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]