Tranexamic Acid to Prevent Obstetrical Hemorrhage after Cesarean Delivery
Pacheco LD, Clifton RG, Saade GR, Weiner SJ, Parry S, Thorp JM Jr, Longo M, Salazar A, Dalton W, Tita ATN, et al
The New England journal of medicine. 2023;388(15):1365-1375
BACKGROUND Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear. METHODS We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed. RESULTS A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; Pâ€‰=â€‰0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was -1.8 g per deciliter and -1.9 g per deciliter, respectively (mean difference, -0.1 g per deciliter; 95% CI, -0.2 to -0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups. CONCLUSIONS Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.).
Patients undergoing caesarean delivery at 31 U.S. hospitals (n= 11,000).
Tranexamic acid (n= 5,529).
Placebo (n= 5,471).
The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days postpartum, whichever came first. A primary-outcome event occurred in 201 of 5,525 participants (3.6%) in the tranexamic acid group and in 233 of 5,470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% CI [0.74, 1.07]). Estimated intraoperative blood loss of more than 1 litre occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI [0.79, 1.05]). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI [0.82, 0.97]); the change in the haemoglobin level was -1.8 g per decilitre and -1.9 g per decilitre, respectively (mean difference, -0.1 g per decilitre; 95% CI [-0.2, -0.1]); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI [1.02, 1.61]). The frequencies of thromboembolic events and other adverse events were similar in the two groups.
Tranexamic Acid for the Prevention of Blood Loss after Cesarean Among Women With Twins. A Secondary Analysis of the TRAAP2 Randomized Clinical Trial
Sentilhes L, Madar H, Le Lous M, Sénat MV, Winer N, Rozenberg P, Kayem G, Verspyck E, Fuchs F, Azria E, et al
American journal of obstetrics and gynecology. 2022
BACKGROUND Although prophylactic tranexamic acid administration at cesarean delivery resulted in a lower incidence of calculated estimated blood loss > 1000 mL or red-cell transfusion by day 2, its failure to reduce the incidence of hemorrhage-related secondary clinical outcomes (TRAAP2 trial) makes its use questionable. The magnitude of its effect may differ in women at higher risk of blood loss, including those with multiple pregnancies. OBJECTIVE To compare the effect of tranexamic acid vs placebo to prevent blood loss at cesarean delivery among women with multiple pregnancies. STUDY DESIGN Secondary analysis of the TRAAP2 trial data including 319 women with multiple pregnancies in this double-blind, randomized controlled trial from March 2018 through January 2020 in 27 French maternity hospitals. Women with a cesarean before or during labor at 34 or more gestational weeks were randomized to receive intravenously 1 g of tranexamic acid (n=160) or placebo (n=159), both with prophylactic uterotonics. The primary outcome was a calculated estimated blood loss > 1000 mL or a red blood cell transfusion by 2 days after delivery. Secondary outcomes included clinical and laboratory blood loss measurements. RESULTS Of the 4551 women randomized in this trial, 319 had a multiple pregnancy and cesarean delivery, 298 (93.4%) with primary outcome data available. This outcome occurred in 62 of 147 women (42.2%) in the tranexamic acid group and 67 of 152 (44.1%) receiving placebo (adjusted risk ratio, 0.97; 95% CI 0.68-1.38; P=.86). No significant between-group differences occurred for any hemorrhage-related clinical outcomes: gravimetrically estimated blood loss, provider-assessed clinically significant hemorrhage, additional uterotonics, postpartum blood transfusion, arterial embolization, and emergency surgery (P>.05 for all comparisons). CONCLUSION Among women with a multiple pregnancy and cesarean delivery, prophylactic tranexamic acid did not reduce the incidence of any blood loss-related outcomes.
Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean Delivery
Gilliot S, Ducloy-Bouthors AS, Loingeville F, Hennart B, Allorge D, Lebuffe G, Odou P
The aim of this study was to evaluate the population pharmacokinetics of tranexamic acid (TXA) administered intravenously at a single dose of 0.5 or 1 g in parturients undergoing active hemorrhagic cesarean delivery and to evaluate the influence of patient variables on TXA pharmacokinetics. Subjects from three recruiting centers were included in this PK sub-study if randomized in the experimental group (i.v TXA 0.5 g or 1 g over one minute) of the TRACES study. Blood samples and two urinary samples were collected within 6 h after TXA injection. Parametric non-linear mixed-effect modeling (Monolix v2020R1) was computed. The final covariate model building used 315 blood and 117 urinary concentrations from seventy-nine patients. A two-compartment model with a double first-order elimination from the central compartment best described the data. The population estimates of clearance (CL), central volume of distribution (V1), and half-life for a typical 70 kg patient with an estimated renal clearance of 150 mL/min (Cockroft-Gault) were 0.14 L/h, 9.25 L, and 1.8 h. A correlation between estimated creatinine clearance and CL, body weight before pregnancy, and V1 was found and partly explained the PK variability. The final model was internally validated using a 500-run bootstrap. The first population pharmacokinetic model of TXA in active hemorrhagic caesarean section was successfully developed and internally validated.
Prophylactic tranexamic acid to reduce blood loss and related morbidities during hysterectomy: a systematic review and meta-analysis of randomized controlled trials
Abu-Zaid A, Baradwan S, Badghish E, AlSghan R, Ghazi A, Albouq B, Khadawardi K, AlNaim NF, AlNaim LF, Fodaneel M, et al
Obstetrics & gynecology science. 2022
To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the efficacy and safety of prophylactic tranexamic acid (TXA) versus a control (placebo or no treatment) during hysterectomy for benign conditions. Six databases were screened from inception to January 23, 2022. Eligible studies were assessed for risk of bias. Outcomes were summarized as weighted mean differences and risk ratios with 95% confidence intervals in a random-effects model. Five studies, comprising six arms and 911 patients were included in the study. Two and three studies had an overall unclear and low risk of bias, respectively. Estimated intraoperative blood loss, requirement for postoperative blood transfusion, and requirement for intraoperative topical hemostatic agents were significantly reduced in a prophylactic TXA group when compared with a control group. Moreover, postoperative hemoglobin level was significantly higher in the prophylactic TXA group than in the control group. Conversely, the frequency of self-limiting nausea and vomiting was significantly higher in the prophylactic TXA group than in the control group. There were no significant differences between the groups in terms of surgery duration, hospital stay, and diarrhea rate. All the RCTs reported no incidence of major adverse events in either group, such as mortality, thromboembolic events, visual disturbances, or seizures. There was no publication bias for any outcome, and leave-one-out sensitivity analyses demonstrated stability of the findings. Among patients who underwent hysterectomy for benign conditions, prophylactic TXA appeared largely safe and correlated with substantial reductions in estimated intraoperative blood loss and related morbidities.
Use of Tranexamic Acid in Bleeding Control of Transabdominal and Transvaginal Hysterectomy
Bahadori A, Hirmanpour A, Bahadoran E
Advanced biomedical research. 2022;11:65
BACKGROUND Hysterectomy is one of the most common gynecology surgeries. This study aimed to compare perioperative bleeding in transabdominal and transvaginal hysterectomy. MATERIALS AND METHODS This prospective, double-blind, randomized, controlled clinical trial was performed on 80 patients undergoing hysterectomy referred to Shahid Beheshti Hospital, Isfahan, Iran. Patients were divided into two groups of 40; the first group (T) received 1 g intravenous tranexamic acid (TXA) for 20 min preoperatively. The second group (S) received 10 cc normal saline as placebo. Blood samples were taken before and 12 h after surgery for assessment of hemoglobin, hematocrit, and platelet count, the prothrombin time, activated partial thromboplastin time, and serum creatinine as well as volume of blood transfusion. RESULTS There were no significant differences between the two groups in heart rate, diastolic blood pressure (BP), systolic BP, and mean arterial pressure before, during, and after surgery (P > 0.05). There was no significant difference in blood variables before and after surgery (P > 0.05) except the platelet count that was in the normal range in both groups after surgery (P = 0.022). The mean volume of blood transfused in the case group was significantly lower than the control group during surgery (P = 0.008) and 12 h after surgery (P = 0.01). CONCLUSION The prophylactic administration of TXA results in a significant reduction in need for blood transfusion and the duration of surgery. Given the lower risks of using TXA compared to the other drugs, it is recommended in hysterectomy to control bleeding.
The Effect of Intravenous Tranexamic Acid on Myomectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Kathopoulis N, Prodromidou A, Zacharakis D, Chatzipapas I, Diakosavvas M, Kypriotis K, Grigoriadis T, Protopapas A
Journal of personalized medicine. 2022;12(9)
Myomectomy is the preferred surgical treatment for symptomatic women with uterine myomas who wish to preserve their fertility. The procedure may be associated with significant intraoperative blood loss, which predisposes to increased transfusion rates and morbidity. The objective of our systematic review and meta-analysis is to investigate whether intravenous (IV) use of tranexamic acid (TXA) may reduce blood loss during myomectomy. Three electronic databases were screened until June 2022. The eligible studies were assessed for risk of bias. Four randomized controlled trials that reported outcomes from a total of 310 women were finally included in the meta-analysis-155 patients received intravenous TXA while the remaining 155 received placebo injection with normal saline or water for injection. Total estimated blood loss was significantly lower in patients who received TXA before myomectomy compared to control (230 patients MD -227.09 mL 95% CI -426.26, -27.91, p = 0.03). This difference in favor of TXA group remained when intraoperative and postoperative blood loss was separately analyzed. Postoperative hematocrit values and hemoglobin levels did not differ among the two groups (180 patients MD 0.67% 95% CI -0.26, 1.59, p = 0.16 and 250 patients MD 0.17 mg/dL 95% CI 0.07, 0.41, p = 0.17, respectively). The number of patients that received blood transfusion was also not different (310 patients OR 0.46 95% CI -0.14, 1.49, p = 0.19). Total operative time was significantly prolonged in control group compared to TXA (310 patients MD -16.39 min 95% CI -31.44, -1.34 p = 0.03). Our data show that the IV use of TXA may significantly reduce intraoperative blood loss in patients undergoing myomectomy and contribute to reduced operative time.
Safety and efficacy of preoperative tranexamic acid in reducing intraoperative and postoperative blood loss in high-risk women undergoing cesarean delivery: a randomized controlled trial
Shalaby, M. A., Maged, A. M., Al-Asmar, A., El Mahy, M., Al-Mohamady, M., Rund, N. M. A.
BMC pregnancy and childbirth. 2022;22(1):201
BACKGROUND Objective to assess the value of preoperative tranexamic acid (TXA) in reduction of intraoperative and postoperative blood loss in high-risk cesarean delivery (CD). METHODS A double blind randomized controlled trial included 160 high risk women who underwent elective lower segment CD. They were equally randomized to receive either 1 g of TXA or placebo 15 min before surgery. The primary outcome was Intraoperative blood loss. RESULTS The estimated blood loss was significantly higher in the placebo group when compared to TXA group (896.81 ± 519.6 vs. 583.23 ± 379.62 ml, P < 0.001). Both postoperative hemoglobin and hematocrit were lower (9.2 ± 1.6 and 27.4 ± 4.1 vs. 10.1 ± 1.2 and 30.1 ± 3.4, P values < 0.001and 0.012 respectively) and their change percentages (15.41 vs. 7.11%, P < 0.001) were higher in the placebo group when compared to TXA one. The need for further ecbolics was higher in placebo group when compared to TXA group (46.25 vs. 13.75%, P < 0.001). CONCLUSION Preoperative TXA is safe and effective in reducing blood loss during and after high-risk CD. TRIAL REGISTRATION ClincalTrial.gov ID: NCT03820206 .
Topical vs. intravenous administration of tranexamic acid to minimize blood loss in abdominal hysterectomy perioperatively: A randomized controlled study
Mitra S, Jain K, Singh J, Jindal S, Mehra R, Singh S
Journal of anaesthesiology, clinical pharmacology. 2022;38(2):233-239
BACKGROUND AND AIMS Topical application of tranexamic acid (TXA) to bleeding wound surfaces is rapidly gaining recognition and currently a topic of further research in patients undergoing abdominal hysterectomy. The aim of the study was to compare the efficacy of topical vs. intravenous (i.v.) administration of TXA in reducing perioperative blood loss in patients undergoing abdominal hysterectomy. MATERIAL AND METHODS A double-blinded parallel-group randomized controlled study was conducted in a tertiary teaching institute. Group 1 (n = 25) received 10 mg.kg(-1) i.v. bolus of TXA after induction followed by infusion of 1 mg.kg(-1).h(-1) of TXA, in 50 ml of normal saline (NS), till the completion of surgery and just before closure of peritoneum 100 ml of NS was applied topically over the raw surface. Group 2 (n = 25) received 50 ml of NS over 10 min after induction, followed by infusion of 50 ml of NS, till the completion of surgery and just before closure of peritoneum, 1.5 g of TXA mixed in 100 ml of NS was applied topically over the raw surface. The primary outcome was total perioperative blood loss (intraoperative plus 24 h postoperative). The secondary outcomes included change in hemoglobin concentration postoperatively at 12 h, 24 h; need for blood/blood product transfusion; amount of blood/blood product transfused and side effects of TXA. RESULTS Total perioperative blood loss was 312 ± 106.65 ml in group 1 and 325 ± 89.90 ml in group 2 (p = 0.659). It was found that the mean reduction in hemoglobin was 0.7 g.dl(-1) and 0.54 g.dl(-1) in group 1 and 0.67 g.dl(-1) and 0.44 g.dl(-1) in group 2 at 12 h and 24 h respectively, with no significant intergroup difference. CONCLUSION Administration of TXA topically is as efficacious as TXA administered i.v. to minimize perioperative blood loss in patients undergoing abdominal hysterectomy.
Intravenous Tranexamic acid versus placebo during Caesarian section: A comparative study
Iqbal MJ, Mazhar A, Shabir A
Pakistan journal of medical sciences. 2022;38(5):1183-1187
OBJECTIVES To evaluate the effectiveness of Tranexamic Acid in preventing postpartum hemorrhage against placebo in high-risk women undergoing cesarean section. METHODS A double-blinded placebo-controlled comparative trial was conducted at the Obstetrics and Gynecology Department of Nishtar Hospital for one year, from 15(th) June 2020 to 15(th) June 2021. A total of 60 women who were at high risk of postpartum hemorrhage and had to undergo elective cesarean sections were included in the study. Among them, initial 30 patients were administered Tranexamic Acid before skin incision whereas later 30 were treated as the placebo group. These women were then observed for blood loss during surgery and within 24 hrs. after surgery and any postoperative complications such as thromboembolic events, the need for additional uterotonic agents, and blood transfusions. RESULTS Out of 60 women, 30 were placed in each group. The groups had no significant difference in terms of baseline data and post-partum hemorrhage-associated risk factors (p>0.05). However, the occurrence rate of primary post-partum hemorrhage (blood loss greater than 1000 ml) was significantly less in a tranexamic acid group than the placebo group (16.6% vs 60%, respectively, p<0.01). Similarly, the requirement of additional uterotonic agents (13.3% vs 43.3%, respectively) and the need for blood transfusion (6.0% vs 23.3%, respectively) was lower in a tranexamic group than in the placebo group. CONCLUSION The study highlighted the significance of tranexamic acid in controlling post-partum hemorrhages, the requirement of additional uterotonic agents, improving post-partum hemoglobin, and the need for blood transfusion.
Prophylactic tranexamic acid during myomectomy: A systematic review and meta-analysis of randomized controlled trials
Baradwan S, Hafidh B, Latifah HM, Gari A, Sabban H, Abduljabbar HH, Tawfiq A, Hakeem GF, Alkaff A, AlSghan R, et al
European journal of obstetrics, gynecology, and reproductive biology. 2022;276:82-91
OBJECTIVE To conduct a systematic review and meta-analysis of randomized controlled trials on the clinical efficacy and safety of prophylactic tranexamic acid (TXA) versus control (normal saline/no treatment) during myomectomy. METHODS Six databases were screened from inception until 21-February-2022. The eligible studies were assessed for risk of bias. The outcomes were summarized as mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) in a random-effects model. RESULTS Seven studies, comprising eight arms and 571 patients (TXA = 304 patients, control = 267 patients) were analyzed. The included studies had an overall low risk of bias. The mean intraoperative blood loss (MD = -224.34 ml, 95% CI [-303.06, -145.61], p < 0.001), mean postoperative blood loss, and mean total blood loss were significantly reduced in favor of the prophylactic TXA group. Additionally, the mean postoperative hemoglobin (MD = 0.4 mg/dl, 95% CI [0.11, 0.68], p = 0.006) and mean postoperative hematocrit levels were significantly higher in favor of the prophylactic TXA group. While the mean hospital stay was significantly reduced in favor of the prophylactic TXA group (MD = -0.39 d, 95% [-0.74, -0.04], p = 0.03), there was no significant difference between both groups regarding the mean operation time and rate of blood transfusion. None of the participants in both groups developed any incidence of thromboembolic events. The rate of nausea was significantly higher in disfavor of the prophylactic TXA group (RR = 2.68, 95% CI [1.11, 6.43], p = 0.03). CONCLUSION Among patients undergoing myomectomy, prophylactic TXA was largely safe and linked to substantial reductions in perioperative blood loss and related morbidities.