European Journal of Cardiovascular Medicine

Total Abdominal Hysterectomy (TAH) is a commonly performed major surgery in gynaecology worldwide. It is considered as a definitive management for a large number of benign uterine conditions that are refractory to medical management, including symptomatic uterine myomas, abnormal uterine bleeding (AUB), adenomyosis, and severe endometriosis. Uterine fibroids, in particular, represent the key indication for hysterectomy, resulting in 35% of all such procedures.¹ While often curative and significantly improving a patient's quality of life, TAH is not without substantial risks. The central clinical challenge associated with TAH is significant perioperative haemorrhage. The uterus possesses a rich dual blood supply from the uterine and ovarian arteries, and the surgical procedure necessitates extensive tissue dissection through highly vascularized planes, including the uterine pedicles, broad ligament, and vaginal cuff. ²This inherent procedural nature creates a high risk of substantial blood loss. Perioperative hemorrhage is a primary cause of patient morbidity, leading to complications such as intraoperative hemodynamic instability, postoperative anemia, increased susceptibility to infection, the need for transfusion of blood and blood products, and prolonged hospital stays and recovery periods. The requirement of transfusion, which is potentially lifesaving introduces its own set of risks, including transfusion reactions, transmission of infectious diseases and immunomodulation.³

As a response to this challenge, a number of strategies have been adopted to mitigate blood loss during TAH, ranging from meticulous surgical technique to the usage of pharmacological agents. Among the pharmacological agents, Tranexamic Acid (TXA) has emerged as a promising, targeted intervention. Tranexamic acid is a synthetic analogue of lysine that functions as a potent antifibrinolytic agent. TXA effectively stabilizes clots that form at the site of surgical trauma, thereby reducing bleeding.⁴

Tranexamic Acid

Developed in 1962 by Shosuke and Utako Okamoto at Kobe University, Japan.

• A synthetic antifibrinolytic agent designed to reduce bleeding.
• Introduced globally in the 1970s–80s for menorrhagia, trauma, and surgical bleeding.
• Major trials: CRASH-2 (2010) and WOMAN Trial (2017) – established its life-saving role in trauma and postpartum hemorrhage.⁵

Mechanism of Action

Tranexamic acid is a synthetic lysine analogue.

• Competitively inhibits activation of plasminogen to plasmin.⁴
• Prevents fibrin degradation and stabilizes blood clots.
• Does not promote new clot formation.

Dosage

1. Oral (Menorrhagia): 1 g orally 3–4 times daily for up to 5 days during menstruation.
2. Intravenous (PPH or Trauma):

• 1 g IV over 10 minutes (within 3 hours of onset).
• Repeat 1 g IV after 30 min–3 hrs if bleeding continues (WOMAN/CRASH-2 protocol).⁵

1. Surgical Use: 10–15 mg/kg IV before incision; may repeat after 3–4 hours.

• Absorption: 30–50% oral bioavailability.
• Distribution: Widely distributed, crosses placenta, minimal CNS penetration.
• Protein binding: ~3%.
• Metabolism: Minimal hepatic metabolism.
• Excretion: 95% unchanged in urine.
• Half-life: 2–3 hours.

Safety Profile

Conventionally, intravenous use of antifibrinolytics is seen in a lot of surgical procedures. Concerns that often arise with intravenous use of tranexamic acid include allergic reactions, thrombosis, increased risk of seizures, and renal impairment.

Looking at the safety issues with intravenous administration, a growing trend is witnessed in the topical use of tranexamic acid (prolonged in renal impairment).

AIM & OBJECTIVES

Aim

To determine the prophylactic role of tranexamic acid in reducing perioperative blood loss in total abdominal hysterectomy.

Objectives

Primary Objective

The principal objective was to understand the effectiveness of prophylactic tranexamic acid in comparison with placebo in reducing perioperative blood loss.

Secondary Objective

• Evaluating hemoglobin drop.
• Requirement of blood transfusion.
• Safety profile of the drug in women taken up for hysterectomy for benign conditions.

Study Design

The study is a prospective, double blinded randomized controlled trial which was undertaken and accomplished at the Department of Obstetrics and Gynaecology, Tezpur Medical College and Hospital, Tezpur, Assam, conducted for period of one year from 1^st Sept 2024 to 31^st Aug 2025.

Source of Data

Patients that had been admitted in the department of Obstetrics and Gynaecology, TMCH with indication for abdominal hysterectomy.

The patients suitable for the study were divided into 2 groups:

Group 1: Patients undergoing abdominal hysterectomy and receiving Intravenous Tranexamic acid.

Group 2: Patients undergoing abdominal hysterectomy and receiving placebo.

Sample Size

The number of patients constituted the sample and included in the study were in accordance with the formula given below:

n= Zα/2² P(1-P)/e², where n is the sample size, Z is the statistic corresponding to level of confidence , P is expected prevalence.

Considering the expected number of abdominal hysterectomies done in TMCH as 100 in one year as the study population, the minimum number of sample size with 95% confidence with 5% type 1 error and 5% absolute error was found to be 66. Assuming 10% lost to follow up and after rounding up, the sample size will be 80.

Randomization

Altogether 80 women were recruited for the study keeping in view their eligibility criteria. The study was done in two groups.

Sequence Generation

Randomisation of allocated groups was done by computer generated random numbers.

Allocation Concealment Mechanism

The allocated groups were concealed in serially numbered opaque envelopes with TA or NS written on them. Envelopes were revealed only after recruitment of groups. Patient allocation was performed by an independent individual who was not otherwise part of this study.

Implementation of Blinding

The envelopes were taken up and opened sequentially just before pushing the injection by an assigned nurse, who prepared the injection as mentioned in the card inside for that particular patient and handed over the syringe to the anaesthetist performing the procedure. Input date, time, patient ID, results after the procedure, etc. were recorded by the anaesthetist on a sheet which was present inside the envelope. The envelope was sealed and preserved in a secured place for tranexamic acid (test group) and 40 women got placebo (normal saline) which acted as the control group. The trial was appropriately blinded- both the participants and the surgeons performing the surgery. In case of blood loss despite giving intervention, proper protocol was followed and an appropriate medical and surgical procedure was used for hemostasis and noted properly. A previously prepared set questionnaire was filled through proper history taking, examination with informed consent of patient/ next of kin. The study was done after taking due clearance from institutional ethical committee. Each Clinical finding was recorded in proforma with investigations.

• Placebo group (n=40) received 10 ml intravenous normal saline, while Tranexamic acid group (n=40) received 1 g tranexamic acid in 10 ml normal saline intravenously 5 minutes before skin incision.
• All patients taken up for hysterectomy were given standardized regional or general anesthesia.
• All procedures were performed by experienced gynecologists using standardized surgical techniques for total abdominal hysterectomy. The surgical approach included careful hemostasis with electrocautery and suture ligation of vessels.

Eligibility Criteria

All women with benign conditions admitted in gynae ward of TMCH with indication for abdominal hysterectomy.

Inclusion Criteria

• Women selected for total abdominal hysterectomy for benign conditions: myoma, menorrhagia, abnormal uterine bleeding, adenomyosis and endometrial hyperplasia.
• Normal coagulation parameters
• Written informed consent.

Exclusion Criteria

• History of thromboembolic disease
• Cardiac, Renal or Hepatic dysfunction
• Coagulopathy or bleeding disorders
• Allergy to Tranexamic acid
• Malignant conditions
• Emergency procedures

Ethical Consideration

Ethical approval to conduct the study was taken from Tezpur Medical College and Hospital Ethical Committee. (IEC no- 028/2024/TMC&H). Before conducting the study, information regarding the study was explained to patient and patient’s attendant. Oral and written consent have been taken. CTRI registration was done: CTRI/2025/03/081587

Method of Collection of Data

All the patients fulfilling the inclusion and exclusion criteria were explained about the purpose of the study. A written informed consent was taken from the patients. A detailed history and physical examination was done in all included patients as per a pre-determined proforma.

Sampling Method

For sampling, in case of both the Control Group and Treatment Group, Simple Random Sampling technique without Replacement (SRSWOR) was used since the researcher was not aware of any confounding effect/variable that may introduce heterogeneity amongst the subjects.

Both the placebo and tranexamic acid groups consisting of 40 patients each were thoroughly analysed, compared and results were obtained in the form of primary and secondary outcomes, which showed significant difference. Also the baseline characteristics of both groups were analyzed and were found to be quite similar.

Primary Outcome Measures

Estimated Blood Loss

• Pre- and post-procedure weights of surgical sponges and drapes
• Volume of blood in suction containers.
• Blood-soaked materials were weighed, with 1g weight increase equivalent to 1mL blood loss.

Laboratory Parameters

• Preoperative hemoglobin and hematocrit (after 24 hours of surgery)
• Postoperative hemoglobin and hematocrit (after 24 hours post-surgery)
• Calculation of hemoglobin and hematocrit changes

Secondary Outcomes

• Blood transfusion requirements.
• Operative time.
• Hospital stay duration.
• Adverse effects (nausea, vomiting, allergic reactions, thromboembolic complications).

Statistical Analysis

Appropriate statistical software (SPSS) was used to analyse the gathered data. Continuous variables were expressed in context of mean ± standard deviation and compared using independent t-tests. Categorical variables were expressed in terms of frequencies and percentages, compared using chi-square tests. A p-value <0.05 was considered statistically significant.

Primary Outcome

Tranexamic acid caused significant decline of mean estimated blood loss in comparison to placebo (113.25 ±33.92 mL vs 231.50 ±56.68 mL, p<0.001).

Secondary outcomes

Blood Transfusion Requirement

Blood transfusion was required in 7.5% of tranexamic acid group versus 15.0% of placebo group (p=0.479).

Perioperative Haemoglobin and Haematocrit Drop

The haemoglobin drop was significantly lower in the group that received intravenous tranexamic acid (-0.25 ±0.09 g/dL vs -0.53 ±0.13 g/dL, p<0.001).

Baseline Characteristics

Both groups were comparable in terms of age, parity, and preoperative hemoglobin levels. There was a statistically significant difference in weight between the groups, with the placebo group having higher mean weight.

Operative Time and Duration of Hospital Stay

Adverse Effects

• The mean operative time and duration of stay in hospital were comparable between both the groups with no statistically significant differences (p>0.05).
• No major side effects were observed in either group. Minor side effects included nausea and vomiting in a small number of patients.
• The study highlighted statistically significant differences in all primary outcomes with large effect sizes, hence suggesting not just statistical significance of the study but also clinical relevance of the findings.

The effectiveness of tranexamic acid in reduction of haemorrhage and transfusion requirements is well-established across a broad spectrum of surgical disciplines, including cardiothoracic, orthopedic and trauma care.⁵ In obstetrics, its use is recommended by the World Health Organization for the management of postpartum hemorrhage. Within gynaecology, systematic reviews and meta-analyses have demonstrated its benefit in lowering blood loss in procedures like myomectomy. However, the evidence specific to hysterectomy, while largely positive, includes some conflicting reports where no significant benefit was observed. This highlights a potential knowledge gap and underscores the necessity for further well-designed, randomized clinical trials to provide definitive evidence in this specific, high-volume surgical context.⁶ Also, reports of data published regarding thromboembolic events with administration of intravenous tranexamic acid are quite limited and meta-analyses do not suggest any increased risk, however the potential risk of development of thrombosis calls for further evaluation and introduction of alternative hemostatic strategies.⁷ Among the strategies used for hemostasis that were reported, the best strategy is yet to be established.

Considering the positive impact of tranexamic acid on hemostasis in surgical procedures in other specialties, perhaps changes in dosage and administration regimens might prove to be a game changing method in lowering perioperative hemorrhage in hysterectomy.

Therefore, this study was done to rigorously evaluate the efficacy and safety aspect of a standardized, single prophylactic intravenous dose of Tranexamic Acid in lowering perioperative hemorrhage and its associated morbidities in patients undergoing Hysterectomy at our institution.

The Danish Hysterectomy and hysteroscopy Database (DHHD) have shown high rate of complication ranging between 16-18% from 1998-2006, of which perioperative blood loss remains the leading cause.⁸

A Cochrane review of randomized controlled trials (RCTs) comparing TXA with placebo in almost 5000 patients undergoing non-gynecologic surgery showed a reduction in requirement transfusion of blood by 39% (relative risk [RR], 0.61; 95% confidence interval [CI], 0.53–0.70) without an increased risk in venous thromboembolism (VTE) or other adverse perioperative outcomes.²

This randomized controlled trial demonstrates that prophylactic administration of tranexamic acid causes significant reduction in intraoperative bleeding during total abdominal hysterectomy. The 51% reduction in estimated total blood loss observed in our study is consistent with previous meta-analyses showing that TXA reduces surgical bleeding by approximately 34% across various procedures.

Topsoee et al. (2016) reported that the administration of TXA reduced blood loss by 40% during benign abdominal hysterectomy,⁶ while Nivedhana et al.(2018) observed a 38% reduction in perioperative hemorrhage among Indian women who underwent abdominal hysterectomy.⁹ Arvind et al. (2024) demonstrated a significant effect, noting a 55% decrease in intraoperative bleeding after pre-incision TXA administration.¹⁰ Thus, the current study’s findings fall within the expected values as derived from similar studies and are comparable to international and Indian data. The haemoglobin drop in our study was reduced by 47% in the TXA group (0.25 g/dL vs 0.53 g/dL), having close resemblance to the findings of Mitra et al. (2022), who documented a 45% reduction with intravenous TXA.¹¹

Although blood transfusion requirements were lower in the TXA group (7.5% vs 15%), the difference did not reach statistical significance-similar to the trend reported by Sallam & Shady (2019), where transfusion reduction did not meet significance despite substantial blood-loss reduction.⁷ No thromboembolic events or major adverse effects were observed, reaffirming the strong safety profile of TXA demonstrated in larger surgical trials. Overall, our study supports TXAas a safe, effective intervention that significantly reduces perioperative blood loss in total abdominal hysterectomy.

Prophylactic administration of tranexamic acid is safe, well tolerated, and significantly lowers perioperative blood loss during total abdominal hysterectomy.

Its use can lower hemoglobin drop and decrease transfusion requirements, thereby improving perioperative outcomes without increasing adverse effects.

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