ABOUBAKR ELNASHAR

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
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3. 1. INTRODUCTION
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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)
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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)
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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

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 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

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 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

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 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
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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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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.
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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
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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.

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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.

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 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

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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)

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ACOG, 2017

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Risk factors and the associated levels of risk for PPH (RCOG, 2016)

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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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