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The effects of tranexamic acid on platelets in patients undergoing cardiac surgery: a systematic review and meta-analysis
Zou, Z. Y., He, L. X., Yao, Y. T.
Journal of thrombosis and thrombolysis. 2023
Abstract
This meta-analysis was designed to evaluate the effects of tranexamic acid (TXA) on platelets in patients undergoing cardiac surgery (CS). Relevant trials were identified by computerized searches of PUBMED, Cochrane Library, EMBASE, OVID, China National Knowledge Infrastructure (CNKI), Wanfang Data and VIP Data till Jun 4th, 2022, were searched using search terms "platelet", "Tranexamic acid", "cardiac surgery", "randomized controlled trial" database search was updated on Jan 1st 2023. Primary outcomes included platelet counts, function and platelet membrane proteins. Secondary outcome included postoperative bleeding. Search yielded 49 eligible trials, which were finally included in the current study. As compared to Control, TXA did not influence post-operative platelet counts in adult patients undergoing on- or off-pump CS, but significantly increased post-operative platelet counts in pediatric patients undergoing on-pump CS [(WMD = 16.72; 95% CI 6.33 to 27.10; P = 0.002)], significantly increased post-operative platelet counts in adults valvular surgery [(WMD = 14.24; 95% CI 1.36 to 27.12; P = 0.03). Additionally, TXA improved ADP-stimulated platelet aggression [(WMD = 1.88; 95% CI 0.93 to 2.83; P = 0.0001)] and improved CD63 expression on platelets [(WMD = 0.72; 95% CI 0.29 to 1.15; P = 0.001)]. The current study demonstrated that TXA administration did not affect post-operative platelet counts in adult patients undergoing either on- or off-pump CABG, but significantly increased post-operative platelet counts in pediatric patients undergoing on-pump CS and adults valvular surgery. Furthermore, TXA improved ADP-stimulated platelet aggression and improved CD63 expression on platelets. To further confirm this, more well designed and adequately powered randomized trials are needed.
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The efficacy and safety of intravenous administration of tranexamic acid in patients undergoing cardiac surgery: Evidence from a single cardiovascular center
Lin, P. S., Yao, Y. T., Tian, L. J., Jiang, J. J., Zhang, Y., He, L. X., Yu, Y. P., Ma, J.
Medicine. 2023;102(20):e33819
Abstract
BACKGROUND The current study was performed to systemically review the efficacy and safety of tranexamic acid (TXA) in patients undergoing cardiac surgery at a single large-volume cardiovascular center. METHODS A computerized search of electronic databases was performed to identify all relevant studies using search terms till December 31st, 2021. The primary outcomes were postoperative blood loss and the composite incidence of mortality and morbidities during hospitalization. Secondary outcomes included postoperative massive bleeding and transfusion, postoperative recovery profiles, coagulation functions, inflammatory variables, and biomarkers of vital organ injury. RESULTS Database search yielded 23 qualified studies including 27,729 patients in total. Among them, 14,136 were allocated into TXA group and 13,593 into Control group. The current study indicated that intravenous TXA significantly reduced total volume of postoperative bleeding in both adult and pediatric patients, and that medium- and high-dose TXA were more effective than low-dose TXA in adult patients (P < .05). The current study also demonstrated that intravenous TXA, as compared to Control, remarkably reduced postoperative transfusion incidences and volume of red blood cell and fresh frozen plasma, and reduced postoperative transfusion incidence of platelet concentrates (PC) (P < .05) without obvious dose-effects (P > .05), but TXA did not reduce PC transfusion volume postoperatively in adult patients (P > .05). For pediatrics, TXA did not significantly reduce postoperative transfusion incidence and volume of allogenic red blood cell, fresh frozen plasma and PC (P > .05). Additionally, the current study demonstrated that intravenous TXA did not influence the composite incidence of postoperative mortality and morbidities in either adults or pediatrics during hospitalization (P > .05), and that there was no obvious dose-effect of TXA in adult patients (P > .05). CONCLUSIONS This current study suggested that intravenous TXA significantly reduced total volume of postoperative bleeding in both adult and pediatric patients undergoing cardiac surgery at the single cardiovascular center without increasing the composite incidence of mortality and morbidities.
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Prophylactic Use of Antifibrinolytics During Pediatric Cardiac Surgery With Cardiopulmonary Bypass on Postoperative Bleeding and Transfusion: A Systematic Review and Meta-Analysis
Schertz K, Karam O, Demetres M, Faraoni S, Faraoni D, Nellis ME
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2022
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Editor's Choice
Abstract
OBJECTIVES To determine the effect of intraoperative antifibrinolytics, including tranexamic acid (TXA), aminocaproic acid (EACA), or aprotinin, on bleeding in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). DATA SOURCES Relevant articles were systematically searched from Ovid MEDLINE, Ovid EMBASE, CINAHL, Cochrane Library, and Web of Science to November 15, 2021. STUDY SELECTION Abstracts were screened, and full texts were reviewed using predetermined inclusion and exclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. DATA EXTRACTION A standardized data extraction tool was used. DATA SYNTHESIS Sixty-eight studies including 28,735 patients were analyzed. TXA compared with placebo resulted in a mean decrease in chest tube output of 9.1 mL/kg (95% CI, 6.0-12.3 mL/kg), I2 equals to 65.2%, p value of less than 0.001, platelet requirement of 2.9 mL/kg (95% CI, 0.1-5.8 mL/kg), I2=72.5%, p value less than 0.001 and plasma requirement of 4.0 mL/kg (95% CI, 0.6-7.2 mL/kg), I2 equals to 94.5%, p value less than0.001. Aprotinin compared with placebo resulted in a mean decrease in chest tube output of 4.3 mL/kg (2.4-6.2 mL/kg), I2 equals to 66.3%, p value of less than 0.001, platelet transfusion of 4.6 mL/kg (95% CI, 0.6-8.6 mL/kg), I2 equals to 93.6%, p value of less than 0.001, and plasma transfusion of 7.7 mL/kg (95% CI, 2.1-13.2 mL/kg), I2 equals to 95.3%, p value of less than 0.001. EACA compared with placebo resulted in a mean decrease in chest tube output of 9.2 mL/kg (2.3-21.0 mL/kg), I2 equals to 96.4%, p value of less than 0.001, RBC transfusion of 7.2 mL/kg (95% CI, 2.4-12.1 mL/kg), I2 equals to 94.5%, p value equals to 0.002, and platelet transfusion of 10.7 mL/kg (95% CI, 2.9-18.5 mL/kg), I2 equals to 0%, p value of less than 0.001. No statistical difference was observed in chest tube output when TXA was compared with aprotinin. Subgroup analysis of cyanotic patients showed a significant decrease in chest tube output, platelet requirement, and plasma requirement for patients receiving aprotinin. Overall, the quality of evidence was moderate. CONCLUSIONS Antifibrinolytics are effective at decreasing blood loss and blood product requirement in children undergoing cardiac surgery with CPB although the quality of evidence is only moderate.
PICO Summary
Population
Children undergoing cardiac surgery with cardiopulmonary bypass, (68 studies, n= 28,735).
Intervention
Intraoperative antifibrinolytics, including tranexamic acid (TXA), aminocaproic acid (EACA), or aprotinin.
Comparison
Placebo.
Outcome
TXA compared with placebo resulted in a mean decrease in chest tube output of 9.1 mL/kg (95% Confidence Interval (CI): 6.0-12.3 mL/kg), platelet requirement of 2.9 mL/kg (95% CI: 0.1-5.8 mL/kg), and plasma requirement of 4.0 mL/kg (95% CI: 0.6-7.2 mL/kg). Aprotinin compared with placebo resulted in a mean decrease in chest tube output of 4.3 mL/kg (2.4-6.2 mL/kg), platelet transfusion of 4.6 mL/kg (95% CI: 0.6-8.6 mL/kg), and plasma transfusion of 7.7 mL/kg (95% CI: 2.1-13.2 mL/kg). EACA compared with placebo resulted in a mean decrease in chest tube output of 9.2 mL/kg (2.3-21.0 mL/kg), red blood cell transfusion of 7.2 mL/kg (95% CI: 2.4-12.1 mL/kg), and platelet transfusion of 10.7 mL/kg (95% CI: 2.9-18.5 mL/kg). Overall, the quality of evidence was moderate.
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Anti-inflammatory effect of tranexamic acid on adult cardiac surgical patients: A PRISMA-compliant systematic review and meta-analysis
Xie CM, Yao YT, He LX, Yang K
Frontiers in surgery. 2022;9:951835
Abstract
OBJECTIVE This study aims to evaluate the anti-inflammatory effect of tranexamic acid (TXA) on adult cardiac surgical patients. METHODS PubMed, Embase, Ovid, Web of Science, CNKI, VIP, and WANFANG databases were systematically searched using the related keywords for cardiac surgical randomized controlled trials (RCTs) published from their inception to February 1, 2022. The primary outcomes were postoperative inflammatory biomarkers levels. The secondary outcomes were postoperative systemic inflammatory response syndrome and other major postoperative outcomes. The odds ratios and/or the weighted mean difference (WMD) with a 95% confidence interval (CI) were used to pool the data. RESULTS Ten RCTs with 770 adult cardiac surgical patients were included. Compared with placebo, TXA achieved statistically significant inhibition of the postoperative interleukin (IL)-6 level (postoperative 6 h: n = 6 trials; WMD -31.66; 95% CI: -45.90, -17.42; p < 0.0001; I (2 )= 93%; postoperative 24 h: n = 8 trials; WMD, -44.06; 95% CI: -69.21, -18.91; p = 0.006; I (2 )= 100%); IL-8 level postoperative 24 h, TNF-α level postoperative 24 h, NE level postoperative 6 h: n = 3 trials; WMD, -36.83; 95% CI: -68.84, -4.83; p = 0.02; I (2 )= 95%); tissue necrosis factor alpha (TNF-α) level (postoperative 6 h: n = 3 trials; WMD, -7.21; 95% CI: -12.41, -2.01; p = 0.007; I (2 )= 47%; postoperative 24 h: n = 5 trials; WMD, -10.02; 95% CI: -14.93, -5.12; p < 0.0001; I (2 )= 94%); and neutrophil elastase (NE) level (postoperative 6 h: n = 3 trials; WMD, -66.93; 95% CI: -111.94, -21.92; p = 0.004; I (2 )= 86%). However, TXA achieved no statistically significant influence on the postoperative 24 h NE level. CONCLUSIONS TXA had a significant anti-inflammatory effect in adult cardiac surgical patients, as evidenced by the reduction of multiple postoperative proinflammatory biomarkers levels, but these results should be interpreted carefully and cautiously, as only a limited number of studies were included and there was high heterogeneity between them. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022312919.
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The effect of tranexamic acid on myocardial injury in cardiac surgical patients: a systematic review and meta-analysis
Wang X, Li L, He L, Yao Y
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2022
Abstract
Tranexamic acid (TXA) is one of the most commonly used antifibrinolytic agents for surgical patients. However, the effect of TXA on myocardial injury remains controversial. We systemically reviewed literature regarding the effectiveness of TXA on myocardial injury in patients who have undergone a cardiac surgery. We included all randomized controlled trials (RCTs) comparing TXA and control (saline) in cardiac surgical patients. Relevant studies were identified by a comprehensive electronic literature search from database inception to 15 August 2021. A standardized data extraction form was used to collect methodological and outcome variables from each eligible study. We conducted a meta-analysis to estimate the pooled effect size of TXA administration on myocardial injury. In total, eight RCTs were identified, with 292 patients in the TXA group, and 241 patients in saline or control group. The meta-analysis demonstrated that patients in the TXA group had lower levels of CK-MB and cTnI within 24 h postoperatively (CK-MB: P = 0.005; cTnI: P = 0.01), compared with the saline group. No significant difference was found with respect to AST level (P = 0.71) between TXA and saline groups within 24 h postoperatively. TXA administration was found to be associated with less myocardial injury among patients who have undergone cardiac surgery. High-quality randomized controlled trials are warranted to further examine the cardioprotective effects of TXA.
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Tranexamic acid reduces postoperative blood loss in Chinese pediatric patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis
Zou ZY, He LX, Yao YT
Medicine. 2022;101(9):e28966
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Abstract
BACKGROUND Tranexamic acid has been increasingly used for blood conservation in cardiac surgery. However, the evidence supporting the routine use of tranexamic acid in Chinese pediatric patients undergoing cardiac surgery remains weak. This meta-analysis aimed to systematically review the efficacy of tranexamic acid when applying to Chinese pediatric patients undergoing cardiac surgery. PARTICIPANTS Chinese pediatric patients undergoing cardiac surgery. INTERVENTIONS Tranexamic acid or control drugs (saline/blank). METHODS PUBMED, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Data till May 4, 2021, database search was updated on August 1. Primary outcomes of interest included postoperative bleeding, allogeneic transfusion, and reoperation for bleeding. Secondary outcomes of interest included postoperative recovery. For continuous/dichotomous variables, treatment effects were calculated as weighted mean difference (WMD)/odds ratio and 95% confidence interval. RESULTS A database search yielded 15 randomized controlled trials including 1641 patients, where 8 studies were allocated into non-cyanotic congenital group, 5 were allocated into cyanotic congenital group, and the other 2 were allocated into combined cyanotic/non-cyanotic group. This meta-analysis demonstrate that tranexamic acid administration can reduce the postoperative 24 hours blood loss in non-cyanotic, cyanotic, and combined cyanotic/non-cyanotic patients, the red blood cell transfusion in non-cyanotic and cyanotic patients, and the fresh frozen plasma transfusion in non-cyanotic and combined cyanotic/non-cyanotic patients. CONCLUSION This meta-analysis demonstrates that tranexamic acid is highly effective in reducing the blood loss in Chinese pediatric cardiac surgery, but it behaves poorly when it comes to the transfusion requirement. To further confirm this, more well-designed and adequately-powered randomized trials are needed.
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Efficacy and safety of aprotinin in paediatric cardiac surgery: A systematic review and meta-analysis
Atasever AG, Eerens M, Van den Eynde R, Faraoni D, Rex S
European journal of anaesthesiology. 2021
Abstract
BACKGROUND The relicensing of aprotinin in Europe and Canada has stimulated discussions on its usefulness in paediatric cardiac surgery. OBJECTIVE To systematically evaluate the available evidence on the efficacy and safety of aprotinin in paediatric cardiac surgery. DESIGN Systematic review of all randomised and observational studies comparing aprotinin with tranexamic acid, epsilon aminocaproic acid, placebo or no drug in paediatric cardiac surgery. Meta-analyses were performed on efficacy and safety outcomes. DATA SOURCES PubMed, Cochrane Central Register of Controlled Trials, Web of Science and Embase were searched from January 2000 to March 2021. ELIGIBILITY CRITERIA Studies that enrolled children under 18 years undergoing cardiac surgery with cardiopulmonary bypass. RESULTS Thirty-two studies enrolling a total of 63 894 paediatric cardiac procedures were included. Aprotinin significantly reduced total blood loss [mean difference -4.70 ml kg-1, 95% confidence interval (CI), -7.88 to -1.53; P = 0.004], postoperative transfusion requirements and the incidence of surgical re-exploration for bleeding [odds ratio (OR) 0.74, 95% CI, 0.56 to 0.97; P = 0.03]. Aprotinin had no effects on 30-day mortality (OR 1.02, 95% CI, 0.93 to 1.11; P = 0.73) and on other safety outcomes, except for the incidence of renal replacement therapy (RRT), which was significantly increased in patients given aprotinin (OR 1.29, 95% CI, 1.08 to 1.54; P = 0.006). Findings from observational and randomised controlled trials did not largely differ. A sub-group analysis in neonates showed that aprotinin significantly reduced packed red blood cell transfusions and the incidence of postoperative surgical re-exploration for bleeding and/or tamponade. When compared with lysine analogues, aprotinin was more effective at reducing bleeding and transfusion without increasing the risk of side effects. CONCLUSION This meta-analysis suggests that aprotinin is effective and well tolerated in paediatric cardiac surgery. Given the large heterogeneity of the results and the risk of selection bias in observational studies, large randomised controlled trials are warranted.
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Intravenous Tranexamic Acid Decreases Blood Transfusion in Off-Pump Coronary Artery Bypass Surgery: A Meta-analysis
Sun L, An H, Feng Y
The heart surgery forum. 2020;23(1):E039-e049
Abstract
BACKGROUND Tranexamic acid (TXA) has been widely used during on-pump coronary artery bypass graft (CABG) surgery owing to its antifibrinolytic effect. However, the efficacy and safety of TXA in off-pump CABG surgery remains unconfirmed, especially intravenous (IV) administration. OBJECTIVE The aim of this study was to evaluate the effectiveness and safety of IV administration of TXA in off-pump CABG settings. METHODS AND RESULTS A comprehensive literature search was performed to identify randomized controlled trials (RCTs) that compared IV use of TXA with placebo in the reduction of postoperative 24-hour blood transfusion, as well as postoperative death and thrombotic events. The combined estimations were compiled with a fixed-effects model or, if heterogeneity existed, a random-effects model. Funnel plots and Egger's test were used to assess potential publication bias. Subgroup analyses were used to explore possible sources of heterogeneity. In total, 12 RCTs met the inclusion criteria. IV administration of TXA significantly reduced the risk of packed red blood cell (PRBC) transfusion [risk ratio (RR) = 0.61, 95% confidence interval (CI) 0.503 to 0.756, P < .001, I2 = 0.0%) during the 24 hours after surgery. However, there was no statistical significance in platelet (RR = 0.613, 95% CI 0.112 to 3.348, P = .572, I2 = 0.0%) or total fresh frozen plasma (FFP) (RR = 0.511, 95% CI 0.246 to 1.063, P = .073, I2 = 0.0%) transfusion. Also, no significant difference was found in major adverse events (death or thrombotic complications) (RR = 0.917, 95% CI 0.532 to 1.581, P = .756, I2 = 0.0%) between the 2 groups. Interestingly, further subgroup analysis demonstrated that IV TXA decreased the risk of prothrombin time (PT)- and international normalized ratio (INR)-guided FFP transfusion (RR = 0.462, 95% CI 0.296 to 0.721, P = .001, I2 = 0.0%). CONCLUSION IV TXA was effective in reducing allogeneic blood component transfusion (PRBCs and PT- or INR-guided FFP transfusion), without increasing the incidence of postoperative death or thrombotic complications in off-pump CAB surgery.
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The effect of tranexamic acid on the values of activated clotting time in patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis
Yao, Y. T., He, L. X., Tan, J. C.
Journal of Clinical Anesthesia. 2020;67:110020
Abstract
STUDY OBJECTIVE Activated clotting time (ACT) is a non-specific test to evaluate the adequacy of systemic heparinization whose value could be influenced by many factors. Tranexamic acid (TXA) is a widely used antifibrinolytic agent worldwide and whether TXA influences ACT value in cardiac surgical patients remains unknown. Current study was performed to address this question. DESIGN Systematic review and meta-analysis. PUBMED, Cochrane Library, EMBASE, OVID and Chinese BioMedical Literature & Retrieval System were searched using search terms "tranexamic acid", "activated clotting time", "cardiac surgery", "randomized controlled trial" till May 7th, 2020, to identify all relevant randomized controlled trials (RCTs). SETTING Operating room. PATIENTS Cardiac surgical patients. INTERVENTIONS TXA or placebo. MEASUREMENTS Primary outcomes of interest included peri-operative ACT values. Secondary outcomes of interest include heparin dosage, protamine dosage, postoperative bleeding and blood transfusion. MAIN RESULTS Search yielded 13 studies including 1168 patients, and 619 patients were allocated into Group TXA and 549 into Group Control (placebo). Meta-analysis suggested that, ACT values after heparinization [(WMD = -1.45; 95%CI: -12.52 to 15.43; P = 0.84)] and after protamine [(WMD = -1.18; 95%CI: -2.81 to 0.46; P = 0.16)] were comparable between Group TXA and Group Control, and that TXA did not influence heparin dose in adult patients [(WMD = 0.38; 95%CI: 0.30 to 0.46; P<0.00001) with no heterogeneity (I(2) = 4%, P = 0.35)] and protamine dose for heparin reversal [(WMD = 5.23; 95%CI: -0.33 to 10.80; P = 0.07) with no heterogeneity (I(2) = 0, P = 0.58)]. Meta-analysis also demonstrated that, TXA administration significantly reduced post-operative bleeding volume [(WMD = -126.33; 95%CI: -177.46 to -75.19; P < 0.0001), post-operative red blood cell (RBC) transfusion volume [(WMD = -71.86; 95% CI: -88.22 to -55.50; P < 0.00001), fresh frozen plasma (FFP) transfusion volume [(WMD = -13.83; 95% CI: -23.67 to -4.00; P = 0.006) and platelet concentrate (PC) transfusion volume [(WMD = -0.20; 95% CI: -0.29 to -0.10; P < 0.0001). CONCLUSION This meta-analysis suggested that, TXA administration did not influence ACT value, heparin and protamine doses, but significantly reduced post-operative blood loss and transfusion requirement in cardiac surgical patients.
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Exposure-Response Relationship of Tranexamic Acid in Cardiac Surgery
Zufferey PJ, Lanoiselée J, Graouch B, Vieille B, Delavenne X, Ollier E
Anesthesiology. 2020
Abstract
BACKGROUND It is unclear whether high-dose regimens of tranexamic acid in cardiac surgery (total dose, 80 to 100 mg/kg) confer a clinical advantage over low-dose regimens (total dose, approximately 20 mg/kg), particularly as tranexamic acid-associated seizure may be dose-related. The authors' aim was to characterize the exposure-response relationship of this drug. METHODS Databases were searched for randomized controlled trials of intravenous tranexamic acid in adult patients undergoing cardiopulmonary bypass surgery. Observational studies were added for seizure assessment. Tranexamic acid concentrations were predicted in each arm of each study using a population pharmacokinetic model. The exposure-response relationship was evaluated by performing a model-based meta-analysis using nonlinear mixed-effect models. RESULTS Sixty-four randomized controlled trials and 18 observational studies (49,817 patients) were included. Seventy-three different regimens of tranexamic acid were identified, with the total dose administered ranging from 5.5 mg/kg to 20 g. The maximum effect of tranexamic acid for postoperative blood loss reduction was 40% (95% credible interval, 34 to 47%), and the EC50 was 5.6 mg/l (95% credible interval, 0.7 to 11 mg/l). Exposure values with low-dose regimens approached the 80% effective concentration, whereas with high-dose regimens, they exceeded the 90% effective concentration. The predicted cumulative blood loss up to 48 h postsurgery differed by 58 ml between the two regimens, and the absolute difference in erythrocyte transfusion rate was 2%. Compared to no tranexamic acid, low-dose and high-dose regimens increased the risk of seizure by 1.2-fold and 2-fold, respectively. However, the absolute risk increase was only clinically meaningful in the context of prolonged open-chamber surgery. CONCLUSIONS In cardiopulmonary bypass surgery, low-dose tranexamic acid seems to be an appropriate regimen for reducing bleeding outcomes. This meta-analysis has to be interpreted with caution because the results are observational and dependent on the lack of bias of the predicted tranexamic acid exposures and the quality of the included studies.