.024). There were no significant differences in the mortality rate across both groups (p > 0.05). Conclusions TXA has no effect on mortality associated with severe upper GIB. However, it was associated with a lower rate of rebleeding and hospitalization time, without significant adverse effects.
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Prehospital Tranexamic Acid for Severe Trauma
Gruen, R. L., Mitra, B., Bernard, S. A., McArthur, C. J., Burns, B., Gantner, D. C., Maegele, M., Cameron, P. A., Dicker, B., Forbes, A. B., et al
The New England journal of medicine. 2023
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Editor's Choice
Abstract
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.).
PICO Summary
Population
Adult patients with severe trauma and at risk for trauma induced coagulopathy, enrolled in the PATCH-Trauma trial in 15 emergency medical services in Australia, New Zealand, and Germany (n= 1,310).
Intervention
Tranexamic acid (n= 661).
Comparison
Placebo (n= 646).
Outcome
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, 1.12]. 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, 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, 1.03]. The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups.
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Association of Fibrinolysis Phenotype with Patient Outcomes following Traumatic Brain Injury
Durbin, S., Brito, A., Johnson, A., Cotton, B., Rowell, S., Schreiber, M.
The journal of trauma and acute care surgery. 2023
Abstract
BACKGROUND Impaired coagulation is associated with elevated risk of mortality in trauma patients. Prior studies have demonstrated increased mortality in patients with hyperfibrinolysis (HF) and fibrinolysis shutdown (SD). Additionally, prior studies have demonstrated no effect of tranexamic acid (TXA) on fibrinolysis phenotypes. We examined the association of admission fibrinolysis phenotype with traumatic brain injury (TBI) patient outcomes. METHODS Data were extracted from a placebo-controlled multicenter clinical trial. Patients ≥15 years old with TBI (Glasgow Coma Scale 3-12) and systolic blood pressure ≥ 90 mmHg were randomized in the out-of-hospital setting to receive placebo bolus/placebo infusion (Placebo), 1 gram (g) TXA bolus/1 g TXA infusion (Bolus Maintenance [BM]); or 2 g TXA bolus/placebo infusion (Bolus Only [BO]). Fibrinolysis phenotypes on admission were determined by clot lysis at 30 minutes (LY30): SD ≤0.8%, physiologic 0.9-2.9%, HF ≥3%. Logistic regression was used to control for age, sex, penetrating injury, ISS, maximum head AIS, and TXA treatment group. RESULTS 747 patients met inclusion criteria. Fibrinolysis shutdown was the most common phenotype in all treatment groups and was associated with increased age, ISS and presence of intracranial hemorrhage (ICH). Inpatient mortality was 15.2% for SD and HF, and 10.6% for physiologic (p = 0.49). No differences in mortality, disability rating scale at 6 months, acute kidney injury, acute respiratory distress syndrome, or multi-organ failure were noted between fibrinolysis phenotypes. CONCLUSION SD is the most common phenotype expressed in moderate to severe TBI. In TBI, there is no association between fibrinolysis phenotype and mortality or other major complications. LEVEL OF EVIDENCE diagnostic test/criteria, III.
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Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial
Gruen DS, Brown JB, Guyette FX, Johansson PI, Stensballe J, Li SR, Leeper CM, Eastridge BJ, Nirula R, Vercruysse GA, et al
The journal of trauma and acute care surgery. 2023
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Editor's Choice
Abstract
BACKGROUND In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial. METHODS We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 (PECAM-1) at hospital admission (0 hours) and 12, 24, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors. RESULTS We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and PECAM measured within the first 72 hours of hospital admission were associated with survival at 30 days (P < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] P = 0.001) even after controlling for patient, injury, and prehospital factors (P = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4 ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors (P = 0.03). CONCLUSIONS Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early pre- and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion. LEVEL OF EVIDENCE Level II, Secondary analysis of a prospective randomized trial.
PICO Summary
Population
Injured patients who received prehospital tranexamic acid (TXA) and were at risk for haemorrhage enrolled in the STAAMP randomised controlled trial (n= 766).
Intervention
Abbreviated dose: 1g of TXA (n= 130). Standard dose: 2g of TXA (n= 119). Repeat dose: 3g of TXA (n= 130).
Comparison
Placebo (saline), (n= 383).
Outcome
Blood samples were collected to measure markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 (PECAM-1) at hospital admission and 12, 24, and 72 hours after admission. Lower levels of syndecan-1, TM, and PECAM measured within the first 72 hours of hospital admission were associated with survival at 30 days. At hospital admission (mean ng/mL [IQR]), syndecan-1 was lower in the TXA group than the placebo group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00]) even after controlling for patient, injury, and prehospital factors. For every 1g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4 ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors.
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Tranexamic Acid for Traumatic Injury in the Emergency Setting: A Systematic Review and Bias-Adjusted Meta-Analysis of Randomized Controlled Trials
Fouche, P. F., Stein, C., Nichols, M., Meadley, B., Bendall, J. C., Smith, K., Anderson, D., Doi, S. A.
Annals of emergency medicine. 2023
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Editor's Choice
Abstract
STUDY OBJECTIVE Traumatic injury causes a significant number of deaths due to bleeding. Tranexamic acid (TXA), an antifibrinolytic agent, can reduce bleeding in traumatic injuries and potentially enhance outcomes. Previous reviews suggested potential TXA benefits but did not consider the latest trials. METHODS A systematic review and bias-adjusted meta-analysis were performed to assess TXA's effectiveness in emergency traumatic injury settings by pooling estimates from randomized controlled trials. Researchers searched Medline, Embase, and Cochrane Central for randomized controlled trials comparing TXA's effects to a placebo in emergency trauma cases. The primary endpoint was 1-month mortality. The methodological quality of the trials underwent assessment using the MASTER scale, and the meta-analysis applied the quality-effects method to adjust for methodological quality. RESULTS Seven randomized controlled trials met the set criteria. This meta-analysis indicated an 11% decrease in the death risk at 1 month after TXA use (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.84 to 0.95) with a number needed to treat of 61 to avoid 1 additional death. The meta-analysis also revealed reduced 24-hour mortality (OR 0.76, 95% CI 0.65 to 0.88) for TXA. No compelling evidence of increased vascular occlusive events emerged (OR 0.96, 95% CI 0.73 to 1.27). Subgroup analyses highlighted TXA's effectiveness in general trauma versus traumatic brain injury and survival advantages when administered out-of-hospital versus inhospital. CONCLUSIONS This synthesis demonstrates that TXA use for trauma in emergencies leads to a reduction in 1-month mortality, with no significant evidence of problematic vascular occlusive events. Administering TXA in the out-of-hospital setting is associated with reduced mortality compared to inhospital administration, and less mortality with TXA in systemic trauma is noted compared with traumatic brain injury specifically.
PICO Summary
Population
Patients with traumatic injuries in emergency settings (7 randomised controlled trials).
Intervention
Tranexamic acid (TXA).
Comparison
Placebo.
Outcome
The primary endpoint was 1-month mortality. The meta-analysis indicated an 11% decrease in the death risk at 1 month after TXA use (odds ratio [OR] 0.89; 95% confidence interval (CI) [0.84, 0.95]) with a number needed to treat of 61 to avoid 1 additional death. The meta-analysis also revealed reduced 24-hour mortality (OR 0.76; 95% CI [0.65, 0.88]) for TXA. No compelling evidence of increased vascular occlusive events emerged (OR 0.96; 95% CI [0.73, 1.27]). Subgroup analyses highlighted TXA's effectiveness in general trauma versus traumatic brain injury and survival advantages when administered out-of-hospital versus in-hospital.
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A systematic review and meta-analysis assessing the use of tranexamic acid (TXA) in acute gastrointestinal bleeding
O'Donnell, O., Gallagher, C., Davey, M. G., Coulter, J., Regan, M.
Irish journal of medical science. 2023
Abstract
INTRODUCTION Gastrointestinal bleeding results in significant morbidity, cost and mortality. TXA, an antifibrinolytic agent, has been proposed to reduce mortality; however, many studies report conflicting results. METHODS The aim of the study was to perform the first systematic review and meta-analysis of RCTs to evaluate the efficacy TXA for both upper and lower gastrointestinal bleeding. This was performed per PRISMA guidelines. PubMed, EMBASE, Cochrane and Scopus databases were searched for RCTs. Dichotomous variables were pooled as risk ratios (RR) with 95% confidence intervals (CI) using the MH method with random effects modelling. RESULTS Fourteen RCTs were identified with 14,338 patients and mean age of 58.4 years. 34.9% (n = 5008) were female and 65.1% (n = 9330) male. There was no significant difference in mortality between TXA and placebo (RR 0.86 95% CI (0.74 to 1.00), P: 0.05). The secondary outcomes, similarly, did not yield significant results. These included rebleeding, need for surgical intervention (RR: 0.75 95% CI (0.53, 1.07)), endoscopic intervention (RR: 0.92 95% CI (0.70, 1.22)), transfusion requirement (RR: 1.01 95% CI (0.94, 10.7)) and length of stay (RR: 0.03 95% CI (- 0.03, 0.08)). There was no increased risk of VTE, RR: 1.29 95% CI (0.53, 3.16). One trial (n = 12,009) reported an increased risk of seizure in the TXA group, RR: 1.73 95% CI (1.03-2.93). CONCLUSION TXA does not reduce mortality in patients with acute upper or lower gastrointestinal bleeding and may confer an increased risk of seizures. The authors do not recommend the use of TXA in acute gastrointestinal bleeding.