Journal of Perinatology (2015), 1–8

© 2015 Nature America, Inc. All rights reserved 0743-8346/15

www.nature.com/jp

ORIGINAL ARTICLE
Tranexamic acid and blood loss during and after cesarean
section: a meta-analysis
H-Y Wang, S-K Hong, Y Duan and H-M Yin

OBJECTIVE: A meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate whether tranexamic acid (TXA) could
significantly reduce blood loss during and after cesarean section (CS) when compared with no TXA.
STUDY DESIGN: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials and Web of Science were searched to
identify RCTs that compared intravenous TXA with no TXA before CS for blood loss. The related data were extracted by two
independent authors. The fixed or random-effect methods were used to combine data.
RESULT: Eleven RCTs were included in this analysis with a total of 1276 women in TXA group and 1255 in no TXA (control) group.
Total blood loss during and after CS was significantly less in TXA group than in control group (mean difference (MD) − 141.61 ml,
95% confidence interval (CI) − 207.09 to − 76.14, P o 0.01). There was a significant reduction in intraoperative and postpartum blood
loss in TXA group as compared with control group (MD − 143.36 ml, 95% CI − 220.38 to − 66.35, P o 0.01; and MD − 38.20 ml, 95% CI
− 59.27 to − 17.12, P o 0.01, respectively). Declines in hemoglobin and hematocrit values after CS were both significantly less in TXA
group than in control group. The difference of postpartum hemorrhage rate was statistically significant between groups (risk ratio
(RR) 0.57, 95% CI 0.37 to 0.89, P = 0.01). The need for blood transfusion was significantly less in TXA group than control group (RR
0.23, 95% CI 0.10 to 0.57, P o0.01).
CONCLUSION: Our results demonstrate that TXA offers an advantage over no TXA in reducing blood loss during and after CS.
Journal of Perinatology advance online publication, 30 July 2015; doi:10.1038/jp.2015.93

INTRODUCTION different scales.10–19 However, the results have reached no

The rate of cesarean section (CS) has increased in both developed
and developing countries in recent decades.1 It was estimated in
2010 that CS rate was 32% in United States2 and 42% in China,3
which are both considerably higher than World Health Organiza-
tion’s recommended proportion of 10 to 15%. Delivery by CS is
associated with more complications than vaginal delivery. One of
the most common complications is postpartum hemorrhage (PPH)
being regarded as the leading cause of preventable maternal
mortality worldwide.4 Besides, PPH is related with the increased
rate of blood transfusion5 and the occurrence of serious anemia.6
Therefore, it is needed to explore effective approaches to reduce
blood loss during and after CS.
Tranexamic acid (TXA), a synthetic derivative of the amino acid
lysine, has been used in the treatment of bleeding for many
years. It expressed its antifibrinolytic effect via the reversible
blockade of the lysine binding sites on plasminogen molecules
and the inhibition of plasminogen converting to plasmin.7
Numerous studies have demonstrated that TXA had a vital role
in preventing or decreasing intra- and postoperative blood loss
in various surgeries including coronary artery bypass, arthro-
plasty, orthognathic surgery and liver transplantation.8 In 2004,
Gai et al.9 first reported a multi-center, randomized controlled
trial (RCT), showing a significant reduction in total blood loss and
postpartum blood loss when TXA was administrated immediately
before CS. To determine the clinical efficacy of TXA in decreasing
bleeding during and after cesarean delivery, other obstetricians
have continuously carried out the corresponding studies on
consensus.
Therefore, we aimed to conduct a comprehensive meta-analysis
of published RCTs to demonstrate the hypothesis that TXA could
significantly reduce blood loss during and after CS when
compared with no TXA.
METHODS
We performed this study in accordance with the Statement of Preferred
Reporting Items for Systematic Reviews and Meta-Analyses.20
Search strategy
The electronic databases utilized in our literature search included MEDLINE
(PubMed), EMBASE, Cochrane Central Register of Controlled Trials and Web
of Science. The following MeSH terms and text words were used without
language restrictions: ‘tranexamic acid’, ‘antifibrinolyticagent’, ‘cesarean’,
‘caesarean’, ‘blood loss’ and ‘hemorrhage’. The latest search was conducted
on 13 June 2015. Two authors independently reviewed the titles and
abstracts identified in the search. All references cited in the articles were
also searched by hand to identify additional publications.
Study selection
Only RCTs that compared intravenous TXA with no TXA before CS for
intraoperative and postpartum blood loss were eligible for inclusion. If two
or more trials from the same institution were identified, the most recent or
the most informative was selected, unless they were reports from different
time periods or if the data of overlapping patients could be subtracted.
Retrospective studies, reviews and case reports were excluded. If it was

Department of Obstetrics and Gynecology, Shengli Oilfield Central Hospital, Binzhou Medical University, Dongying, China. Correspondence: Dr H-M Yin, Department of Obstetrics
and Gynecology, Shengli Oilfield Central Hospital, Binzhou Medical University, 31 Jinan Road, Dongying 257034, Shandong, China.
E-mail: yinhongmei2014@sina.com
Received 18 January 2015; revised 19 June 2015; accepted 22 June 2015
 Tranexamic acid and blood loss in cesarean section
H-Y Wang et al
2
impossible to calculate the quantity of blood loss from the published
results then the assessed study was also excluded.
Data extraction
The data were extracted independently by the two reviews. Any
discrepancies between the two authors were resolved by discussion or
arbitration by a third author. The following information was extracted from
each trial: first author’s last name, publication year, country, study interval,
patient characteristics (mean age, weight and gestational age), the doses
of TXA, blood collection periods, blood loss measurement, the volumes of
intraoperative and postpartum blood loss, the declines in hemoglobin and
hematocrit values after CS, the incidence of PPH, blood loss 41000 ml, and
blood transfusion.
Quality assessment
The methodological quality of the included RCTs was assessed and
calculated using the Jadad scale,21 which evaluates a study in terms of the
description of randomization, double-blinding and withdrawals or drop-
outs. According to the scale, the studies were divided into a high-quality
group (score ⩾ 3) and a low-quality group (scoreo 3).

Statistical analysis
86 reports identified through The outcomes were pooled as estimate of the overall effect for the meta-
analysis conducted using the statistical software Review Manage, version
database searching
5.1.0 (The Cochrane Collaboration, 2011). Analysis of continuous variables
was done by calculating the mean difference (MD) with the corresponding
95% confidence interval (CI) in inverse variance method. If studies reported
66 reports excluded by reviewing continuous data as median and/or range values, s.d. was calculated using
of title and abstract statistical algorithms by Hozo et al.22 For dichotomous variables, the risk
ratio (RR) for each study was aggregated in Mantel–Haenszel (M–H)
method to obtain a pooled RR with a corresponding 95% CI. Assessment of
20 reports retrieved for more statistical heterogeneity among studies was done by the Cochran’s Q-test
detailed evaluation and I2 statistics. For Q-test, Po 0.1 was considered statistically significant.23
As previously described,24 if there was a significant heterogeneity, the
random effects model would be used; otherwise, the fixed-effect model
8 articles excluded would be chosen. Funnel plot was constructed to detect the possibility of
4 reviews publication bias.25 A symmetrical inverted funnel in the plot indicates the
absence of this possibility, whereas an asymmetrical shape represents the
1 communication presence of publication bias. The visual asymmetry of the funnel plot was
3 articles employed patients tested by Egger’s regression with Po0.1 considered as significant.26
to undergo vaginal delivery

RESULTS
12 potential trials included in
Trial flow
meta-analysis A total of 86 citations were identified from literature searches.
After selection, 12 studies met the criteria for inclusion in the
meta-analysis. Of these, one RCT by Shakur et al.27 provided no
1 trial excluded due to no data for outcome data for our analysis and was excluded. Therefore, 11
analysis RCTs9–19 were eligible for final inclusion with a total of 2531
women in our analysis. The flow diagram in Figure 1 details the
selection process.
11 trials included in final
meta-analysis Study characteristics
The major study characteristics are summarized in Table 1. All 11
Figure 1. Flow diagram of search. trials were carried out in 6 countries and published in

Table 1. Study characteristics

Author Year Country Study interval Cases Age (years) Weight (kg) Gestational age Doses Jadad
(weeks) of TXA Score

Study Control Study Control Study Control Study Control

9
Gai et al. 2004 China NA 91 89 (N) 29.71 29.75 72.67 71.33 38.80 38.67 1g 3
Gohel et al.10 2007 India 2004–2005 50 50 (N) 24.30 24.89 49.71 49.64 38.85 38.64 1g 3
Sekhavat et al.11 2009 Iran 2004–2005 45 45 (P) 26.2 27.1 NA NA NA NA 1g 3
Gungorduk et al.13 2011 Turkey 2009 330 330 (P) 26.3 26.6 NA NA 38.7 38.8 1g 4
Movafegh et al.12 2011 Iran 2009–2010 50 50 (P) 27.0 27.6 NA NA 38.9 39.0 10 mg kg − 1 5
Sentürk et al.18 2013 Turkey 2010 101 122 (P) 30.20 29.22 75.53 74.22 NA NA 1g 4
Xu et al.19 2013 China 2008–2011 88 86 (P) 26.7 27.1 65.3 66.5 38.7 38.8 10 mg kg − 1 4
Shahid et al.16 2013 Pakistan 2009–2011 38 36 (P) 24.18 24.89 66.58 64.50 38.32 38.47 1g 5
Halder et al.14 2013 India NA 50 50 (N) 26.06 26.04 68.30 68.38 NA NA 1g 2
Abdel-Aleem et al.17 2013 Egypt 2010–2011 373 367 (N) 26.34 26.62 NA NA 39.32 39.31 1g 3
Goswami et al.15 2013 India 2009–2011 30 30 (P) 23.6 24.3 57.1 57.7 NA NA 10 mg kg − 1 4
30 22.8 58.0 15 mg kg − 1
Abbreviations: N, no treatment; NA, not applicable; P, placebo; TXA, tranexamic acid.

Journal of Perinatology (2015), 1 – 8 © 2015 Nature America, Inc.

 Tranexamic acid and blood loss in cesarean section
H-Y Wang et al
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Table 2. Blood collection periods and blood loss measurement in the included studies

Author Blood collection periods Blood loss measurement

Gai et al.9 From PD to the end of CS, and from the end of CS ((Weight of used materials + unused materials − weight of all
to 2-h postpartum materials before CS)/1.05) + the volume included in the suction
container after placental delivery
Gohel et al.10 From PD to the end of CS, and from the end of CS (Weight of used materials in both the periods − weight of the
to 2-h postpartum materials before CS) + the volume included in the suction
container after placental delivery; the pads used from the end of
CS to 2-h postpartum were separately weighed
Sekhavat et al.11 From the end of CS to 2 h postpartum (Weight of used materials − weight of materials before used)/1.05;
the soaked, specially designed operating sheet used from the
end of CS to 2-h postpartum were separately weighed
Gungorduk et al.13 NA EBV × (preoperative hematocrit − 48-h postpartum hematocrit)/
preoperative hematocrit, where EBV in ml = the woman’s weight
in kg × 85
Movafegh et al.12 From PD to the end of CS, and from the end of CS ((Weight of bloody materials − weight of dry materials)/1.05) + the
to 2-h postpartum volume included in the suction container after placental delivery;
the soaked pads and gauze used from the end of CS to 2-h
postpartum were separately weighed
Sentürk et al.18 From the start of skin incision to before entrance (Wet weight of materials − dry weight of materials)/1.05; the pad
of the intrauterine cavity, from uterine repair to closure used in the service room was separately weighed
of the skin, and during the patients in service room
Xu et al.19 From PD to the end of CS, and from the end of CS ((Weight of used materials + unused materials − weight of all
to 2-h postpartum materials before CS)/1.05) + the volume included in the suction
container after placental delivery
Shahid et al.16 From PD to the end of CS, and from the end of CS (Weight of used materials in both the periods − weight of the
to 2-h postpartum materials before CS) + the volume included in the suction
container after placental delivery; the pads used from the end of
CS to 2-h postpartum were separately weighed
Halder et al.14 From PD to the end of CS, and from the end of CS (Weight of used materials in both the periods − weight of the
to 2-d postpartum materials before CS) + the volume included in the suction
container after placental delivery; the pads used from the end of
CS to 2-h postpartum were separately weighed
Abdel-Aleem During CS, and from the end of CS to 2-h postpartum ((Weight of wet materials − weight of dry materials) × 0.9) + the
et al.17 volume included in the suction container; a calibrated plastic
drape used from the end of CS to 2-h postpartum were
separately weighed
Goswami et al.15 NA (Weight of materials after CS − weight of materials before
CS) + the volume included in the suction container after placental
delivery; the pads used from the end of CS to 24-h postpartum
were separately weighed
Abbreviations: CS, cesarean section; EBV, estimated blood volume; NA, not applicable; PD, placental delivery.

Figure 2. Forest plot of total blood loss. Diamond represents the overall estimate of the meta-analysis. The width of diamond represents 95%
confidence interval (CI).

English-language journals between 2004 and 2013. A total of 1276
women in this analysis received intravenous administration of TXA
and 1255 received nothing or placebo as control. Demographic
factors in two groups were similar with no statistically significant
difference. Eight studies9–11,13,14,16–18 applied TXA in the dose of
1g and two studies12,19 in the dose of 10 mg kg − 1, whereas the
study conducted by Goswami et al.15 used two doses (10 mg kg − 1
and 15 mg kg − 1) of TXA in anemic parturients undergoing CS. The
periods of blood collection and the measurement of blood loss in
the included studies were presented in Table 2. In total, no serious

© 2015 Nature America, Inc. Journal of Perinatology (2015), 1 – 8

 Tranexamic acid and blood loss in cesarean section
H-Y Wang et al
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adverse events associated with the use of TXA were recorded

Abbreviations: CI, confidence interval; HG, heterogeneity; IV, inverse variance; MD, mean difference; M–H, Mantel–Haenszel; NA, not applicable; PPH, postpartum hemorrhage; RR, risk ratio. Fixed indicates fixed-
P-value

o0.01
o0.01
0.07
o0.01
0.01
o0.01
o0.01
o0.01
0.01
o0.01
o0.01
o0.01
o0.01
0.02
0.01
0.03
o0.01
except two cases of deep vein thrombosis in each group reported
by Xu et al.19

Quality assessment

I2 (%)
With regard to methodological quality of included RCTs in this

NA
98
98
97
98
99
90

99
99
91
97
98
80
85
0
0
0
analysis, 10 trials9–13,15–19 described in detail the method of
randomization. Six trials12,13,15–19 described as double-blind,
whereas only two12,16 of them have appropriate double-blinding
method. Withdrawals or dropouts were described in all trials.

P-value for HG
Sample size calculations were adequately described in five

o 0.01
o 0.01
o 0.01
o 0.01
o 0.01
o 0.01

o 0.01
o 0.01
o 0.01
o 0.01
o 0.01
0.03
0.01
0.47
0.37
0.84
studies.12,13,15,17,19 According to Jadad scoring system, all of the

NA
included RCTs were regarded as better quality trials except the
trial by Halder et al.14 (Table 1).

Total blood loss

Nine included RCTs reported the volumes of total blood loss

(−303.68, − 228.32)
(−207.09, − 76.14)
(−224.34, − 59.27)

(−220.38, − 66.35)
(−276.01, − 37.08)
(−173.97, − 46.73)
during and after CS. Of these, eight RCTs9–13,16–19 showed a

(−59.27, − 17.12)

(−92.03, − 21.97)
(−54.67, − 7.45)
(−291.71, 9.25)

(−1.30, − 0.45)
(−1.65, − 0.34)
(−0.93, − 0.34)
(−3.42, −0.23)
significant reduction in total blood loss when TXA was admini-

Effect estimate

(0.37, 0.89)
(0.20, 0.92)
(0.10, 0.57)
strated intravenously, as compared with no TXA. One RCT by
Halder et al.,14 however, found no significant difference in total
bleeding between two groups. When nine RCTs were pooled in
this analysis, the volume of total blood loss was significantly less in

− 0.87
− 0.99
− 0.64
− 1.82
0.57
0.43
0.23
− 141.61
− 141.81
− 141.23
− 143.36
− 156.54
− 110.35
− 266.00
− 38.20
− 31.06
− 57.00
TXA group than control group by 141.61 ml (95% CI − 207.09 to
− 76.14, P o 0.01; Figure 2). Subgroup analysis for the dose of 1g
further showed a significant reduction in total blood loss in study
group (MD − 141.81 ml, 95% CI − 224.34 to − 59.27, Po 0.01),
whereas for the dose of 10 mg kg − 1 found that the reduction did
not approach statistical significance (MD − 141.23 ml, 95% CI
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
MD (IV, random, 95% CI)
RR (M–H, fixed, 95% CI)
RR (M–H, fixed, 95% CI)
RR (M–H, fixed, 95% CI)
− 291.71 to 9.25, P = 0.07). Heterogeneities across studies were
statistically significant (P o 0.1; Table 3).
Statistical method

Intraoperative blood loss

Information about intraoperative blood loss was described in
seven trials. A significant difference of intraoperative bleeding
between two groups was observed in five trials.10,12,15–17 The
other two trials9,19 reported that such difference was insignificant.
Our pooled results revealed that TXA could significantly reduce
intraoperative blood loss when compared with control group (MD
Cases

60
2351
2077
274
1458
1094
334

1458
1184
274
1427
1153
274
313
1104
1400
1047
− 143.36 ml, 95% CI − 220.38 to − 66.35, P o 0.01; Figure 3).
Besides, subgroup analyses for the doses of 1g (MD − 156.54 ml,
Summary estimates of meta-analysis and subgroup analysis

95% CI − 276.01 to − 37.08, P = 0.01), 10 mg kg − 1 (MD − 110.35 ml,

95% CI − 173.97 to − 46.73, P o 0.01), and 15 mg kg − 1 (MD
Seven9,10,13,14,16-18

Seven9,10,12,15-17,19

− 266.00 ml, 95% CI − 303.68 to − 228.32, Po 0.01) all demon-

Nine9,10,12-14,16-19

Seven9-12,16,17,19

strated the significant effect of TXA on decreasing intraoperative

Six11,12,14,17-19
No. of studies

Four11,14,17,18

Four10,15,17,19

Four13,15,16,18
Four9,10,16,17
Three12,15,19

Five9-11,16,17

effect model and random indicates random-effect model.

blood loss. Heterogeneities across studies were statistically

Two12,19

Two12,19

Two12,19
Two11,18

Two13,17

significant (Po 0.1; Table 3). A sensitivity analysis for the subgroup
One15

of dose of 10 mg kg − 1 was performed, and the result was

unchanged (MD − 145.57 ml, 95% CI − 167.29 to − 123.86,
Po 0.01) with no heterogeneity across studies (I2 = 0%, P = 0.72).
Incidence of blood loss 41000 ml

Postpartum blood loss

In our analysis, there were seven studies9–12,16,17,19 providing
Intraoperative blood loss (ml)

Hemoglobin decline (g dl − 1)

the data of postpartum blood loss. These trials all exhibited a

Postpartum blood loss (ml)

significant reduction in postpartum bleeding in study group

Dose of 10 mg kg − 1

Dose of 10 mg kg − 1
Dose of 15 mg kg − 1

Dose of 10 mg kg − 1

Dose of 10 mg kg − 1

except the trial by Shahid et al.16 Our meta-analytic pooling

Total blood loss (ml)

Hematocrit decline

showed a significant reduction of postpartum blood loss by

Blood transfusion
Incidence of PPH

38.20 ml in TXA group (95% CI − 59.27 to − 17.12, P o 0.01;

Dose of 1 g

Dose of 1 g

Dose of 1 g

Dose of 1 g

Figure 4). Subgroup analysis for the doses of 1 g (MD − 31.06 ml,
95% CI − 54.67 to − 7.45, P = 0.01) and 10 mg kg − 1 (MD − 57.00 ml,
Outcome

95% CI − 92.03 to − 21.97, Po 0.01) both revealed that this

Table 3.

reduction was statistically significant. Statistical heterogeneities

across studies were significant (P o0.1; Table 3).

Journal of Perinatology (2015), 1 – 8 © 2015 Nature America, Inc.


Hemoglobin
Six trials11,12,14,17–19 reported the decline in hemoglobin values after
CS. The pooling results of our meta-analysis (MD − 0.87 g dl − 1,
95% CI − 1.30 to − 0.45, Po0.01; Figure 5) and subgroup analysis
(doses of 1g (MD − 0.99 g dl − 1, 95% CI − 1.65 to − 0.34, Po0.01)
and 10 mg kg − 1 (MD − 0.64 g dl − 1, 95% CI − 1.93 to − 0.34,
Po0.01)) all showed that the decline in hemoglobin was
significantly less in study group than in control group. Statistical
heterogeneities across studies were significant (Po0.1; Table 3).
Hematocrit
Only two studies11,18 in this analysis provided the data regarding
the decline in hematocrit level following CS. Both individual
trials and meta-analysis suggested significantly less decline in
Tranexamic acid and blood loss in cesarean section
H-Y Wang et al
5
hematocrit level in TXA group (MD − 1.82, 95% CI − 3.42 to − 0.23,
P = 0.02; Figure 6). Statistical heterogeneities across studies were
significant (P o0.1; Table 3).
Incidence of PPH
Five trials9,10,17,19 reported the information of PPH rate. Four of
these trials defined PPH as postpartum bleeding ⩾ 500 ml,
whereas the trial by Gai et al.9 used a value of 400 ml as threshold.
Therefore, the data in the latter trial were not included in statistical
analysis. Overall, 4.38% (25/571) parturients experienced PPH in
study group and 8.07% (43/533) in control group. Our meta-
analysis illustrated a significant difference of PPH rate between
groups (RR 0.57, 95% CI 0.37 to 0.89, P = 0.01; Figure 7). No
statistical heterogeneity across studies was found (I2 = 0%, P = 0.47;
Table 3).

Figure 3. Forest plot of intraoperative blood loss. Diamond represents the overall estimate of the meta-analysis. The width of diamond
represents 95% confidence interval (CI).

Figure 4. Forest plot of postpartum blood loss. Diamond represents the overall estimate of the meta-analysis. The width of diamond
represents 95% confidence interval (CI).

Figure 5. Forest plot of hemoglobin decline. Diamond represents the overall estimate of the meta-analysis. The width of diamond represents
95% confidence interval (CI).

© 2015 Nature America, Inc. Journal of Perinatology (2015), 1 – 8

 Tranexamic acid and blood loss in cesarean section
H-Y Wang et al
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Incidence of excessive bleeding
There were two trials13,17 in our analysis reported the incidence of
blood loss 41000 ml. Overall, 1.28% (9/703) patients sustained
such excessive bleeding in study group and 3.01% (21/697) in
control group. Our meta-analysis showed that the difference of
this outcome between groups was statistically significant (RR 0.43,
95% CI 0.20 to 0.92, P = 0.03; Figure 8) with no intergroup
heterogeneity (I2 = 0%, P = 0.37; Table 3).
Blood transfusion
Four trials13,15,16,18 provided the data about the need for blood
transfusion. Overall, 0.95% (5/529) patients in study group needed
blood transfusion comparing with 4.05% (21/518) patients in
control group. A significant difference of blood transfusion
between groups was observed in our meta-analysis (RR 0.23,
95% CI 0.10 to 0.57, P o 0.01; Figure 9). There was no
heterogeneity across studies (I2 = 0%, P = 0.84; Table 3).
Publication bias
Visual inspection of the funnel plot showed asymmetry
(Figure 10). Nevertheless, the Egger’s regression analysis, con-
ducted using STATA Version 12.0, demonstrated that the visual
Figure 6. Forest plot of hematocrit decline. Diamond represents the overall estimate of the meta-analysis. The width of diamond represents
95% confidence interval (CI).
Figure 7. Forest plot of incidence of postpartum hemorrhage. Diamond represents the overall estimate of the meta-analysis. The width of
diamond represents 95% confidence interval (CI).
Figure 8. Forest plot of incidence of blood loss 41000 ml. Diamond represents the overall estimate of the meta-analysis. The width of
diamond represents 95% confidence interval (CI).
Journal of Perinatology (2015), 1 – 8
asymmetry was not significant (95% CI of intercept − 16.27 to 8.01,
P = 0.45).
DISCUSSION
Our meta-analysis of 11 RCTs showed that TXA, given before the
start of CS, could significantly decrease blood loss during and after
CS with less hematological change when compared with no TXA.
Moreover, our results found that TXA was associated with lower
incidence of PPH and less need for blood transfusion.
During placental separation, fibrinogen and fibrinare rapidly
degraded, whereas plasminogen activators and fibrin degradation
products increase due to activation of the fibrinolytic system,
which can last 6 to 10-h postpartum, resulting in more bleeding.28
In order to weaken the activity of the fibrinolytic system, TXA was
chosen reasonably to reduce blood loss in obstetrical surgeries. In
2001, Yang et al.29 employed 400 women with term singleton
pregnancy, vertex presentation and spontaneous delivery to
investigate the efficacy of TXA for preventing PPH. They have
found that TXA in the dose of 1 g or 0.5 g could significantly
reduce the postpartum blood loss as compared with no treatment.
Later, a RCT9 conducted in China recruited 180 primiparas to
undergo CS, 91 of whom received 1 g of TXA intravenously. In that
© 2015 Nature America, Inc.

Figure 9. Forest plot of blood transfusion. Diamond represents the overall estimate of the meta-analysis. The width of diamond represents
95% confidence interval (CI).
Figure 10. Funnel plot for publication bias. Square represents each
trial. The plot shows visual asymmetry.
trial, a significant reduction in total blood loss from placental
delivery to 2-h postpartum was observed in treatment group (352
vs 439 ml). However, a different study result has been reported
from a trial14 conducted in India, describing no significant
difference of total blood loss between two groups (990 vs
1004 ml) with a lower Jadad score (2 points). Our meta-analysis, in
accordance with the results of other recent trials,16–19 supported
the notion of intravenous injection of TXA having a significant role
in the reduction of total blood loss during and after CS.
Reducing operative blood loss would lower the risks and costs
associated with blood transfusion. Blood is a scarce resource but
even when blood is available, it can transmit potentially fatal viral
infections. Although two trials9,19 conducted in China did not
show any differences regarding intraoperative blood loss between
the groups and explained as the time of TXA administration, our
meta-analysis did demonstrate the superiority of intravenous TXA
in decreasing blood loss during CS and the need for blood
transfusion.
Many previous studies have found that the volume of
postpartum bleeding could be effectively decreased by TXA in
comparison to no TXA treatment.9–12,16,17,19 Nevertheless, a trial16
completed recently in Pakistan has not shown such satisfying
outcome regarding postpartum bleeding with 36 ml in study
group and 44 ml in control group (P40.05). Our findings in this
analysis were in complete agreement with those studies support-
ing the advantage of TXA in reducing postpartum blood loss as
compared with no TXA. Moreover, our results showed that the
incidence of PPH was reduced significantly by intravenous TXA. In
addition, the number of patients who sustained an excessive
bleeding (41000 ml) was significantly less in our TXA group than
© 2015 Nature America, Inc.
Tranexamic acid and blood loss in cesarean section
H-Y Wang et al
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in control group. These evidences raised the possibility that TXA
may be an effective treatment for PPH, which accounts for about
166 000 maternal deaths every year, with an average interval from
onset of bleeding to death of 2 to 4 h.30 To demonstrate this
hypothesis, Ducloy-Bouthors et al.31 randomized 144 women with
PPH 4800 ml following vaginal delivery to receive either TXA
(n = 72) or not (n = 72). The study has found that blood loss from
enrollment to 6 h later was significantly less by 48 ml in study
group compared with control group. A larger scale trial, the
WOMAN trial (World Maternal Antifibrinolytic Trial), aiming to
enroll 15 000 women with PPH around the world, is currently
being undertaken.27 The trial will provide a stronger reliable
evidence for the application of TXA in patients with PPH.
It was a concern that the volume of blood loss estimated during
CS would be affected by amnion fluid.32 Thus, in order to obtain
more objective data, the declines of hemoglobin and hematocrit
values after CS were noted and recorded in some trials.11,12,14,17–19
In accordance with the results of these studies, our meta-analysis
showed a significantly less decline in hemoglobin and hematocrit
levels in study group, which may be considered as a clinical effect
of TXA on stabilizing the hematological change in the postpartum
period.
It should be noted that our study involved three doses of TXA.
Eight trials9–11,13,14,16–18 used TXA in dose of 1g, two12,19 in dose of
10 mg kg − 1 and one15 in doses of 10 mg kg − 1 and 15 mg kg − 1
with a dose-dependent relationship demonstrated. Hence, we
performed subgroup analyses and found that the results were
similar to our meta-analyses although one exception presented
(Table 3). Given a much larger sample size, the potential difference
of related outcome would be detected between the groups.
Regrettably, we did not show the dose-dependent relationship of
TXA due to the study design of each trial. Perhaps future studies
focusing on this issue may provide more evidences to address this
concern.
With regard to adverse effects of TXA therapy, most events are
mild and transient. Although the incidence of thrombosis during
pregnancy is 5 to 6 times higher than that in nonpregnant
population,33 thromboembolic events resulted from the use of
TXA have been reported rarely. The included trial by Xu et al.19
described that two women receiving TXA suffered from deep vein
thrombosis, whereas another two women receiving no TXA
experienced the same complication. None of the other included
trials reported thromboembolic events or other serious side
effects, which showed strong evidence for the safety of TXA in
preventing or decreasing bleeding in pregnant woman. Despite
these findings, it should be highly cautious to use TXA in women
with history of thrombosis or other risk factors.
The main limitation of the present meta-analysis is the
heterogeneity across studies. Clinical heterogeneity involves
preparation and administration of the medication, surgical
experience of the obstetricians, blood collection periods and
Journal of Perinatology (2015), 1 – 8
 Tranexamic acid and blood loss in cesarean section
H-Y Wang et al
8
calculation of the quantity of blood. For example, most trials
measured blood loss from placental delivery to the end of CS and
from the end of CS to 2-h postpartum, whereas two trials17,18
designed the period early to the skin incision and one14 late to
2 days postpartum. The trial by Gungorduk et al.13 used the
difference of hematocrit values between before and 48 h after CS
to estimate blood loss, which was different from the other trials
using the difference of the weight of materials and the volume
included in the suction container for calculation. The control
group in this analysis involves placebo treatment and no
treatment. Theoretically, these two designs should be analyzed
separately. However, we could not do this due to the limited
studies in this review. As a result, these potential variations might
have influenced the results of this study. Assessment of statistical
heterogeneity by the Q-test and I2 statistics showed a significant
heterogeneity among studies that could not be eliminated by
sensitivity analysis except one outcome. Consequently, most
pooled outcome measures were determined using a random-
effect model, which has taken those heterogeneities into account.
Another limitation is potential publication bias on the basis of
visual asymmetry of the funnel plot. The majority of included
studies were conducted in Asia, which may introduce selection
bias. This bias along with intergroup heterogeneity might have
contributed to asymmetry in the funnel plot. However, our
literature search was performed on several relevant databases
according to the standards of the Cochrane Collaboration with no
language restrictions. The study selection and data extraction
were done independently by two authors. Moreover, the Egger’s
regression analysis provided no evidences for the presence of
publication bias. Despite these, the results of our study need to be
interpreted with caution.
CONCLUSION
In summary, our meta-analysis supports the use of TXA before CS
for prevention of blood loss during and after CS compared with no
TXA. It can safely decrease the incidence of PPH without
increasing the risk of thrombosis. Given the significant intergroup
heterogeneity in this study, further randomized, larger scale trials
are needed to provide more evidences to demonstrate the
efficacy of TXA in preventing blood loss during and after CS.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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