Clinical observation of blood loss reduced by tranexamic acid during and after caesarian section: a multi-center, randomized trial

doi:10.1016/S0301-2115(03)00287-2

European Journal of Obstetrics & Gynecology and Reproductive Biology

Volume 112, Issue 2, 10 February 2004, Pages 154-157

https://doi.org/10.1016/S0301-2115(03)00287-2 Get rights and content

Abstract

Objectives: To explore the efficacy and safety of tranexamic acid at caesarian section (CS). Study design: Prospective, randomized, case-controlled clinical trial. Population: One hundred and eighty primiparas were randomized into two groups. The study group, 91 women, received tranexamic acid immediately before CS whereas the control group, 89 women did not. Method: Blood was collected during two periods. The first period was from placental delivery to the end of CS and the second was from the end of CS to 2 h postpartum. The quantity of blood was measured and compared between the two groups. Complete blood count, urinalysis, liver and renal function, prothrombin time and activity, were tested in the two groups. Results: Tranexamic acid significantly reduced the quantity of blood from the end of CS to 2 h postpartum: 42.75±40.45 ml in the study group versus 73.98±77.09 ml in the control group (P=0.001). It also significantly reduced the quantity of total blood from placental delivery to 2 h postpartum: 351.57±148.20 ml in the study group, 439.36±191.48 ml in the control group (P=0.002). No complications or side effects were reported in either group. Conclusions: Tranexamic acid statistically reduces the extent of bleeding from placental delivery to 2 h postpartum and its use was not associated with any side effects or complications. Thus, tranexamic acid can be used safely and effectively to reduce bleeding resulting from CS.

Introduction

Caesarian section (CS) rates have increased to as high as 40–50% in many areas of China.

Delivery by CS can cause more complications than normal vaginal delivery and one of the most common complications is hemorrhaging, which can be life threatening. In order to reduce maternal mortality and morbidity caused by bleeding, it is important to reduce the extent of bleeding during and after CS.

Tranexamic acid is an inhibitor of fibrinolysis. It has been routinely used for many years to reduce hemorrhaging during and after surgical procedures [1] such as coronary artery bypass, scoliosis surgery, and knee arthroplasty. It has been shown to be very useful for reducing blood loss and blood transfusion, but there has been no report on preventing blood loss at CS. In this study, the efficacy and safety of tranexamic acid was investigated in the management of CS.

Section snippets

Participants and design

A multi-center, prospective, randomized, case-controlled clinical trial was carried out on 180 primiparas in three hospitals. The primiparas were allocated into two groups using a randomized consecutive numbered chart. The same team in each hospital operated on all the women and one person in each hospital collected the data.

Selection criteria

1.
Term primipara with a singleton delivered by CS.
2.
Regular perinatal care.
3.
Adherence to research regulations.
4.
Informed consent obtained.

Exclusion criteria

1.
Severe medical and surgical complications

Patient characteristics

The patients’ characteristics in the two groups were similar, with no statistical difference between the two groups (Table 1). There was also no significant difference in regard to obstetric complications (such as pregnancy-induced hypertension; fetal growth restriction; premature rupture of the membranes; poor obstetrical history) and indications for CS including pregnancy with complications; abnormal presentation; abnormal pelvis; fetal distress; previous CS; older primipara; refusal of

Discussion

Tranexamic acid exerts its antifibrinolytic effect by blocking the lysine-binding locus of the plasminogen and plasmin molecules, thereby preventing the binding of plasminogen and plasmin to the fibrin substrate. Tranexamic acid also inhibits the conversion of plasminogen to plasmin by the plasminogen activators [2]. It has been used in the treatment of bleeding for many years.

During placental delivery, fibrinogen and fibrin are rapidly degraded, whereas plasminogen activators and fibrin

Acknowledgements

We thank Mr. Tsuneo Konno and Dr. Moriaki Akasaki for substantial help with this study.

References (5)

D. Katsaros et al.
Tranexamic acid reduces postbypass blood use: a double-blinded, prospective, randomized study of 210 patients
Ann. Thorac. Surg.
(1996)
M. Hoylaerts et al.
Studies on the mechanism of the antifibrinolytic action of tranexamic acid
Biochim. Biophys. Acta
(1981)

There are more references available in the full text version of this article.

Cited by (156)

Tranexamic acid for the prevention of blood loss after cesarean section: an updated systematic review and meta-analysis of randomized controlled trials
2023, American Journal of Obstetrics and Gynecology MFM
Tranexamic acid is a cost-effective intervention for the prevention of postpartum hemorrhage among women who undergo cesarean delivery, but the evidence to support its use is conflicting. We conducted this meta-analysis to evaluate the efficacy and safety of tranexamic acid in low- and high-risk cesarean deliveries.
We searched MEDLINE (via PubMed), Embase, the Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform portal from inception to April 2022 (updated October 2022 and February 2023) with no language restrictions. In addition, grey literature sources were also explored.
All randomized controlled trials that investigated the prophylactic use of intravenous tranexamic acid in addition to standard uterotonic agents among women who underwent cesarean deliveries in comparison with a placebo, standard treatment, or prostaglandins were included in this meta-analysis.
We used the revised Cochrane Risk of Bias tool (RoB 2.0) to assess the quality of the included randomized controlled trials. RevMan 5.4 was used to conduct all statistical analyses using a random-effects model.
We included 50 randomized controlled trials (6 in only high-risk patients and 2 with prostaglandins as the comparator) that evaluated tranexamic acid in our meta-analysis. Tranexamic acid reduced the risk for blood loss >1000 mL, the mean total blood loss, and the need for blood transfusion in both low- and high-risk patients. Tranexamic acid was associated with a beneficial effect in the secondary outcomes, including a decline in hemoglobin levels and the need for additional uterotonic agents. Tranexamic acid increased the risk for nonthromboembolic adverse events but, based on limited data, did not increase the incidence of thromboembolic events. The administration of tranexamic acid before skin incision, but not after cord clamping, was associated with a large benefit. The quality of evidence was rated as low to very low for outcomes in the low-risk population and moderate for most outcomes in the high-risk subgroup.
Tranexamic acid may reduce the risk for blood loss in cesarean deliveries with a higher benefit observed in high-risk patients, but the lack of high-quality evidence precludes any strong conclusions. The administration of tranexamic acid before skin incision, but not after cord clamping, was associated with a large benefit. Additional studies, especially in the high-risk population and focused on evaluating the timing of tranexamic acid administration, are needed to confirm or refute these findings.
Analysis of the efficacy of prophylactic tranexamic acid in preventing postpartum bleeding: systematic review with meta-analysis of randomized clinical trials
2023, Brazilian Journal of Anesthesiology (English Edition)
Postpartum Hemorrhage (PPH) is one of the main causes of maternal mortality, mainly in the poorest regions of the world, drawing attention to the need for strategies for preventing it. This study aims to evaluate the efficacy of prophylactic administration of Tranexamic Acid (TXA) in decreasing blood loss in pregnant women in delivery, preventing PPH.
Systematic review of randomized clinical trials. We searched for publications in PubMed, EMBASE and Cochrane Library databases, with the uniterms “postpartum, puerperal hemorrhage” and “tranexamic acid”, published between January of 2004 and January of 2020. The eligibility criteria were trials published in English with pregnant women assessed during and after vaginal or cesarean delivery about the effect of prophylactic use of TXA on bleeding volume. The random-effects model was applied with the DerSimonian-Laird test and the Mean Difference (MD) was calculated for continuous variables together with each 95% CI. This systematic review was previously registered in the PROSPERO platform under the registration n° CRD42020187393.
Of the 630 results, 16 trials were selected, including one with two different doses, performing a total of 6731 patients. The intervention group received a TXA dose that varied between 10 mg.kg⁻¹ and 1g (no weight calculation). The TXA use was considered a protective factor for bleeding (MD: -131.07; 95% CI: -170.00 to -92.78; p = 0.000) and hemoglobin variation (MD: -0.417; 95% CI: -0.633 to -0.202; p = 0.000). In the subgroup analysis related to the cesarean pathway, the effect of TXA was even greater.
The prophylactic use of tranexamic acid is effective in reducing the post-partum bleeding volume.
CRD42020187393.
Tranexamic acid for the prevention of postpartum hemorrhage in women undergoing cesarean delivery: an updated meta-analysis
2022, American Journal of Obstetrics and Gynecology
This study aimed to assess the efficacy and safety of prophylactic tranexamic acid administration vs standard uterotonic agents alone among women undergoing cesarean delivery.
MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar were systematically searched from inception to June 30, 2021.
Randomized controlled trials comparing intravenous tranexamic acid administration with placebo in women undergoing cesarean delivery and receiving standard prophylactic uterotonic agents were held eligible.
The risk of bias of individual studies was appraised with the Risk of Bias 2 tool. Meta-analysis was conducted by fitting random-effects models using restricted maximum likelihood. Subgroup analysis was performed on the basis of country, protocol availability, double-blinding, risk of bias, sample size, and tranexamic acid dose. A 1-stage meta-analysis was performed as a sensitivity analysis. The credibility of outcomes was appraised with the Grading of Recommendations Assessment, Development and Evaluation approach.
Overall, 36 studies with 10,659 women were included. Tranexamic acid administration was associated with significantly lower total blood loss (mean difference, −189.44 mL; 95% confidence intervals, −218.63 to −160.25), lower hemoglobin drop (mean difference, 8.22%; 95% confidence interval, 5.54–10.90), decreased risk of blood loss of >1000 mL (odds ratio, 0.37; 95% confidence interval, 0.22–0.60), transfusion requirement (odds ratio, 0.41; 95% confidence interval, 0.26–0.65), and need of additional uterotonics (odds ratio, 0.36; 95% confidence interval, 0.25–0.52). Subgroup analysis indicated a greater effect of tranexamic acid on total blood loss reduction in low-middle income countries. The outcomes remained stable by separately evaluating women at low bleeding risk. The 1-stage meta-analysis demonstrated similar outcomes with the primary analysis. The quality of evidence was judged to be moderate regarding total blood loss and hemoglobin percentage change and low for the other outcomes.
This meta-analysis suggested that prophylactic tranexamic acid administration is effective among women undergoing cesarean delivery in lowering postpartum blood loss and limiting hemoglobin drop. Further research is needed to test its efficacy in high-risk populations and verify its safety profile.
Tranexamic acid for prevention of hemorrhage in elective repeat cesarean delivery—a randomized study
2022, American Journal of Obstetrics and Gynecology MFM
The American College of Obstetricians and Gynecologists states that the current data are insufficient to recommend tranexamic acid prophylaxis for postpartum hemorrhage.
This study's objective was to evaluate if prophylactic tranexamic acid treatment reduces the calculated blood loss when compared with a placebo in women undergoing an elective repeat cesarean delivery.
This was a double-blind, randomized, placebo-controlled trial in which the calculated blood loss was determined after administration of prophylactic doses of 1 g of tranexamic acid before skin incision and after placental delivery and standard uterotonics in women with singleton pregnancies at ≥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 each 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 tranexamic acid.
A total of 723 women were screened, and 110 women were randomized as follows: 55 to the tranexamic acid group and 55 to the placebo group. The primary outcome of mean calculated blood loss was 2274±469 mL for the tranexamic acid group and 2407±388 mL for the placebo group (P>.05). For the secondary outcomes, D-dimer levels were lower in the tranexamic acid group than in the placebo group 24 hours after delivery (2.1±1.2 µg/mL vs 4.3±2.4 µg/mL; P<.001).
Prophylactic tranexamic acid treatment did not decrease the mean calculated blood loss. Significantly less participants had a calculated blood loss >2000 mL in the tranexamic acid group than in the placebo group and had lower levels of D-dimer at 24 hours.
Tranexamic acid and obstetric hemorrhage: give empirically or selectively?
2021, International Journal of Obstetric Anesthesia
Citation Excerpt :
In 2003, Gai et al. reported the results of a RCT in women who underwent elective cesarean delivery. Patients who received 1 g TXA (n=91) had a significantly lower blood loss volume compared with those (n=89) who received no treatment (352 ± 148 mL vs. 439 ± 191 mL; P=0.002).46 Since these initial studies, a large number of RCTs have been conducted to compare the effect of 1 g IV TXA (10 min before the skin incision in cesarean deliveries) with a control group (placebo or no treatment), in addition to a uterotonic drug, on the incidence of blood loss after vaginal and pre-labor cesarean deliveries.47–58
Antifibrinolytic agents such as tranexamic acid (TXA) inhibit the fibrinolytic pathway and protect blood clots from being degraded, thereby promoting hemostasis. They have been used to reduce blood loss in various settings including obstetrics. Based on current evidence, TXA can be considered as a therapeutic adjunct to control postpartum hemorrhage (PPH) after vaginal and cesarean deliveries, with earlier administration preferred. This strategy has been demonstrated to reduce mortality due to bleeding (but not the incidence of transfusion) in developing countries. On the other hand, the benefit-risk ratio of TXA has not been fully assessed in developed countries which have much lower PPH-related mortality rates and better access to other management modalities. As a proposed prophylactic agent to prevent PPH, the level of evidence is currently insufficient to recommend the routine use of TXA to prevent blood loss after vaginal and cesarean deliveries. The results of large new multicenter studies assessing the impact of TXA on maternal blood loss-related outcomes after cesarean delivery are awaited. While most studies to date have focused on empirical and one-size-fit-all dosing of TXA, more selective and individualized treatment protocols (possibly guided by functional coagulation assays) are needed to pave the way for safer and more effective use of this inexpensive and widely used medication.
Intravenous versus intramuscular oxytocin injection for preventing uterine atonic primary postpartum haemorrhage in third stage of labour: A double-blind randomised controlled trial
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