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Current Clinical Pharmacology, 2018, 13, 136-139

CLINICAL TRIAL STUDY
ISSN: 1574-8847
eISSN: 2212-3938

The Effect of Tranexamic Acid on Preventing Post-partum Hemorrhage

Due to Uterine Atony: A Triple-blind Randomized Clinical Trial
BENTHAM
SCIENCE

Mahvash Zargar1,* Roshan Nikbakht1 and Mahzad Ahmadi2

1
Associate Professor of Obstetrics and Gynecology, Fertility, Infertility and Perinatology Research Center, Ahvaz
Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Fertility, Infertility and Perinatology Research Center, Ahvaz
Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract: Background: Postpartum haemorrhage (PPH) is an important cause of early maternal

 death which needs to be controlled.
Current Clinical Pharmacology

 Objective: This study was designed to compare the effect of intravenous tranexamic acid (TXA)
 and prostaglandin analogue on reducing PPH resulted from uterine atony in women undergoing C
section or vaginal delivery.

Method: A randomized, triple-blind, placebo-controlled study was conducted on 248 pregnant
A R T I C L E H I S T O R Y women with PPH due to uterine atony who were randomly assigned into two groups of TXA as the
intervention group (n=124) and prostaglandin analogue as the control group (n=124). The interven-
Received: June 16, 2017 tion group received 4 g TXA for an hour and then 1 g over 6 hours infusion intravenously and the
Revised: January 29, 2018
Accepted: April 16, 2018 control group received prostaglandin analogue.
DOI: Results: Postoperative bleeding did not significantly differ between the two groups (68.2±6.1 ml
10.2174/1574884713666180507101002

and 69.1±175.73 ml, respectively, P =0.6). Moreover, hemoglobin declines were 1±0.4 g/dl and
 1.2±0.5 g/dL in TXA and prostaglandin group respectively, indicating that the difference was not
statistically significant (P =0.7).
Conclusion: The results of the present study showed that administrating intravenous TXA had
comparable effects with prostaglandin analogue on reducing PPH in women with uterine atony and
in those undergoing C section or vaginal delivery. Therefore, TXA can be used instead of prosta-
glandin in managing such patients.
Keywords: Tranexamic acid, uterine atony, hemorrhage, pregnancy, antifibrinolytic agents, prostaglandin analogue.

1. INTRODUCTION brinolytic agents which has been utilized in various surgeries

[10]. Also, research on antifibrinolytic agents in significant
The main cause of early maternal mortality is postpartum
hemorrhages has shown that the administration of TXA sub-
haemorrhage (PPH), accounting for about 300,000 deaths
stantially reduces the rate of mortality in the population of
annually in the world [1, 2]. The most causes of PPH include
bleeding trauma patients [11]. On the other hand, three ran-
uterine atony, genital tract trauma, and retained placenta [3-
domized, controlled trials [12-14] have suggested that the
5]. Accordingly, there are guidelines which clearly define the administration of TXA reduces perioperative blood loss and
optimal use of delivery interventions and uterotonic medica-
the incidence of PPH in patients undergoing vaginal or elec-
tions [6]. In contrast, haemostatic medications are not rou-
tive caesarean delivery [7].
tinely used as first-line treatments for PPH [6, 7].
However, this strategy determines that the drug must be
Some studies have demonstrated the relation between
administered before delivery, an option that needs careful
fibrinogen reduction and PPH incidence [8]. Moreover, it has
assessment regarding the benefit-risk ratio before any wide
been well recognized that significant tissue damage can
implementation. A more efficient approach to the manage-
move the haemostatic equilibrium toward elevated fibrinoly-
sis, leading to bleeding [9]. TXA is one of the main antifi ment of PPH could be, as has been suggested recently, to
give TXA after its onset [15]. However, no clinical trial has

been conducted on women with uterine atony.
*Address correspondence to this author at the Azadegan Blvd., Imam
Khomeini Hospital, Fertility, Infertility and Perinatology Research Center,
Therefore, we designed a randomized, controlled study to
Ahvaz, Iran; Mobile: +98 916 118 8199; Tel/Fax: +98 61 32216504; compare the effect of intravenous TXA with prostaglandin
E-mail: dr.zargar199@gmail.com analogue on reducing PPH in women with uterine atony.

2212-3938/18 $58.00+.00 © 2018 Bentham Science Publishers

The Effect of Tranexamic Acid on Preventing Post-partum Hemorrhage
2. MATERIALS AND METHODS
A clinical randomized controlled trial was conducted
on 248 women with PPH who had undergone C section or
vaginal delivery at Imam Khomeini Hospital of Ahvaz Jun-
dishapir University of Medical Sciences (AJUMS), Ahvaz,
Iran.
The study received ethics committee approval of Ahvaz
Jundishapur University of Medical Sciences (ethics code:
ajums.REC.1393.402), and all participants assigned written
informed consent. This randomized, triple-blind, placebo-
controlled study was conducted to evaluate the effect of
TXA in comparison with prostaglandin analogue on reduc-
ing PPH due to uterine atony. Women with uterine atony-
induced PPH after caesarean were included. The interven-
tions were unknown to the patients, the intervention provid-
ers, and the individuals who assessed the outcomes (triple-
blind). The initial procedures included massaging, oxytocin
administration, and serum administration in both groups. The
patients were enrolled in the study according to their haem-
orrhage level after usual interventions for controlling haem-
orrhage.
During operation, blood and fluids were collected in suc-
tion containers. Gauze pads and operation sheets were
weighed before and after usage. Intraoperative blood loss
was calculated as the sum of the blood inside the suction
container and the difference between the weighted gauze
pads and operation sheets before and after surgery. Calcula-
tion of blood loss followed the method of Gai et al. [12]:
"blood from gauze pads and operation sheets=weight of
bloody material – weight of dry material / 1.05". Following
delivery of the placenta, all the patients received intravenous
oxytocin (10 units in 500 mL of normal saline) as an infu-
sion over 20 minutes. In addition, all patients postoperatively
received 30 units of oxytocin during the first 8 hours.
Patients in the intervention group were treated with intra-
venous TXA (TRANEXIP AMP, Caspian Tamin Company,
Iran) (4 g for an hour and then 1 g over 6 hours infusion in-
travenously). TXA had been administered after placental
delivery and the beginning of hemorrhagia. Patients in the
control group with a prostaglandin analogue (Hemabate,
prostaglandin F2 Alpha, Pfizer, USA) (0.25 mg intramuscu-
larly in the uterine muscle every 15 to 90 minutes to a
maximum of 8 doses). Inclusion criteria were women with a
singleton pregnancy between 38 weeks+5 days and 40
weeks’ gestation, who were categorized as class 1 (normally
healthy) based on the American Society of Anesthesiologists
(ASA). Exclusion criteria were a history of cesarean delivery
or abdominal surgery; pregnancy-related complications such
as polyhydramnios, macrosomia, pre-eclampsia or abnormal
placenta; blood disorders such as thrombophilia, anemia, or
coagulopathy; underlying diseases such as cardiovascular,
renal, or liver disorders; or contraindication to TXA (Fig. 1).
Blood transfusion was performed if the hemoglobin level
dropped under 8 g /dL. The analysis was done using descrip-
tive statistics including mean and standard deviation. Com-
parisons of the outcomes in the two groups were performed
either by the chi-square for categorical variables or by the
Student t-test for parametric variables. Data analyses were
Current Clinical Pharmacology, 2018, Vol. 13, No. 2 137
WomenundergoingCsectionorvaginaldeliverywithpostpartum
hemorrhagia(PPH)resultedfromuterineatony
(n=248)
Excludedpatients
(n=0)
Initialproceduresincludedmassage,oxytocinandserumadministration
inbothgroups(n=248)
Treatedwithintravenous Treatedwithprostaglandin
tranexamixacid(TXA) analogue
(n=124) (n=124)
0.25mgintramuscularlyin
4grTXAforanhourandthen1g theuterinemuscleevery15
over6hoursinfusionintravenously to90minutestoa
maximumof8doses
Comparison ofPPHafterdelivery
andhemoglobinlevelreduction
Fig. (1). Flowchart of the study.
performed using SPSS software version 19 (SPSS Inc., IBM,
Chicago, USA). Tests with p-values < 0.05 were considered
significant.
3. RESULTS
The mean age of the woman was 26.5 ± 6.9 and
25.5 ± 7.2 years in TXA and prostaglandin groups, respec-
tively. The mean intraoperative bleeding in TXA group
(929.03 ± 250.29 ml) did not significantly differ from pros-
taglandin group (941.53 ± 175.73 ml) (P= 0.6), Similarly, the
postoperative bleeding did not significantly differ between the
two groups (68.2±6.1 ml and 69.1±175.73 ml, respectively,
P =0.6). Moreover, hemoglobin declines were 1±0.4 g/dl and
1.2±0.5 g/dL in TXA and prostaglandin group, respectively.
Clearly, the difference was not statistically significant
(P =0.7). Almost over 80% of patients in both groups
received any or only one packed cell (P=0.9). A few patients
in both groups (15 vs. 18), however, received 2 or more than
3 blood packed cells transfusion. Of 124 patients in TXA
group, 2 patients had a hysterectomy and similarly 3 patients
in prostaglandin group underwent a hysterectomy. Also, the
mean hospitalization days were 3 days in both groups
(P=0.2) (Table 1).
4. DISCUSSION
The present study demonstrated that intravenous injec-
tion of TXA did not differ with prostaglandin, reducing PPH
resulting from uterine atony in cesarean and vaginal delivery.
Although TXA has recently been utilized to prevent and
reduce intra- and postoperative bleeding in several surgical
types [16-19], it did not make any difference in bleeding in
our study. However, the amount of bleeding was a bit higher
138 Current Clinical Pharmacology, 2018, Vol. 13, No. 2 Zargar et al.

Table 1. Clinical and laboratory properties in TXA and prostaglandin analogue groups of women with post-partum hemorrhage.

Variables TXA (n=124) Prostaglandin (n=124) P value

Age (year) 26.5 (±6.9) 25.5 (±7.2) 0.3

Intraoperative bleeding (ml) 929.03 ±250.29 941.53 ±175.73 0.6

Postoperative bleeding (ml) 68.2 ±6.1 69.1 (±175.73 0.6

Hemoglobin decline (g/dL) 1 ±0.4 1.2 ±0.5 0.7

0 55 (44.4) 52 (41.9)

1 54 (43.5) 54 (43.5)

2 9 (7.3) 12 (9.7)
Received Pack
Cell (Unit) >= 3 6 (4.8) 6 (4.8) 0.9

Hysterectomy 2 (1.6) 3 (2.4) 1

Hospitalization length (Day) 3.73 (±0.98) 3.59 (±0.98, 124) 0.2

Ligation 4 (3.2) 3 (2.4) 1

Values are presented as mean (±SD) or number (percentage).

in the prostaglandin group compared with the TXA group,
though it was not significant.
The rapid reduction in fibrinogen happens during placen-
tal separation. Therefore, it leads to a decrease in the plasmi-
nogen and fibrin production, which in turn stimulates the
fibrinolytic system activation taking 6-10 hours causing
more bleeding. TXA prevents fibrinolysis and consequently
reduces bleeding [20]. There are a few studies which have
assessed the effects of TXA on decreasing bleeding during
the delivery process [9, 11, 13, 14]. In a study to assess the
efficacy of TXA in reducing postoperative blood loss at 2
hours after surgery, it was found that TXA could effectively
reduce the bleeding; however, it could not decrease the blood
loss after placental delivery [12]. In another study, TXA suc-
cessfully reduced blood loss during cesarean delivery [21].
However, similar to the present study, TXA was given re-
gardless of the patient’s weight (4 g of tranexamic acid for
all) which can be one of the limitations in our study limita-
tions. Sekhavat et al. [22] also evaluated the effect of TXA
on bleeding during delivery although their study only as-
sessed postoperative bleeding 2 hours after delivery. They
found a 24% reduction in postoperative bleeding at 2 hours
in the intervention group. A recently published study evalu-
ated the effects of TXA on mortality caused by a postpartum
hemorrhage in more than 20,000 women (10,000 in the in-
tervention group) and found that timing is essential. Tranex-
amic acid has no effect if given more than three hours post-
partum [23]. In our study, TXA was administered after pla-
cental delivery and the beginning of hemorrhagia.
The present study has some certain limitations such as
the measurement of blood loss after placental delivery.
Therefore, skin, muscle, and uterine bleeding were not con-
sidered. In our study, thromboembolic events were not as-
sessed. However, none of our patients presented signs or
symptoms of thromboembolic events. On the other hand,
recent literature has suggested the safety of utilizing this
agent for both pregnant and non-pregnant patients [12, 13,
16-19, 21, 22].
CONCLUSION
The results of the present study showed that administrat-
ing intravenous TXA had comparable effects with prosta-
glandin analogue on reducing PPH in women with uterine
atony. Therefore, TXA can be used instead of prostaglandin
in managing such patients.
ETHICS APPROVAL AND CONSENT TO
PARTICIPATE
The study received ethics committee approval of Ahvaz
Jundishapur University of Medical Sciences (ethics code:
ajums.REC.1393.402).
HUMAN AND ANIMAL RIGHTS
No Animals were used in the study. All research proce-
dures followed were in accordance with the ethical standards
of the committee responsible for human experimentation
(institutional and national), and with the Helsinki Declara-
tion of 1975, as revised in 2008 (http://www.wma.net/en/
20activities/10ethics/10helsinki/).
CONSENT FOR PUBLICATION
All participants assigned written informed consent.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or
otherwise.
ACKNOWLEDGEMENTS
This study was conducted as a specialty thesis in obstet-
rics and gynecology at Ahvaz Jundishapur University of
The Effect of Tranexamic Acid on Preventing Post-partum Hemorrhage
Medical Sciences. Special thanks to Ahvaz Imam Khomeini
Hospital Clinical Research Development Unit (CREDI).
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