This document discusses the use of tranexamic acid (TA) for the management of postpartum hemorrhage (PPH). It summarizes that TA reduces bleeding by inhibiting fibrinolysis and promoting clot formation. For treatment of diagnosed PPH, early administration of IV TA within 3 hours of birth reduces mortality from bleeding without increasing thrombotic risks. For prevention, IV TA may reduce bleeding for those at higher risk of PPH, such as cesarean deliveries, but its routine use after vaginal births requires more research.

1. Tranexamic acid
for management of
Postpartum Haemorrhage
Prof. Aboubakr Elnashar
Benha university Hospital, Egypt
ABOUBAKR ELNASHAR

2. CONTENTS
1. INTRODUCTION
 PPH
 TA
2. TA FOR TREATMENT OF PPH
3. TA FOR PREVENTION OF PPH
 CONCLUSION
ABOUBAKR ELNASHAR
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3. 1. INTRODUCTION
ABOUBAKR ELNASHAR

4. PPH
Traditional definition
Blood loss ≥
500mL following VD, or
1000mL following CS.
(ACOG, 2006)
 An updated definition
 Cumulative blood loss≥
 1000 mL OR
 accompanied by SorS of hypovolemia within 24 h
after the birth process regardless of the route of
delivery.
(ACOG, 2017)
Any blood loss sufficient to compromise haemodynamic stability.
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5. For normal woman undergoing CS
Blood loss of 1000 mL
Common
Minimal effect on women’s health status.
For woman with severe anemia or CVD undergoing VD
Blood loss of as little as 200mL
may be
life-threatening
need additional intervention.
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6. Postpartum:
Increased
D-dimer levels
fibrinolytic activity
Obs hge:
increased fibrinolytic activity
Placental disruption:
increase in tPA
Trauma: Endothelial injury or hypoperfusion
Increased
tPA
fibrin degradation products
(Pacheco. Obstet Gynecol. 2017)
ABOUBAKR ELNASHAR

7. TA
 Mechanism of action
Potent antifibrinolytic agent= Inhibition of fibrinolysis
blocking lysine binding sites on plasminogen
molecules
Inhibits
activation of plasminogen to plasmin.
ability of plasmin to form fibrin degradation
productions
clot breakdown (fibrinolysis):
 bleeding is reduced.
(Pacheco. Obstet Gynecol. 2017)
ABOUBAKR ELNASHAR

8. Normally, plasminogen binds with tissue plasminogen activator (tPA) to form plasmin.
This binding degrades fibrin into fibrin degradation products and leads to clot lysis.
TA binds to the lysine binding site on plasminogen. This new conformation blocks
plasmin binding to fibrin. Fibrin strands are not broken, and a clot persists to slow
bleeding.
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9.  Rationale TA administration
During delivery, when the placenta separates
Physiologic and haemostatic changes
1. Strong myometrial contractions
2. Increased platelet activity
Massive release of coagulation factors:
increase fibrinolytic activity
Oxytocin administration:
enhances the first mechanism
TA administration
counter the latter: facilitate the haemostatic
process.
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10.  Half life: 2 hours
 Metabolized by kidney
 Routes of administration:
IV
Oral
Topical
 The peak of serum levels after IV infusion:
within minutes in nonpregnant patients.
(Jerath et al, 2018)
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11. Widely uses in
O&G
Cardiac surgery
Oral surgery
Liver transplant
Urology
Effective and safe in reduce blood loss in
Menorrhagia
Hysterectomy
Myomectomy.
(Naoulou et al, 2013Topsoee et al, 2014Shaabanet al, 2015)
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12. ABOUBAKR ELNASHAR
Prophylaxis Treatment
Dose  1 g or
 10 mg/kg IV
 1 g in 10 mL IV over 10 m
 2nd dose of 1 g IV if bleeding
 continues after 30 m or
 restarts within 24 h of
completing the first dose.
(WHO, 2018)
Timing  10 to 20 m before
skin incision OR
 At the time of
umbilical cord clamp
{avoid any placental
transfer}
Within 3h of delivery
Dose & timing in management of PHH

13. ABOUBAKR ELNASHAR
 Safety and risks
1.Nausea and vomiting.
The most commonly reported adverse effect
2. At higher doses:
 Other gastrointestinal
 Seizures
 These doses are not recommended for obstetrics
Risk of thrombotic tendency, Seizures
Renal complications: Not higher than controls
(Cochrane SR, 2018)
Rarely
 when administered before cord clamping
{TA cross the placenta}:
severe adverse neonatal effects

14. ABOUBAKR ELNASHAR
 Contraindications
1. Known hypersensitivity to TA
2. Significant renal impairment.
3. Active thrombotic disease:
DVT, pulmonary embolism, and cerebral thrombosis.
4. Significant history or risk for VTE
unless it is possible to simultaneously administer anticoagulation.
5. Rare contraindications:
 disturbances of color vision before or during administration of TXA
or
 active subarachnoid hemorrhage

15. ABOUBAKR ELNASHAR
 Cost-effectiveness
 highly cost-effective in low- to middle-income
countries
 equally cost-effective in other countries with a high
burden of maternal mortality due to PPH.
(Li et al, 2018)

16. 2. TA FOR TREATMENT OF PPH
ABOUBAKR ELNASHAR

17. ABOUBAKR ELNASHAR

18. WOMAN trial
20,060 woman with diagnosed PPH
193 hospitals in 21 countries
Significant decrease in death due to bleeding
Hysterectomy rates did not change
Death from all causes did not decrease
No increase in adverse outcomes with TA
( VTE)
 Effects of early tranexamic acid administration on mortality, hysterectomy, and
other morbidities in women with postpartum hemorrhage (WOMAN):
An international, randomized, double-blind, placebo controlled trial.
Lancet , 2017
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20. ABOUBAKR ELNASHAR

21. WHO recommendation, 2017
Early use(within 3 h of birth) of IV TA
in addition to standard care
is recommended for women with clinically
diagnosed PPH following
vaginal birth or
CS.
(Strong recommendation, moderate quality of evidence)
TA administration beyond 3 h
does not confer any clinical benefit
harm, albeit not statistically significant for women with PPH.
No support for use of TA more than 3 h after birth.
ABOUBAKR ELNASHAR

22. TA should be used in all cases of PPH
regardless of whether the bleeding is due to
genital tract trauma or
other causes.
The use of TA should be avoided in
clear contraindication to antifibrinolytic therapy
known thromboembolic event during pregnancy
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23. Cochrane SR, 2018
IV TA
reduces mortality due to bleeding in women with
primary PPH
irrespective of mode of birth
without increasing the risk of thromboembolic
events
effective if given as early as possible.
Alternative routes to IV administration need to be
investigated
ABOUBAKR ELNASHAR

24. 3. TA FOR PREVENTION OF PPH
I. According to route of delivery
II. According to risk for PPH
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25. ABOUBAKR ELNASHAR
I. According to Route of delivery
A. Prophylactic TA in vaginal delivery
 TRAAP trial 2018
(Sentilhes et al, 2018)
 Tranexamic Acid for the Prevention of Postpartum
Hemorrhage After Vaginal Delivery
 Multicenter, double-blind, RCT
 4,070 singleton gestations ≥35 w
 1 g within 2 min after vaginal delivery
 Lower incidence of PPH
(6.6% vs 8.8%, P = 0.01),
reduced need for uterotonics
(7.3% vs 9.7%, P =0.003)

26. ABOUBAKR ELNASHAR
 Prophylactic TA cannot be routinely recommended in
vaginal delivery
1. In spite of statistically significant decrease in blood
loss
 this may not convey clinical significance in terms of
 transfusion rates and
 maternal comorbidity from severe hemorrhage.
2. Limited high-quality evidence
Larger, well designed RCTs are required to help
formulate guideline recommendations.

27. ABOUBAKR ELNASHAR
B. Prophylactic TA in CS
 Wang et al 2015
 11 RCTs
 before elective CS
 TXA intervention significantly reduced
 intraoperative blood loss during and after cesarean
delivery
 without an increase in thromboembolic events;
 reduction was similar for both 1 g dosing and
weight-based TXA dosing regimens.

28. ABOUBAKR ELNASHAR
 Simonazzi et al, 2016
 9 RCT, 2365 CS, including multiple pregnancies,
elective and selective CS
 TA compared with controls. had significantly less
 Blood loss
(−160.27; 95% CI, −224.63 to−95.92)
 Drop in hemoglobin
(−0.61 g/dL;95% CI, −1.04 to −0.18)
 PPH
 Need for uterotonics
(4.2% vs 7.3%; RR, 0.54; 95% CI,0.36–0.81).
 Blood transfusion
(1.9% vs 5.7%; RR, 0.33; 95% CI, 0.19–0.58).
 Heterogeneity in
 TA dosing & timing
 Methods for measuring blood loss

29.  Li et al, 2017 SR
25 articles
4747 participants
TA
Reduced blood loss
ABOUBAKR ELNASHAR
TotalPostoperativeIntra operative
155 ml36 ml140 mlCS
85 ml41ml23 mlVD
Lower rate of
PPH
Blood transfusions.
No increased risk of DVT
Minor side effects were more common

30. ABOUBAKR ELNASHAR
II. According to risk of PPH
 In the prevention of PPH TA should be considered in
addition to oxytocin
 At the time of CS in women who are at risk for
PPH
(RCOG Green -top Guideline, 2016)
 Before both vaginal and CS in patients at higher
risk for PPH
(Ahmadzia et al, 2018)
 Prediction of PPH is based mostly on clinical risk
factors.
(James et al, 2012)

31. ABOUBAKR ELNASHAR
ACOG, 2017

32. ABOUBAKR ELNASHAR
Risk factors and the associated levels of risk for PPH (RCOG, 2016)

33. ABOUBAKR ELNASHAR
CONCLUSIONS
 In the treatment of PPH
 1 g of IV TA should be initiated within 3 h of birth
 In prevention of PPH
 1g of IV TA after cord clamping of both vaginal and
CD should be considered in patients at higher risk
for PPH.

34. ABOUBAKR ELNASHAR
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