Early Administration Of Tranexamic Acid Research Articles

Evaluation of the Early Administration of Tranexamic Acid in Geriatric Hip Fractures in the Emergency Department: A Retrospective Study.

Introduction Tranexamic acid (TXA) administration perioperatively has demonstrated efficacy in reducing postoperative drops in hemoglobin levels and the need for transfusions among patients with peritrochanteric hip fractures. This study aims to perform a retrospective analysis to assess the impact on hemoglobin levels by comparing patients with fragility hip fractures who received TXA in the ED, in addition to the standard perioperative TXA dose, with those who did not receive TXA in the ED. Methods This studyretrospectively reviewed 64 patient records from May 2020 to May 2021 at a Level II trauma center that were classified into two groups: patients who received one gram (g) of TXA in the ED, within five hours of injury (new protocol), or patients who received no TXA in the ED (old protocol). The primary outcomes of the study were hemoglobin and adverse events. An independent t-test was performed on continuous variables. A chi-square test was used to analyze noncontinuous variables. Statistical Product and Service Solutions (SPSS, version 25; IBM SPSS Statistics for Windows, Armonk, NY) was used for analysis.Statistical significance was set at a p value < 0.05. Results We measured the difference between hemoglobin on the day of surgery or day zero and on arrival in the ED, which was not statistically significant between the two protocols (p value = 0.322). The difference between hemoglobin levels on postoperative day one and on arrival in the ED was also not statistically significant (p = 0.339). Adverse events were lower in the new protocol but not statistically significant between the two protocols (p = 0.178). Conclusion Our study showed improved outcomes in postoperative hemoglobin with early administration of TXA in the ED. This is demonstrated by continuous higher postoperative hemoglobin in the new protocol group without an increase in adverse events. While the data did not achieve statistical significance, we believe there is clinical benefit in the early administration of TXA in the ED, a finding that continues to be explored and supported in the literature.

Tranexamic Acid in Trauma Management: A Review of Evidence

Hemorrhage is the leading cause of death in trauma patients and trauma induced coagulopathy (TIC) is a major contributor to bleeding mortality. TIC has a diverse pathophysiology triggered by injury and hypoperfusion, including platelet dysfunction, endotheliopathy, fibrinogen or thrombin abnormalities, and dysregulated fibrinolysis. Early fluid resuscitation, appropriate blood transfusion, and definitive control of bleeding are essential components of initial management for TIC. Additionally, tranexamic acid (TXA), an antifibrinolytic agent, has emerged as a potential adjunctive therapy following the 2010 landmark trial that demonstrated the benefit of early administration of TXA in reducing trauma patient mortality (CRASH-2). This review provides an analysis of the current literature on the use of TXA in trauma patients. It critically evaluates the evidence on the effect of TXA on TIC and other clinical outcomes, emphasizing the time-sensitive nature of TXA administration and the variation of its effect depending on the severity and location of injury. It also discusses the optimal dosage, timing, and safety of TXA, as well as the challenges and limitations of existing studies. Furthermore, it highlights the importance of individualized treatment approaches based on the fibrinolysis status of TIC and the value of goal-directed therapy guided by viscoelastic hemostatic assays for the appropriate use of TXA.

Possible effect of the early administration of tranexamic acid on myocardial injury in patients with severe trauma

Hemodynamic stabilization plays a crucial role in the treatment of patients suffering from severe trauma. Current guidelines recommend the early administration of tranexamic acid (TXA) for bleeding control. While less blood loss can result in less end-organ damage, including myocardial injury, TXA also exhibits prothrombotic effects with potentially adverse myocardial effects. The aim of this study was to investigate the association between the administration of TXA and myocardial injury in patients with severe trauma. We conducted a monocentric cohort study including severely injured patients ≥ 18 years [defined by Injury severity score (ISS) ≥ 16], who were admitted to a tertiary care hospital between 2016 and 2019. Primary outcome measure was myocardial injury according to the fourth Universal Definition (= high sensitive troponin T ≥ 14 ng/l). Secondary endpoints were in-hospital major adverse cardiovascular events (MACE) and mortality. Main exposure was defined as administration of TXA during prehospital period. We conducted multivariate logistic regression models including predefined covariables. A total of 368 patients were screened. Among the 297 included patients (72% male, age. 55?21 years), 119 (40%) presented myocardial injury at hospital arrival. TXA was administered to 20/297 (7%) patients in the prehospital setting, and in 96/297 (32%) patients during pre-or in-hospital period. MACE incidence was 9% (26/297) and in-hospital mortality was 26% (76/297). The adjusted odds ratios (OR) for prehospital TXA and myocardial injury, MACE and mortality were 0.75 [95% confidence interval (CI): 0.25–2.23], 0.51 [95%CI: 0.06–4.30] and 0.84 [0.21–3.33], respectively. In the present cohort of patients suffering from severe trauma, prehospital TXA did not affect the incidence of myocardial injury.

EFFECTS OF TRANEXAMIC ACID ON NEUROPATHOLOGY, ELECTROENCEPHALOGRAPHY, AND CEREBRAL FIBRIN DEPOSITION IN A RAT MODEL OF POLYTRAUMA WITH CONCOMITANT PENETRATING TRAUMATIC BRAIN INJURY.

Several studies have demonstrated the clinical utility of tranexamic acid (TXA) for use in trauma patients presenting with significant hemorrhage. Tranexamic acid is an antifibrinolytic that inhibits plasminogen activation, and plasmin activity has been shown to mitigate blood loss and reduce all-cause mortality in the absence of adverse vascular occlusive events. Recent clinical developments indicate TXA is safe to use in patients with concomitant traumatic brain injury (TBI); however, the prehospital effects are not well understood. Importantly, TXA has been associated with seizure activity. Therefore, this study sought to evaluate the effects of early administration of TXA on neurological recovery and electroencephalogram (EEG) abnormalities following penetrating TBI with concomitant hypoxemia and hemorrhagic shock. We hypothesized that early administration of TXA will provide hemodynamic stabilization and reduce intracerebral hemorrhage, which will result in improved neurological function. To test this hypothesis, Sprague-Dawley rats received a unilateral, frontal penetrating ballistic-like brain injury by inserting a probe into the frontal cortex of the anesthetized rat. Five minutes following brain injury, animals underwent 30 min of respiratory distress and 30 min of hemorrhage. Upon completion of the hemorrhage phase, animals received the initial dose of drug intravenously over 10 min after which the prehospital phase was initiated. During the prehospital phase, animals received autologous shed whole blood as needed to maintain a MAP of 65 mm Hg. After 90 min, "in-hospital" resuscitation was performed by administering the remaining shed whole blood providing 100% oxygen for 15 min. Upon recovery from surgery, animals were administered their second dose of vehicle or TXA intravenously over 8 h. Tranexamic acid induced an early improvement in neurologic deficit, which was statistically significant compared with vehicle at 24, 48, and 72 h at three doses tested. Analysis of cerebral hemoglobin content and intracerebral lesion progression revealed 100 mg/kg provided the optimal effects for improvement of neuropathology and was continued for determination of adverse treatment effects. We observed no exacerbation of cerebral thrombosis, but TXA treatment caused an increased risk of EEG abnormalities. These results suggest that TXA following polytrauma with concomitant brain injury may provide mild neuroprotective effects by preventing lesion progression, but this may be associated with an increased risk of abnormal EEG patterns. This risk may be associated with TXA inhibition of glycine receptors and may warrant additional considerations during the use of TXA in patients with severe TBI.

External Hemorrhage Control Techniques for Human Space Exploration: Lessons from the Battlefield.

The past few decades of military experience have brought major advances in the prehospital care of patients with trauma. A focus on early hemorrhage control with aggressive use of tourniquets and hemostatic gauze is now generally accepted. This narrative literature review aims to discuss external hemorrhage control and the applicability of military concepts in space exploration. In space, environmental hazards, spacesuit removal, and limited crew training could cause significant time delays in providing initial trauma care. Cardiovascular and hematological adaptations to the microgravity environment are likely to reduce the ability to compensate, and resources for advanced resuscitation are limited. Any unscheduled emergency evacuation requires a patient to don a spacesuit, involves exposure to high G-forces upon re-entry into Earth's atmosphere, and costs a significant amount of time until a definitive care facility is reached. As a result, early hemorrhage control in space is critical. Safe implementation of hemostatic dressings and tourniquets seems feasible, but adequate training will be essential, and tourniquets are preferably converted to other methods of hemostasis in case of a prolonged medical evacuation. Other emerging approaches such as early tranexamic acid administration and more advanced techniques have shown promising results as well. For future exploration missions to the Moon and Mars, when evacuation is not possible, we look into what training or assistance tools would be helpful in managing the bleed at the point of injury.

Should pre-hospital intramuscular tranexamic acid be given to trauma patients at risk of significant haemorrhage?

There are situations in the pre-hospital setting where gaining intravenous or intraosseous access is impossible or delayed. This can delay the administration of tranexamic acid to bleeding trauma patients, which may reduce its effectiveness. We sought to investigate whether some patients would benefit from early administration of tranexamic acid via the intramuscular route. Relevant observational and interventional studies were identified and summarised using a BestBET format. The current evidence supports clinicians considering intramuscular tranexamic acid in trauma patients at risk of haemorrhage when there may be significant delay in administration via intravenous or intraosseous routes.

A descriptive analysis of the Canadian prehospital and transport transfusion (CAN-PATT) network

ObjectiveOut-of-hospital blood transfusion (OHBT) is becoming increasingly common across the prehospital environment, yet there is significant variability in OHBT practices. The Canadian Prehospital and Transport Transfusion (CAN-PATT) network was established to collaborate, standardize, and evaluate the effectiveness of out-of-hospital blood transfusion (OHBT) across Canada. The objectives of this study are to describe the setting and organizational characteristics of CAN-PATT member organizations and to provide a cross-sectional examination of the current OHBT practices of CAN-PATT organizations. MethodsThis was a cross-sectional examination of all six critical care transport organizations that are involved in CAN-PATT network. Surveys were sent to identified leads from each organization. The survey focused on three main areas of interest: 1) critical care transport organizational service and coverage, 2) provider, and crew configurations, and 3) OHBT transfusion practices. ResultsAll six surveys were completed and returned. There are a total of 30 critical care transport bases (19 rotor-wing, 20 fixed-wing and 6 land) across Canada and 11 bases have a blood-on-board program. Crew configurations very between organizations as either dual paramedic or paramedic/nurse teams. Median transport times range from 30 to 46 minutes for rotor-wing assets and 64 to 90 minutes for fixed-wing assets. Half of the CAN-PATT organizations started their out-of-hospital blood transfusion programs within the last three years. Most organizations carry at least two units of O-negative, K-negative red blood cells and some organizations also carry group A thawed plasma, fibrinogen concentrate and/or prothrombin complex concentrate. All organizations advocate for early administration of tranexamic acid for injured patients suspected of bleeding. All organizations return un-transfused blood components to their local transfusion medicine laboratory within a predefined timeframe to reduce wastage. ConclusionsVariations in OHBT practices were identified and we have suggested considerations for standardization of transfusion practices and patient care as it relates to OHBT. This standardization will also enable a robust means of data collection to study and optimize outcomes of patients receiving OHBT. A fulsome description of the participating organizations within CAN-PATT should enhance interpretation of future OHBT studies that will be conducted by this network.

Efficacy and Safety of Tranexamic Acid in Preventing Rebleeding after Subarachnoid Hemorrhage: A Randomized Controlled Trial

Background: Recent studies have indicated that early, short-course therapy with Tranexamic Acid (TXA) along with standard treatment for prevention of ischemia in aneurysmal Subarachnoid Hemorrhage (SAH) may be beneficial in preventing rebleeding and improving outcome. The study aimed to assess the efficacy and safety of short-course early administration of TXA combined with standard treatment to prevent rebleeding after SAH.&#x0D; Materials and methods: Seventy-four patients suffering from SAH verified on Computed Tomography (CT) scan within 72 hours after the primary hemorrhage were randomized into two treatment arms [37 received TXA and standard treatment (Experimental group), 37 received standard treatments only (Control group)]. TXA 1 gm was given intravenously slowly over 10 minutes, followed by 1 gm iv eight hourly up to a maximum of 72 hours. They were followed up for one month to observe rebleeding and outcome by Glasgow Outcome Scale.&#x0D; Results: Effective sample size was 70 (35 in TXA, 35 in the no-TXA group) due to the dropout of 4 patients. Out of 70 patients, 21 (30%) had rebleeding, and most of the rebleeding (95.23%) occurred after 72 hours of the initial event. Patients who had rebleeding had comparably lower GCS scores at presentation. Out of 21 rebleeding cases, 20 (95.23%) died within one month from the symptom onset. There was no significant difference (p=0.434) in rebleeding rate in TXA-treated patients (25.7%) versus non-TXA patients (34.3%). Treatment with TXA had no beneficial effect on one-month outcome (p&gt;0.05).The adverse events were similar in the two groups and none of the patients had a seizure.&#x0D; Conclusions: Early short course TXA was tolerable as add-on to standard treatment of SAH but had no significant beneficial effect in reducing rebleeding and in improving one-month outcome.&#x0D; Chatt Maa Shi Hosp Med Coll J; Vol.21 (2); July 2022; Page 25-29

281 Out-of-Hospital TXA Administration Opportunities in Trauma Patients Transported by ALS Ground EMS - A Descriptive Study

As many as 30% of severely injured trauma patients demonstrate evidence of acute coagulopathy of trauma (ACOT) at the time of ED admission. Early administration of tranexamic acid (TXA) may improve patient outcomes with ACOT. Within our system, TXA is currently available only to helicopter EMS (HEMS) units. The purpose of the current study was to determine whether there was a cohort of trauma patients transported by ground EMS (GEMS) who might benefit from out-of-hospital TXA administration.

Estimated Cost-Effectiveness of Implementing a Statewide Tranexamic Acid Protocol for the Management of Suspected Hemorrhage in the Prehospital Setting

Introduction: Hemorrhage is responsible for up to 40% of all traumatic deaths. The seminal CRASH-2 trial demonstrated a reduction in overall mortality following early tranexamic acid (TXA) administration to bleeding trauma patients. Following publication of the trial results, TXA has been incorporated into many prehospital trauma protocols. However, the cost-effectiveness of widespread TXA adoption by EMS is unknown. Objective: To estimate the cost-effectiveness of statewide implementation of a TXA protocol. Methods: The North Carolina Trauma Registry was queried to identify potential TXA patients using the a priori criteria of age ≥18 years, suspected hemorrhage, penetrating or blunt injury, and prehospital blood pressure <90 mmHg and heart rate >110 bpm. Using life tables adjusted for age, sex, and race, and the absolute risk reductions in mortality with early TXA administration reported in the literature, the life-years gained were calculated for each potential life saved. Implementation costs consisted of initial stocking, training, and replacement costs. Projected reduction in hospitalization costs were based on estimates reported in the literature. Economic analyses were conducted from societal and state EMS system perspectives. To assess the robustness of the model, univariate and bivariate sensitivity analyses were performed on selected input variables. Results: Based on the TXA inclusionary criteria, 159 patients could potentially receive TXA per year. In the base-case scenario with a projected absolute mortality reduction of 3%, an additional 4.8 lives per year in NC would be saved, with an estimated 191 total life-years gained. The statewide implementation and operation cost was $305,122 in year 1, and continued operating costs were $6,042 in years 2 and 3, yielding a cost per life saved of $63,967 in year 1 and $1,267 in years 2 and 3. The cost per life-year gained was $1,595 in year 1 and $32 in years 2 and 3. Annual hospitalization costs would potentially be reduced by $1,828,072. Conclusion: Previous studies have demonstrated the clinical effectiveness of early TXA administration to patients with hemorrhage. Our modeling of the financial implications and clinical benefits of implementing a statewide TXA protocol suggests that prehospital TXA is a cost-effective treatment.

Effect of early administration of tranexamic acid on ongoing haemorrhage in dogs with non-surgically treated haemoabdomen.

Tranexamic acid (TXA) is an antifibrinolytic drug used for the prophylaxis and treatment of haemorrhage of various origin. This retrospective study investigated the effect of TXA on ongoing bleeding in dogs with nonsurgically treated haemoabdomen. The study population consisted of 48 dogs treated in the period 2009-2020 at the Small Animal Clinic of the Vetsuisse Faculty of Zurich. Twenty-eight of 48 dogs were treated with 20 mg/kg TXA IV within 3h of diagnosis of haemoabdomen. Dogs treated with and without TXA were monitored over 48 hours for signs of ongoing haemorrhage. Ongoing haemorrhage was defined as an increase in abdominal fluid accumulation, a decrease in haematocrit of >5% over time or need for surgical exploration after at least 12 hours of medical treatment. Transfusion requirements, cumulative amount of fluid therapy, heart rate, respiratory rate, temperature, systolic and mean arterial pressure, estimate of abdominal fluid identified by FAST analysis, venous haematocrit, abdominal haematocrit, serum albumin, serum lactate and thrombocyte count were extracted from patient records at 6, 12, 24 and 48 hours after diagnosis of haemoabdomen. Groups were comparable at presentation, however dogs of the TXA group showed a significantly lower abdominal haematocrit at presentation (37 vs 45%, P=0,034) and a higher fluid accumulation (P=0,019), both persisting over time. None of the outcome parameters for ongoing haemorrhage was significantly different between groups. Transfusion requirement was low and similar in both groups. Of interest, none of the 16 dogs undergoing thromboelastometry showed hyperfibrinolysis at presentation. We conclude that other mechanisms than antifibrinolytic therapy was responsible for cessation of bleeding in the majority of patients.

Implementation of a Guideline of Early Administration of Tranexamic Acid for Severe Primary Postpartum Hemorrhage: A Retrospective Comparative Study

(Aust N Z J Obstet Gynaecol. 2021;61:354–359. [Epub December 22, 2020]) Severe postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide. Tranexamic acid (TXA) is commonly administered to nonobstetric patients to help manage hemorrhage. The World Maternal Antifibrinolytic (WOMAN) trial conducted in women with PPH reported that TXA had no effect on all-cause mortality; however, the trial mostly conducted in low-resource settings. This study aimed to determine whether administering 1 g of TXA intravenously during active PPH (blood loss ≥1000 mL) impacted the rate of maternal morbidity.

Risk of Mortality among Patients with Gastrointestinal Bleeding with Early and Late Treatment with Tranexamic Acid: A Population-Based Cohort Study.

Tranexamic acid (TXA) is an antifibrinolytic pharmacological agent, but its use in gastrointestinal bleeding remains contentious. Moreover, studies on the timing of TXA administration are limited. We examined whether early TXA administration reduced the risk of mortality in patients with gastrointestinal bleeding in a Taiwanese population. We used the National Health Insurance Research Database to identify patients diagnosed with gastrointestinal bleeding with early and late TXA treatment. We defined early treatment as initial TXA treatment in an emergency department and late treatment as initial TXA treatment after hospitalization. Mortality within 52 weeks was the primary outcome. A multivariable analysis using a multiple Cox regression model was applied for data analysis. Propensity score matching (PSM) was performed to reduce the potential for bias caused by measured confounding variables. Of the 52,949 selected patients with gastrointestinal bleeding, 5127 were assigned to either an early or late TXA treatment group after PSM. The incidence of mortality was significantly decreased during the first and fourth weeks (adjusted HR (aHR): 0.65, 95% CI: 0.56–0.75). A Kaplan–Meier curve revealed a significant decrease in cumulative incidence of mortality in the early TXA treatment group (log-rank test: p < 0.0001). Multiple Cox regression analysis revealed significantly lower mortality in the early TXA treatment group compared with the late treatment group (aHR: 0.64, 95% CI: 0.57–0.73). Thromboembolic events were not significantly associated with early or late TXA treatment (aHR: 1.03, 95% CI: 0.94–1.12). A Kaplan–Meier curve also revealed no significant difference in either venous or arterial events (log-rank test: p = 0.3654 and 0.0975, respectively). In conclusion, early TXA treatment was associated with a reduced risk of mortality in patients with gastrointestinal bleeding compared with late treatment, without an increase in thromboembolic events. The risk of rebleeding and need for urgent endoscopic intervention require further randomized clinical trials.

Tranexamic acid for the treatment of postpartum hemorrhage: a cost-effectiveness analysis

Postpartum hemorrhage is a leading cause of pregnancy-related morbidity and mortality. Recent data have demonstrated that tranexamic acid reduces death because of bleeding when used as a treatment for postpartum hemorrhage. The World Health Organization now recommends tranexamic acid as a first-line treatment for postpartum hemorrhage; however, data are not yet available on the frequency of use in the United States, where tranexamic acid is currently recognized as an adjunct treatment for postpartum hemorrhage. We aimed to strengthen the current evidence that tranexamic acid should be recognized as a first-line treatment for postpartum hemorrhage, even in high-resource countries. Furthermore, we aimed to determine whether early administration of tranexamic acid (within 3 hours of diagnosis) is a cost-effective strategy for reducing maternal morbidity and mortality from postpartum hemorrhage in the United States. A decision-analytical model was designed to compare the outcomes and costs of the administration of tranexamic acid in the treatment of postpartum hemorrhage. Moreover, this model was used to compare outcomes for early administration with those of routine use. The interventions compared were 1 g of intravenous tranexamic acid or matching placebo. The risks analyzed in the model were death because of hemorrhage and laparotomy to control bleeding. Probabilities, utilities, and costs were derived from literature. Quality-adjusted life-years were calculated using a discounted life expectancy rate of 3%. Cost-effectiveness was determined on the basis of a willingness-to-pay threshold of $100,000 per quality-adjusted life year. The administration of tranexamic acid to a theoretical cohort of 100,000 women would prevent 11 maternal deaths, 6 postpartum laparotomies after vaginal delivery, and 112 reoperations after cesarean delivery. This would lead to an increase in 329 quality-adjusted life years and a total cost savings of $15.39 million. Furthermore, if tranexamic acid were administered early (within 3 hours of postpartum hemorrhage diagnosis) to the same theoretical cohort, 16 maternal deaths owing to hemorrhage, 9 laparotomies, and 155 reoperations would be prevented. This amounts to an increase in 438 quality-adjusted life years and an annual cost savings of $23.15 million. A sensitivity analysis showed that the administration of tranexamic acid was the dominant strategy at all probabilities of maternal death owing to hemorrhage >0.00002. When the cost of tranexamic acid was varied, the administration of tranexamic acid remained dominant up to a cost of $267 per administration in the United States if given within the first 3 hours. Furthermore, in a Monte Carlo probabilistic sensitivity analysis, the early administration of tranexamic acid remained the dominant strategy (both lowered costs and improved outcomes) in 99.8% of models. Early administration of tranexamic acid was a cost-effective strategy for reducing maternal morbidity and mortality owing to postpartum hemorrhage in the United States.

The effect of tranexamic acid dosing regimen on trauma/hemorrhagic shock-related glycocalyx degradation and endothelial barrier permeability: An in vitro model.

Improved outcomes with early tranexamic acid (TXA) following trauma hemorrhagic shock (T/HS) may be related to its antifibrinolytic, as well as anti-inflammatory properties. Previous in vitro studies have shown that early TXA administration protects against T/HS endothelial barrier dysfunction and associated glycocalyx degradation. An intact endothelial glycocalyx may protect against subsequent neutrophil mediated tissue injury. We postulated that early TXA administration would mitigate against glycocalyx damage and resultant neutrophil adherence and transmigration through the endothelial barrier. This was studied in vitro using a microfluidic flow platform. Human umbilical vein endothelial cell monolayers were subjected to control or shock conditions (hypoxia + epinephrine) followed by administration of TXA 90 minutes or 180 minutes later. "Early" TXA administration protected against glycocalyx degradation, biomarkers of increased permeability and the development of a fibrinolytic phenotype. This was associated with decreased neutrophil endothelial adherence and transmigration. There were no differences in low versus high TXA concentrations. The protective effects were only significant with "early" TXA administration. There was a concentration and temporal effect of TXA administration on endothelial glycocalyx degradation. This was associated with "vascular leakiness" as indexed by the relative ratio of Ang-2/1 and polymorphonuclear neutrophil transmigration. Tranexamic acid if administered in patients with T/HS should be administered "early"; this includes in the prehospital setting.

Efficacy and Safety of Tranexamic Acid Administration in Patients with Acute Traumatic Brain Injury: A Review of Current Literature

Hypothesis: Early administration of tranexamic acid (TXA) reduces mortality in patients suffering from acute traumatic brain injury (TBI). Methods: A structured search of PubMed and CENTRAL from inception until July 1st, 2022 was carried out seeking RCTs comparing the effects of TXA administration to placebo in patients suffering from TBI. The primary outcome tested was 28-day all-cause mortality. Secondary outcomes included intracranial hemorrhage growth and thromboembolic events. Results: Eight RCTs involving a total of 14,714 patients met the inclusion criteria; 7573 patients received TXA while 7141 patients received a placebo. There were 1415 patient deaths (18.7%) in the TXA group and 1410 patient deaths (19.7%) in the placebo group. None of the included studies reported a significant reduction in 28-day all-cause mortality, however, they all shared positive trends toward superior outcomes in the intervention arms. Two of the included studies reported significant reductions in intracranial hemorrhage expansion in those patients treated with TXA, with four more studies reporting trends toward superior outcomes in the TXA groups. There was no evidence of increased incidence of thromboembolic events in the TXA groups in four of the five studies that reported relevant data, with one study representing 1.2% of total patients reporting an increased incidence of pulmonary emboli in the intervention group. Conclusions: In patients suffering from acute TBI, early administration of TXA reduces intracranial hemorrhage growth and may have positive effects on mortality with no corresponding increase in thromboembolic events. Given these results, early administration of TXA in patients experiencing TBI is recommended in initial care. Keywords: Tranexamic acid, Traumatic brain injury, Intracranial hemorrhage, Mortality, Disability

The effect of early tranexamic acid administration on hemoglobin levels after unstable pelvic fracture: An experimental study in rats

Aim: To investigate the effect of early systemic tranexamic acid (TRA) administration on hemoglobin (Hb) levels in rats with pelvic fracture. Method: In our study, 30 Wistar Albino rats were randomly divided into 3 groups in equal numbers and their hemoglobin levels were measured by taking blood samples from each. No trauma was applied to the first group and it was taken as the main control group of the study. Closed bilateral unstable pelvic fractures were created in all rats in groups 2 and 3. Fracture creation time is considered as minute 0. 10 minutes after the fracture was formed, TRA was given to the 1st group, TRA to the 2nd group and saline solution to the 3rd group systemically. Hemoglobin levels were measured by taking blood samples from all rats at 30th minute and 24th hour. The initial Hb values ​​obtained were normalized to 100 and the percentages of 30th minute and 24th hour values ​​were calculated. The initial, 30th minute and 24th hour values ​​of all groups were compared statistically with each other. The 30th minute and 24th hour values ​​were compared statistically between the groups. Results: No death was observed within 24 hours in all three groups. When the first Hb values ​​of each group are normalized to 100, the mean Hb percentages were calculated in the first group as 99.54 and 99.84 at 30 minutes and 24 hour, respectively; 92.95 and 87.73 in the second group; and 87.95 and 73.16 in the third group. When these values ​​obtained were compared statistically within the groups (initial, 30th minute, 24th hour Hb percentages), there was no significant difference between the initial, 30th minute and 24th hour values ​​in group 1. However, a statistically significant difference was found between the initial, 30th minute and 24th hour values ​​in group 2 and 3 (p<0.01). In the comparison between the groups, a statistically significant difference was found between group 1-2, group 1-3 and group 2-3 between both 30th minute and 24th hour values (p<0.01). Conclusion: In rats with bilateral unstable pelvic fractures due to blunt pelvis trauma, early administration of TRA after trauma significantly reduced the first 24-hour decrease in Hb value. Our study supports the early and prehospital use of TRA in traumas that are predicted to progress with acute bleeding, such as unstable pelvic fractures.

New and Off-Label Uses of Tranexamic Acid.

New and Off-Label Uses of Tranexamic Acid.

The Effect of Tranexamic Acid on Blood Loss and Maternal Outcome in the Treatment of Persistent Postpartum Hemorrhage: A Nationwide Retrospective Cohort Study

Background: Recent results show a protective effect of tranexamic acid on death due to bleeding in patients with postpartum hemorrhage in low- and middle-resource countries. We set out toquantify the association between early administration of tranexamic acid compared to late or no administration and severe acute maternal morbidity and blood loss among women suffering from persistent severe postpartum hemorrhage in a high-income country.Methods and Findings: We performed a nationwide retrospective cohort study in 61 hospitals in the Netherlands.The study population consisted of 1260 women with persistent postpartum hemorrhage who had received at least four units of red cells, or fresh frozen plasma or platelets in addition to red cells. A review of medical records was performed and cross-referenced with blood bank data. The composite endpoint comprised maternal morbidity (hysterectomy, ligation of the uterine arteries, emergency B-Lynch suture, arterial embolization or admission into an intensive care unit) and mortality.Results: 247 women received early tranexamic acid treatment. After adjustment for confounding, odds ratio for the composite endpoint for early tranexamic acid (n= 247) versus no/late tranexamic acid (n= 984) was 0.92 (95% confidence interval (CI) 0.66 to 1.27). Propensity matched analysis confirmed the absence of a difference between women with and without tranexamic acid. Blood loss after administration of first line therapy did not differ significantly between the two groups (adjusted difference -177 mL, CI -509.4 to +155.0).Conclusions: Our findings suggest that in a high-resource country the effect of tranexamic acid on both blood loss and the combined endpoint of maternal mortality and morbidity may be disappointing.Keywords: postpartum hemorrhage, treatment, tranexamic acid, severe acute maternal morbidity, maternal mortality, blood transfusion DisclosuresNo relevant conflicts of interest to declare.

P.26 Routine use of tranexamic acid during elective caesarean section: A district general’s experience

Introduction: The use of tranexamic acid (TXA) to help reduce bleeding or blood transfusions is widely acknowledged, with NICE [1] NICE guideline Blood Transfusion 2015, https://www.nice.org.uk/guidance/ng24 Google Scholar recommending that TXA is offered to all adult patients undergoing surgery, where moderate blood loss is expected. In addition the WOMAN [2] Woman trial collaborators. Effect of early tranexamic acid administration on mortality,hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international randomised, double-blind, placebo-controlled trial. Lancet 2017;389:2105-16 Google Scholar trial also supports its use within the obstetric population, for patients with postpartum haemorrhage. As part of development of our enhanced recovery protocol for elective caesarean patients, we decided to introduce routine administration of TXA, 1g intravenous dose at cord clamping, for all eligible patients, from 1 January 2018.