DISCUSSION
The majority of hysterectomies, around 90%, are performed for benign conditions, such as fibroids causing abnormal uterine bleeding [1]. There is no universal agreement between gynecologists about the optimum method of hysterectomy, and many clinicians believe that different pathologies require different surgical approaches. [2] Depending on their location, size, and number, fibroids can be removed using hysteroscopic, laparoscopic, and laparoscopically assisted or (mini) laparotomy-based procedures. In the ACOG Committee Opinion No. 444, the Committee on Gynecologic Practice concluded, Vaginal hysterectomy is the approach of choice whenever feasible, based on its well-documented advantages and lower complication rates. [18] Johns et al. [19] reviewed 2,563 hysterectomies performed for non-malignant indications, and they concluded that LAVH was safe with similar complication rates as abdominal or vaginal hysterectomy, and was superior to abdominal hysterectomy (AH). English et al. (2019) showed that in their study, there were 18,033 hysterectomies for benign indications from 61 hospitals. [20]The median estimated blood loss was 100 mL, and the 90th percentile estimated blood loss was 400 mL. It was shown that there were increased risks of transfusion, readmission, reoperation, length of stay, and major postoperative complications with estimated blood loss greater than 400 mL. The risk factors for estimated blood loss greater than 400 mL included abdominal surgery compared with laparoscopic hysterectomy (adjusted odds ratio [aOR] 2.8, CI 2.3-3.5), surgical time longer than 3 hours (aOR 3.9, CI 3.3-4.5), and specimen weight greater than 250 g compared with less than 100 g (aOR 4.8, CI 3.9-5.8). Adhesive disease, being younger than 40 years of age, having a body mass index greater than 35, and the need for a preoperative transfusion were also statistically significantly associated with estimated blood loss greater than 400 mL. [20] Peipert et al. [4] demonstrated that patients with excess blood loss >750 mL had a 3.7-fold increase in febrile morbidity after hysterectomy. Surgery affects the coagulation systems and consequent to the increased release of plasminogen activator inhibitor, the fibrinolytic system shuts down, thus leading to coagulopathy and bleeding. [3] A normal woman can tolerate a blood loss of up to 1000 mL with a minimal effect on their health status, whereas, in a woman with severe anemia or cardiovascular disease, a blood loss of as little as 200 mL may be life-threatening and require additional intervention. [6]. A number of pharmacological agents have been used to reduce perioperative blood loss, and these include the anti-fibrinolytic drugs aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA). A popular conservative approach is to minimize perioperative bleeding through the prophylactic use of anti-fibrinolytic agents. [4] Excessively rapid dissolution of hemostatic fibrin (hyperfibrinolysis) results in excessive or recurrent bleeding and can be prevented by anti-fibrinolytic drugs, which stabilize the fibrin clot. The two commercially available anti-fibrinolytic agents, tranexamic acid(TXA) and e-aminocaproic acid(EACA) are synthetic derivatives of the amino acid lysine and act by blocking the action of plasmin. [5] In a Cochrane review addressing TA’s efficacy in all types of surgery, a significant reduction of bleeding was found corresponding to a mean of 414 ml. [21] In addition to inhibiting plasmin, tranexamic acid also competitively inhibits the activation of trypsinogen by enterokinase, noncompetitively inhibits trypsin, and weakly inhibits thrombin. Dunn et al. (1999) showed that perioperative treatment with tranexamic acid (most commonly as an intravenous loading dose of 10 mg/kg followed by an infusion of 1 mg/kg/hour) resulted in significant reductions in postoperative blood losses (mostly measured over 12 to 24 hours) in randomized, double-blind comparisons with placebo in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). [7] Maddali et al. (2007), Casati et al. (2002) showed that intravenous tranexamic acid was significantly (p < 0.05–0.0001) more effective than placebo in reducing postoperative blood loss and transfusion requirements in patients undergoing CPB. [8,9]. Tranexamic acid has also demonstrated efficacy in the treatment of bleeding during pregnancy, such as that associated with placental abruption. [7] The WOMAN trial showed that TXA reduces death due to bleeding in women with PPH by about one-fifth. When given within 3 hours of giving birth, it reduces maternal death due to bleeding by around one-third. [10] [11]. Kouides et al. (2009) conducted the trial to test the efficacy of tranexamic acid in the treatment of heavy menstrual bleeding. [12] Lukes et al. demonstrated that oral tranexamic acid treatment was well tolerated and significantly improved both menstrual blood loss and health-related quality of life in women with heavy menstrual bleeding. [13] The most frequently reported adverse events include headache, nausea, vomiting, diarrhea, dyspepsia, dysmenorrhoea, dizziness, back pain, numbness, and anemia. Where stated, most adverse events were of mild or moderate severity. [5].
Cumulative meta-analysis showed that reliable evidence that tranexamic acid reduces the need for transfusion has been available for over ten years. [14] Topsoee et al. (2016) showed that intraoperative total blood loss was reduced in the group treated with tranexamic acid compared to the placebo group when estimated both subjectively by the surgeon and objectively by weight (98.4 mL vs. 134.8 mL, P = .006 and 100.0 mL vs. 166.0 mL, P = .004). The incidence of blood loss ≥500 mL was also significantly reduced (6 vs. 21, P = .003), as well as the use of open-label tranexamic acid (7 vs. 18, P = .024). Furthermore, the risk of reoperations owing to postoperative hemorrhage was significantly reduced in the tranexamic acid group compared to the placebo group (2 vs. 9, P = .034). Celebi et al., randomized women with advanced-stage ovarian cancer patients to 15 mg/kg IV TXA or the same volume of placebo immediately before surgery. Outcomes in the present study included a significantly lower mean estimated blood loss and decreased need for transfusion in the TXA group. [22] Goswami et al. had compared the efficacy of two different doses of TXA in their study and inferred that 15 mg/kg dose was more effective than 10 mg/kg dose without an increase in adverse effects. [15]