Effectiveness of tranexamic acid in reducing hidden blood loss during laparoscopic sleeve gastrectomy: a randomized clinical trial

doi:10.21203/rs.3.rs-5241693/v1

Introduction:
Obesity and its related metabolic complications are an increasing challenge for healthcare systems. Bariatric surgery is an effective treatment, but it is associated with potential adverse events, including postoperative bleeding. Enhanced Recovery After Bariatric Surgery (ERABS) protocols aim to reduce length of hospital stay, but they also reduce time for patients monitoring. Tranexamic acid (TXA), an antifibrinolytic agent, has shown promise in reducing bleeding in various surgeries, but its use in bariatric procedures remains under-researched. This study aims to evaluate the effectiveness of TXA in reducing postoperative bleeding following laparoscopic sleeve gastrectomy (SG).

Material and methods:

A single-center, single-blinded, randomized controlled trial was conducted at the University Clinical Center, Medical University of Gdańsk, Poland, between July 2022 and June 2023. A total of 238 patients undergoing SG were randomized to receive either TXA or no pharmacological intervention. The primary outcome was the haemoglobin concentration in abdominal drainage post-surgery. Secondary outcomes included total blood loss, drainage volume, need for blood transfusion, and postoperative complications. Statistical analysis was performed using intention-to-treat and per-protocol strategies.

Results:
A significant reduction in haemoglobin concentration in the drainage samples was observed in the TXA group (p=0.003). However, no significant differences were found in overall blood loss, drainage volume, necessity for blood transfusions or extended hospital stay between groups.

Conclusion:
TXA administration during SG reduces postoperative, abdominal bleeding as measured by haemoglobin concentration in abdominal drainage without affecting overall blood loss. These findings support further research into the routine use of TXA as part of the ERABS protocol in bariatric surgery. Further multicenter trials are needed to confirm the broader applicability and safety of TXA in this setting.

Trial registration: ClinicalTrials.gov (blinded).

TXA seems to be effective in reducing hidden blood loss in laparoscopic sleeve gastrectomy by decreasing intra-abdominal bleeding.

A systemic administration of TXA in patients with multiple stated metabolic syndrome components seems to additionally reduce the overall amount of drainage.

Patients with preopartive coagulation disorders benefit more from TXA administration regarding intra-abdominal bleeding.

Obesity and its metabolic outcomes has become an increasing problem for healthcare. Bariatric surgery is a well-established and safe method for the treatment of obesity and its complications (1, 2). However, bariatric surgery may be associated with adverse events (AEs) such as nutritional deficiencies, anastomotic fistulas, gastrointestinal leaks and haemorrhage (3–5). Bleeding is one of the most common surgical complications in bariatric surgery. Reported rates of haemorrhage in literature vary from 0.5–4% (6). It is also associated with a significant increase in other adverse effects (AE) occurrence (7).

Implementation of enhanced recovery after bariatric surgery (ERABS) (8) resulted in the early mobilization of patients and a reduced length of hospital stay (LOS), therefore reducing the overall time for observation. Patients treated according to the ERABS protocol are discharged on the first postoperative day, unless there are reasons to keep them a day longer in hospital. Here, patient safety is one of the factors to consider. Postoperative bleeding is still one of the most common AE following sleeve gastrectomy (SG) (9) and is associated with higher mortality and morbidity (10). The rate of early (30-day) rehospitalization is estimated at around 6% (11). Bleeding is one of the most common reasons for readmission and requires urgent surgical or endoscopic management, which reduces the cost-effectiveness of bariatric procedures (12–14). To decrease the rate of readmission and increase the patients’ safety, surgical hemostasis becomes even more important to achieve.

The use of tranexamic acid (TXA) in bariatric surgery has been a developing and promising topic in recent years (15). The benefits of TXA usage have already been proven to be successful in reducing intraoperative bleeding in many surgical procedures. In many cases, TXA infusion reduced the need for transfusion after surgery and necessity for surgical intervention (16, 17). TXA is a synthetic derivative of the aminoacid lysine. It exerts its antifibrinolytic effect by a reversible interaction with plasminogen and decreases the formation of protease plasmin, therefore reducing the degradation of fibrin (18). Possible side effects of TXA are seizures, blurred vision and skin rash. Because of its mechanism of action, TXA usage may increase the risk of venous thromboembolism (VTE) (19–22). Obesity itself is associated with higher VTE risk, and undergoing a bariatric procedure and an oral fluid intake restriction can increase this risk even more (23). Based on multi-center randomized trials, the use of TXA as an additional hemostatic factor during surgical procedures has proven to be both effective (16). However, no randomized trial with TXA has been conducted for bariatric patients (23).

Therefore, the aim of this study is to evaluate the effectiveness of TXA administration in reducing the volume and haemoglobin concentration in abdominal drainage after laparoscopic sleeve gastrectomy (SG).

Trial design:

This preliminary study was a single-center, single-blinded controlled clinical trial, with parallel-group design, with the randomization ratio (1:1). Trial protocol is detailed in Supplementary Material 1.

Participants:
Participants were adults qualified for a bariatric procedure in University Clinical Center, (blinded). The qualification for surgery was in accordance with the International Federation for the Surgery of Obesity (IFSO) guidelines and the recommendations of the Bariatric Chapter of the Association of Polish Surgeon (24,25). Positively qualified patients were enrolled during admittance to the hospital for surgical treatment from July 4th, 2022 to June 28th, 2023.

The inclusion criteria were as follows:

Age over 18
Qualification for SG
Obtained consent for participating in the study

The primary (preoperative) exclusion criteria were as follows:

Qualification for a procedure other than SG
Usage of anticoagulative agents in the perioperative period, including:
Indirect thrombin inhibitors (Fondaparinux, UFH, LMWH in therapeutic doses)
Direct inhibitors of factor Xa (NOAC)
Direct thrombin inhibitors (Dabigatran)
Vitamin K Antagonists (VKA: acenokumarol, warfarin)
Platelet aggregation inhibitors (excluding ASA in doses of 75mg per day)
P2Y12 receptor inhibitors
Prior diagnosis of congenital or acquired blood coagulation disorders
Diagnosed allergic reactions to TXA in medical history
Chronic Kidney Disease in stage G3 or more advanced
Chronic hemodialysis
Haematuria in medical history
Seizures in medical history

A written, informed consent was obtained from all participants before the trial began. This clinical trial was registered at www.clinicaltrials.gov (blinded). The registration was performed during the trial. The Consolidated Standards of Reporting Trials (CONSORT) guidelines for reporting randomized trials were followed (26). The study design and protocol were approved by the University Bioethics Committee (NKBBN/439/2022). All procedures performed in this study involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments.

Interventions:

Every patient received a preoperative dose of LMWH (40mg of Enoxaparin sodium) as a prophylaxis according to local hospital guidelines, 12h before surgery. All qualified patients received a single dose of 1g of i.v. TXA bolus at a loading dose of 1g over 10 minutes, within 10 minutes of the induction of anesthesia, preceding the anticipated skin incision. This model of dosing and administration allows the maximum concentration of medication to be achieved throughout the whole procedure time. All procedures were performed by qualified and certified bariatric surgeons following a highly standardized protocol. Preceding the end of the procedure, an abdominal drain was placed alongside the staple line to monitor blood loss in the perioperative period. Drainage placement was performed only for study purposes. On the first postoperative day, the volume of drainage was monitored, and a 5ml sample was taken to perform a CBC in a single, local laboratory with an automated method of evaluation – the result of the test was noted. To standardize the conditions of monitoring blood loss, all peripheral blood samples were taken on the day of admission, and at 5pm on the first day after surgery. Patients were discharged from hospital if the discharge criteria were met (detailed description in the standard hospitalization protocol – Supplementary Material 2). Within 30 days of randomization, the patients were assessed by a qualified physician during a follow-up appointment – a clinical examination for arterial and venous thromboembolism was performed, basic laboratory parameters were measured, and additionally, the Clavien-Dindo score was evaluated(27).

Outcomes:

The primary outcome parameter was the intraperitoneal, postoperative blood loss (defined as mean haemoglobin concentration in the drainage sample, measured through performing a complete blood count (CBC)). The secondary outcomes were: blood loss (defined as the difference between the preoperative and postoperative haemoglobin concentration in the peripheral blood sample), the drainage volume in ml, the haemoglobin mass in drainage (evaluated by multiplying the drainage volume and haemoglobin concentration) the procedure time (minutes), the extended postoperative hospital stay (days), major surgical complications due to bleeding (defined as a Clavien-Dindo score ³3), and necessity for blood transfusion.

Sample size:

No data was available before this trial on the concentration of haemoglobin in abdominal, postoperative drainage after an intravenous administration of TXA. Therefore, a pilot study was commenced. During the period from July 4^th, 2022 to December 19^th, 2022, 142 patients were randomized, from which 123 patients were enrolled in the analysis. The univariate analysis revealed exponential distribution of obtained data. SAS® procedure power having regard to such distributions was performed. It was shown that for sample size of approximately 100 subjects per group the significant (p<0.05) difference in hemoglobin concentration will be expected with the power of test equal 0.8. During 12 months period 238 patients were enrolled into the study. The interim analysis of data confirmed intended power and significance for the difference in hemoglobin concentration between groups. Therefore, the trial was closed.

Randomization:

This was a single-blinded clinical trial. After signing an informed consent, patients were not informed of their allocation to the control and test groups. A block randomization was used to allocate patients to different interventions based on the operating schedule of the center. Block size varied depending on the operating room availability. Patients were assigned to the control and test groups alternately on a weekly basis. To further reduce possible bias, there were different physicians qualifying patients for operation who had no interaction with those physicians scheduling the operations. Moreover, a different physician was responsible for the randomization scheme and the data collection. Data analysis was performed by an independent physician from outside the center who was blinded to the allocation.

Statistical methods:

The collected data were analyzed according to both the intention-to-treat and per protocol principles. Categorical data were presented as numbers and percentages of the analyzed group. Continuous variables were reported using mean and 95% confidence interval for normally distributed data and as median with 5^th-95^th percentile range otherwise. Statistical tests were performed using SAS Studio ver. 3.81. Group comparison for categorical variables was assessed using Chi-square test. ANOVA or Mann-Whitney test were used for normally or non-normally distributed continuous variables respectively. The level of statistical significance was determined as p<0.05.

Between July 1^st, 2022 and June 30^th, 2023, 316 patients were assessed for eligibility. In total, 268 eligible patients were randomly assigned to receive no pharmacological intervention (Control group - CG) or TXA (Test group - TG) (Figure 1).

Additionally, due to missing crucial lab test results, 30 patients were excluded from the trial (CG=12; TG=18). Therefore, a total number of 238 patients (CG=123; TG=115) were included in the analysis. The obligatory 1-month follow-up visit was completed for 97.9% (n=233) of the analyzed patients. Between July 4^th, 2022 and June 28^th, 2023, all the qualified patients underwent surgery. 22 patients originally assigned to the control group (CG) required an intraoperative dose of TXA. However, according to the intention-to-treat approach, they were still analyzed as the control group. All patients originally assigned to the test group (TG) received the allocated intervention. After 12 months of patient recruitment the trial was concluded. The total data-gathering period ended on August 4th, 2023. The baseline characteristics were comparable between both study groups (Table 1).

Table 1: Baseline demographics (Intention-to-treat and per-protocol analysis).

		Intention-to-treat			Per protocol
	CG (n=123)	TG (n=115)	p-value for group comparison	CG (n=102)	TG (n=136)	p-value for group comparison
Age (years)	41 [39.5 - 43.1]	41.4 [39.7 - 43.1]	0.926 ¹	41.2 [39.4 - 43.1]	41.4 [39.7 - 43.2]	0.852 ¹
Female gender	79 (64%)	77 (67%)	0.658 ³	63 (62%)	93 (68%)	0.288 ³
Height (m)	1.72 [1.71 - 1.74]	1.70 [1.58 - 1.90]*	0.753 ²	1.73 [1.71 - 1.74]	1.70 [1.58 - 1.90]*	0.112 ²
Preoperative weight (kg)	119 [90 - 172]	111 [86 - 175]*	0.097 ²	121 [91 - 172]*	111 [86 - 175]*	0.075 ²
Preoperative Body Mass Index (kg/m²)	40 [33 - 53.1]*	38.9 [30.8 - 49.5]*	0.261 ²	39.9 [33.3 - 53.1]*	38.6 [31.4 - 49.8]*	0.167 ²
Maximal weight (kg)	135 [102 - 196]*	127 [94 - 190]*	0.046 ²	135 [104 - 196]*	127 [94 - 190]*	0.047 ²
Maximal Body Mass Index (kg/m²)	45 [36.7 - 59.9]*	44.3 [35.9 - 56.8]*	0.089 ²	45.5 [37.8 - 59.9]*	44.1 [35.4 - 58.3]*	0.163 ²
Diabetes melitus	21 (17%)	20 (17%)	0.948 ³	18 (18%)	23 (17%)	0.882 ³
Hypertension	54 (44%)	51 (44%)	0.945 ³	46 (45%)	59 (43%)	0.792 ³
Dyslipidemia	87 (71%)	77 (67%)	0.530 ³	76 (74.51%)	88 (65%)	0.106 ³
Previous abdominal surgeries	40 (33%)	43 (37.39%)	0.431 ³	31 (30%)	52 (38%)	0.209 ³
Preoperative lab tests
Haemoglobin concentration (g/dl)	14 [13.9 - 14.4]	14 [13.8 - 14.3]	0.495 ¹	14.5 [11.5 - 16.1]*	14 [13.8 - 14.2]	0.790 ²
Hematocrit (%)	43 [41.9 - 43.4]	42.3 [41.7 - 42.9]	0.481 ¹	42.8 [42 - 43.6]	42.3 [41.7 - 42.9]	0.277 ¹
Platelets count (10³/μl)	251 [174 - 394]*	263 [252.5 - 272.5]	0.746 ²	255 [174 - 388]*	263 [176 - 355]*	0.982 ²
White blood cells count (10³/μl)	8 [5 - 12]*	7.8 [7.4 - 8.1]	0.206 ²	7.8 [5 - 11.3]*	7.6 [4.9 - 11.4]*	0.396 ²

For normally distrubuted continous variables data are presented as mean with 95% confidence interval otherwise as median with 5th-95th percentile range (*). Nominal variables are presented as N (percentage of the relevant group). Between groups differences were tested using: Anova ¹, Mann-Whitney U ² and chi-square ³ tests, respectively.

Intention to treat analysis:

Primary endpoint:

A statistically significant difference in the mean haemoglobin concentration in the drainage samples was found between the study groups in both the intention-to-treat (CG=1.4g/dL, TG=0.7g/dL; p=0.011) and per protocol analysis (CG=1.7g/dL, TG=0.7g/dL; p=0.001) (Table 2).

Secondary endpoints:

Table 2 presents an analysis of the data of patients. The haemoglobin mass evaluated from the drainage sample differed between the study groups (CG=0.4g, TG=0.2g; p=0.005). There was no difference in mean drainage volume (CG=40ml, TG=40ml; p=0.187). What is more, postoperative blood loss, measured as the difference between pre- and postoperative peripheral blood mean haemoglobin concentration, did not differ significantly between the groups (CG=0.7g/dL, TG=0.5g/dL; p=0.103). No significant difference was found in the mean procedure time (CG=55min, TG=54min; p=0.880). An extended postoperative stay, defined as a deviation from discharge on the first day after the procedure, was noted in 7 patients in the control group; 3 patients in the test group required a prolongation of hospital stay. There was no significant difference between the study groups regarding blood transfusions. In the control group, 2 patients required a transfusion of a total of 5 red blood cell packs and 2 freshly frozen plasma packs; in the study group, 1 patient required a transfusion of 3 red blood cell packs. No VTE or peripheral arterial thrombosis events were noted at the 1-month follow-up visit in both groups.

Table 2: Postoperative outcomes (Intention-to-treat and per-protocol analysis).

		Intention-to-treat			Per protocol
	CG (n=123)	TG (n=115)	p-value for group comparison	CG (n=102)	TG (n=136)	p-value for group comparison
Procedure time (min)	55 [40 - 90]*	54 [39 - 91]*	0.880 ²	55 [40 - 88]*	55 [40 - 95]*	0.408 ²
Postoperative lab tests from peripheral blood sample:
Haemoglobin concentration (g/dl)	13.5 [13.2 - 13.7]	13.5 [13.3 - 13.8]	0.751 ¹	13.8 [10.9 - 15.4]*	13.5 [13.3 - 13.7]	0.407 ²
Hematocrit (%)	40.6 [39.9 - 41.4]	40.9 [40.3 - 41.5]	0.613 ¹	40.7 [39.9 - 41.5]	40.8 [40.2 - 41.4]	0.873 ¹
Platelets count (10³/μl)	255 [171 - 383]*	258 [247.4 - 268.6]	0.888 ²	257.5 [171 - 371]*	257 [162 - 346]*	0.913 ²
WBC count (10³/μl)	10.9 [10.4 - 11.4]	11.1 [10.6 - 11.5]	0.703 ¹	10.9 [10.4 - 11.4]	11.1 [10.7 - 11.6]	0.437 ¹
Difference in haemoglobin concentration (g/dl)	0.7 [0.5 - 0.9]	0.5 [0.4 - 0.7]	0.103 ¹	0.7 [0.5 - 0.9]	0.5 [0.4 - 0.7]	0.089 ¹
Difference in hematocrite (%)	2 [1.5 - 2.5]	1.4 [1 - 1.9]	0.072 ¹	2.1 [1.6 - 2.6]	1.5 [1.1 - 1.9]	0.065 ¹
Difference in platelets count (10³/μl)	1.5 [-4.1 - 7.1]	7 [-51 - 47]*	0.340 ²	3 [-2.9 - 8.9]	6 [-52 - 47]*	0.771 ²
Difference in WBC count (10³/μl)	-2.9 [-3.4 - -2.5]	-3.3 [-3.7 - -2.9]	0.245 ¹	-3 [-3.4 - -2.5]	-3.2 [-3.6 - -2.8]	0.428 ¹
Postoperative lab tests from drainage sample:
Drainage volume (ml)	40 [10 - 140]*	40 [5 - 101]*	0.187 ²	40 [5 - 160]*	40 [5 - 101]*	0.520 ²
Haemoglobin concentartion (g/dl)	1.4 [0.1 - 7.1]*	0.7 [0.1 - 6.1]*	0.011 ²	1.7 [0.1 - 7.7]*	0.7 [0.1 - 6.1]*	0.001 ²
Hematocrit (%)	4 [0.1 - 22.9]*	1.8 [0.1 - 19.4]*	0.029 ²	5 [0.1 - 23.4]*	1.8 [0.1 - 19.4]*	0.003 ²
Haemoglobin mass (volume x concentration) (g)	0.4 [0 - 5.6]*	0.2 [0 - 3.4]*	0.005 ²	0.6 [0 - 9.6]*	0.2 [0 - 3.5]*	0.006 ²

For normally distrubuted continous variables data are presented as mean with 95% confidence interval otherwise as median with 5th-95th percentile range (*). Nominal variables are presented as N (percentage of the relevant group). Between groups differences were tested using: Anova ¹, Mann-Whitney U ² and chi-square ³ tests, respectively.

Subgroup analyses:

As mentioned in the study protocol, due to clinical relevance, 2 additional subgroup analyses were performed. The first analysis considered the preoperative presence of metabolic syndrome components during the examination of patients on admittance to the hospital (obesity, arterial blood hypertension, type 2 diabetes, hyperlipidemia), known to increase the general complication rate in bariatric surgery. The analysis was carried out in subgroups characterized by the sum of metabolic syndrome components. Patients with a higher number of obesity complications had a significantly smaller drainage volume after TXA administration intraoperatively (Figure 2); however, no significant differences were noted in haemoglobin concentration and mass in drainage samples in those subgroups.

An additional subgroup analysis was created considering preoperative INR values. Patients with INR<1 did not have any significant differences in volume, haemoglobin concentration and mass in the drainage sample. However, patients with the INR value >1 had significantly smaller haemoglobin concentration and mass in the drainage sample (Figure 3).

Unintended effects and harm

The Clavien-Dindo scale was used to evaluate complications during the obligatory 1-month follow-up visit. Events considered as major complications (CD grade ³3) were noted in 6 patients in the control group, and 3 patients in the test group. All complications are listed in Supplementary Table 1. Additionally, there was no need for upper endoscopy for bleeding in both study groups.

Per protocol analysis:

Both primary and secondary outcomes were analysed as stated above for the patients allocated to control group (CG) and test group (TG) according to per protocol principle. Results are presented in Table 2.

This randomized clinical trial aimed to evaluate the effectiveness of Tranexamic Acid (TXA) on the intraperitoneal, postoperative bleeding in a laparoscopic sleeve gastrectomy cohort. Our findings are in line with previous studies regarding a decrease in blood loss after TXA administration (35, 36). In the literature, the postoperative haemoglobin level reduction, which occurs without any significant surgical bleeding is mostly associated with the effect of hidden blood loss (28, 29). This effect significantly increases the cumulative blood loss and has been comprehensively documented in both orthopedic and abdominal surgical settings (30–32). The clinical repercussions of hidden blood loss may extend to the requisition of blood transfusions, the undertaking of extensive diagnostic evaluations, and the prolongation of LOS (33, 34). The ERABS protocol guidelines advisedly contraindicate the placement of abdominal drains postoperatively, further accentuating the risk of hidden blood loss and underscoring the necessity for augmented hemostatic strategies to bolster postoperative recovery.

Our main study parameter - haemoglobin level evaluation performed on the abdominal drainage sample may provide valuable, additional information concerning the source of potential bleeding, supporting physicians with additional information possibly reducing the risk of unneccesary diagnostic procedures. Moreover, our findings demonstrate a reduction in haemoglobin concentration in abdominal drainage after TXA administration with no effect on the drainage volume. This fact may indicate that while TXA influences the nature of the fluid, it does not impact the overall volume of fluid produced postoperatively. Our study suggests that TXA administration may allow the complete implementation of the ERABS protocol decreasing the risk of undiscovered intraperitoneal bleeding, therefore promoting avoidance of routine drainage placement.

Despite the reduction in mean haemoglobin concentration in abdominal drainage, we did not observe significant differences in the overall postoperative blood loss measured in a whole blood sample, the operative time, or the need for an extended LOS between the study groups. This might indicate that TXA administration is effective in reducing immediate surgical bleeding, but its impact on other surgical outcomes may be limited (37). We did not find a significant difference in the operative time. This might suggest that TXA does not add complexity or prolong the duration of the operative procedure. Although other studies, including meta-analyses, in the field of bariatric surgery discovered a positive effect of TXA on blood loss (38, 39), our study shows that the lack of statistical difference in the blood loss measured from peripheral blood can be contributed to the different study design. According to literature, the rate of postoperative (30-day) VTE in a group of patients undergoing bariatric surgery varies from 0.14–1.9% (41, 42). Available research state that the administration of TXA did not cause a significant increase in VTE episodes within 30 days of surgery (40). In our study, no incidence of 30-day VTE was noted, however the design and limited power does not allow to draw any conclusions on safety profile of TXA administartion (43). The overall rate of VTE after abdominal surgeries is low, probably thanks to the standard application of antithrombotic prophylaxis (45).

Additionally, TXA administration resulted in the reduction of abdominal drainage volume among patients with at least 4 components of metabolic syndrome, proven by one sub-analysis included in this study. This particular subgroup of patients may benefit the most from routine, intraoperative TXA administration. These finding are in line with other studies from the fields of orthopedics and breast surgery (46–48). However, no studies on this topic have been conducted in metabolic surgery to this date.

Moreover, we noted that in the group of patients with a preoperative international normalized ratio (INR) greater than 1, the usage of TXA translates into a reduction in haemoglobin concentration in the abdominal drainage sample. This finding suggests that TXA administration is more effective and beneficial for patients with preoperative coagulation disorders, which is in line with other studies on this matter (49–51).

This study has several limitations. The single-blind design may increase the risk of bias. The single-center setting limits the sample sizes, therefore more randomized clinical trials are needed to prove the results. On the other hand, to date and to our knowledge, no multi-center trials on TXA applications in metabolic surgery have been published, which reduces the possibility for a comparison of data and results. Other crucial limitaions of this study are: it is underpower to prove safety profile of TXA administration, it is probably underpowered to detect differences in AEs rates, additionally different dosing of TXA were used between different studies which limits the possibility to compare the results with other trials.

In conclusion, TXA administration may be an effective addition to the ERABS protocol as it may reduce the risk of the effect of hidden blood loss in patients undergoing metabolic surgery. This study provides a rationale of a definitive, multicenter randomized clinical trial to allow the widespread adoption of routine intraoperative TXA administration to the ERABS protocol and full assessment of other potential benefits (reduction of blood tranfusions, limitation of prolonged hospital stay).

The authors declare no conflict of interest.

No external funding was aquired for the purpose of this study.

The study design and protocol were approved by the University Ethics Committee (NKBBN/439/2022). All procedures performed in this study involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments.

A written, informed consent was obtained from all participants before the trial began.

Author Contribution

KB., MS were involved in conception and design of the study. KB, MS were co-lead investigators.MS obtained ethics approval.KB prepared figures and tables.KB, MS, PN drafted manuscript. All authors edited, revised and approved the final version of the manuscript.

Data Availability

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.

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No competing interests reported.

Effectiveness of tranexamic acid in reducing hidden blood loss during laparoscopic sleeve gastrectomy: a randomized clinical trial

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