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Use of Tranexamic Acid in Bleeding Control of Transabdominal and Transvaginal Hysterectomy
Bahadori A, Hirmanpour A, Bahadoran E
Advanced biomedical research. 2022;11:65
Abstract
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.
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Tranexamic acid dose-response relationship for antifibrinolysis in postpartum haemorrhage during Caesarean delivery: TRACES, a double-blind, placebo-controlled, multicentre, dose-ranging biomarker study
Ducloy-Bouthors AS, Gilliot S, Kyheng M, Faraoni D, Turbelin A, Keita-Meyer H, Rigouzzo A, Moyanotidou G, Constant B, Broisin F, et al
British journal of anaesthesia. 2022
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Editor's Choice
Abstract
BACKGROUND The optimal dose of tranexamic acid to inhibit hyperfibrinolysis in postpartum haemorrhage is unclear. Tranexamic Acid to Reduce Blood Loss in Hemorrhagic Cesarean Delivery (TRACES) was a double-blind, placebo-controlled, randomised, multicentre dose-ranging study to determine the dose-effect relationship for two regimens of intravenous tranexamic acid vs placebo. METHODS Women experiencing postpartum haemorrhage during Caesarean delivery were randomised to receive placebo (n=60), tranexamic acid 0.5 g (n=57), or tranexamic acid 1 g i.v. (n=58). Biomarkers of fibrinolytic activation were assayed at five time points, with inhibition of hyperfibrinolysis defined as reductions in the increase over baseline in D-dimer and plasmin-antiplasmin levels and in the plasmin peak time. RESULTS In the placebo group, hyperfibrinolysis was evidenced by a mean increase over baseline [95% confidence interval] of 93% [68-118] for D-dimer level at 120 min and 56% [25-87] for the plasmin-antiplasmin level at 30 min. A dose of tranexamic acid 1 g was associated with smaller increases over baseline (D-dimers: 38% [13-63] [P=0.003 vs placebo]; plasmin-antiplasmin: -2% [-32 to 28] [P=0.009 vs placebo]). A dose of tranexamic acid 0.5 g was less potent, with non-significant reductions (D-dimers: 58% [32-84] [P=0.06 vs placebo]; plasmin-antiplasmin: 13% [18-43] [P=0.051]). Although both tranexamic acid doses reduced the plasmin peak, reduction in plasmin peak time was significant only for the 1 g dose of tranexamic acid. CONCLUSIONS Fibrinolytic activation was significantly inhibited by a dose of intravenous tranexamic acid 1 g but not 0.5 g. Pharmacokinetic-pharmacodynamic modelling of these data might identify the best pharmacodynamic monitoring criteria and the optimal tranexamic acid dosing regimen for treatment of postpartum haemorrhage. CLINICAL TRIAL REGISTRATION NCT02797119.
PICO Summary
Population
Women experiencing postpartum haemorrhage during Caesarean delivery enrolled in the Tranexamic Acid to Reduce Blood Loss in Hemorrhagic Cesarean Delivery (TRACES) trial (n= 175).
Intervention
1g dose of intravenous tranexamic acid (n= 58). 0.5g dose of intravenous tranexamic acid (n= 57).
Comparison
Placebo (n= 60).
Outcome
In the placebo group, hyperfibrinolysis was evidenced by a mean increase over baseline [95% confidence interval] of 93% [68-118] for D-dimer level at 120 min and 56% [25-87] for the plasmin-antiplasmin level at 30 min. Compared to placebo, a dose of tranexamic acid 1g was associated with smaller increases over baseline (D-dimers: 38% [13-63]; plasmin-antiplasmin: -2% [-32 to 28]). A dose of tranexamic acid 0.5g was less potent, with non-significant reductions (D-dimers: 58% [32-84] compared to placebo]; plasmin-antiplasmin: 13% [18-43]). Although both tranexamic acid doses reduced the plasmin peak, reduction in plasmin peak time was significant only for the 1g dose of tranexamic acid.
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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
Abstract
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.
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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
Abstract
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.
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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)
Abstract
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.
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Tranexamic Acid for Prevention of Hemorrhage in Elective Repeat Cesarean Delivery - A Randomized Study
Ogunkua OT, Duryea EL, Nelson DB, Eddins MM, Klucsarits SE, McIntire DD, Leveno KJ
American journal of obstetrics & gynecology MFM. 2022;:100573
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Editor's Choice
Abstract
BACKGROUND The American College of Obstetricians and Gynecologists states that data is insufficient to recommend Tranexamic acid (TXA) prophylaxis for postpartum hemorrhage. OBJECTIVE This study's objective was to evaluate if prophylactic TXA reduces calculated blood loss versus placebo in women undergoing elective repeat cesarean delivery. STUDY DESIGN A double-blind, randomized, placebo-controlled trial, examining calculated blood loss with prophylactic doses of 1-gram of TXA given before skin incision and after placental delivery and standard uterotonics in women with singleton pregnancies at least 37 weeks' gestation, presenting for their second or third cesarean delivery under neuraxial anesthesia. The primary outcome was calculated blood loss at 24 hours. The calculation was based on the participant's height, weight, and the difference in hematocrit before the start of surgery and 24 hours after delivery. Prespecified secondary outcomes were quantification of maternal coagulation activity during the perioperative course. A sample size of 50 women per group was planned (N=100), based on a meta-analysis of mean reduction in blood loss after TXA. RESULTS 723 women were screened, and 110 women were randomized as follows: 55 to TXA and 55 to placebo. The primary outcome of mean calculated blood for TXA (2274 ± 469 mL) and the placebo group (2407 ± 388 mL), p > 0.05. In the secondary outcomes, D-dimer levels were lower in the TXA group than the placebo group 24 hours after delivery (2.1 ± 1.2 µg/mL versus 4.3 ± 2.4 µg/mL), p < 0.001. CONCLUSIONS Prophylactic tranexamic acid did not decrease mean calculated blood loss. Significantly less participants had calculated blood loss greater than 2000 mL in the tranexamic acid group compared to the placebo group with lower levels of D-dimer at 24 hours.
PICO Summary
Population
Women undergoing elective repeat caesarean delivery (n= 110).
Intervention
Prophylactic doses of tranexamic acid (TXA) before skin incision and after placental delivery (n= 55).
Comparison
Standard uterotonics (n= 55).
Outcome
The mean calculated blood loss for TXA was 2,274 ± 469 mL, and for standard uterotonics was 2407 ± 388 mL. D-dimer levels were lower in the TXA group than the placebo group 24 hours after delivery (2.1 ± 1.2 µg/mL vs. 4.3 ± 2.4 µg/mL).
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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
Abstract
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.
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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
Pharmaceutics. 2022;14(3)
Abstract
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.
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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
Abstract
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.
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Hemostatic Effects of Tranexamic Acid in Cesarean Delivery: An Ancillary Study of the TRAAP2 Study
Roullet S, Rivoire T, Houssin C, Labrouche S, Paquin S, Nouette-Gaulain K, Deneux-Tharaux C, Amiral J, James C, Sentilhes L
Thrombosis and haemostasis. 2022
Abstract
BACKGROUND Fibrinolysis activation during delivery contributes to postpartum hemorrhage (PPH). Clot lysis time studied with the global fibrinolytic capacity device (GFC/LT) is a functional test which rapidly assesses fibrinolytic profile. Tranexamic acid (TXA) is an efficient antifibrinolytic therapy. METHODS We prospectively studied fibrinolysis and coagulation in 33 women included in the TRAAP2 trial, which aimed to assess the impact of TXA in preventing PPH following a cesarean delivery. TXA or placebo was randomly administered after childbirth as part of the TRAAP2 trial's protocol. Fibrinolytic (GFC/LT, plasma concentration of fibrinolysis activators and inhibitors) and hemostatic parameters were assayed at three sample times (TREF [T-reference] after anesthesia, T15 and T120minutes after TXA, or placebo administration). RESULTS All cesarean deliveries were elective. In the placebo group, the clot lysis time assessed with GFC/LT significantly decreased between TREF and T120, indicating an activated fibrinolysis (44 [interquartile range, IQR: 40-48] vs. 34 [IQR: 30-36] minutes, p<0.001). In both TXA and placebo groups, significant fluctuations of the plasmatic concentrations of fibrinolytic mediators were noticed over time, suggesting fibrinolysis activation. Clot lysis time measured by GFC/LT was significantly increased in women of the TXA group as compared with those in the placebo group at T15 (120 [120-120] vs. 36 [34-41] minutes, p<0.001) and T120minutes (113 [99-120] vs. 34 [30-36] minutes, p<0.001) after drug administration, indicating a decreased in fibrinolysis in those women. CONCLUSIONS GFC/LT evidenced fibrinolysis activation during cesarean delivery, linked to a decrease in fibrinolytic inhibitors. GFC/LT revealed a significant antifibrinolytic effect of TXA compared with placebo.
