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Tranexamic acid
for management of
Postpartum Haemorrhage
Prof. Aboubakr Elnashar
Benha university Hospital, Egypt
ABOUBAKR...
CONTENTS
1. INTRODUCTION
 PPH
 TA
2. TA FOR TREATMENT OF PPH
3. TA FOR PREVENTION OF PPH
 CONCLUSION
ABOUBAKR ELNASHAR
3
1. INTRODUCTION
ABOUBAKR ELNASHAR
PPH
Traditional definition
Blood loss ≥
500mL following VD, or
1000mL following CS.
(ACOG, 2006)
 An updated definiti...
For normal woman undergoing CS
Blood loss of 1000 mL
Common
Minimal effect on women’s health status.
For woman with s...
Postpartum:
Increased
D-dimer levels
fibrinolytic activity
Obs hge:
increased fibrinolytic activity
Placental disru...
TA
 Mechanism of action
Potent antifibrinolytic agent= Inhibition of fibrinolysis
blocking lysine binding sites on plas...
Normally, plasminogen binds with tissue plasminogen activator (tPA) to form plasmin.
This binding degrades fibrin into fi...
 Rationale TA administration
During delivery, when the placenta separates
Physiologic and haemostatic changes
1. Strong ...
 Half life: 2 hours
 Metabolized by kidney
 Routes of administration:
IV
Oral
Topical
 The peak of serum levels aft...
Widely uses in
O&G
Cardiac surgery
Oral surgery
Liver transplant
Urology
Effective and safe in reduce blood loss in...
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 bl...
ABOUBAKR ELNASHAR
 Safety and risks
1.Nausea and vomiting.
The most commonly reported adverse effect
2. At higher doses:
...
ABOUBAKR ELNASHAR
 Contraindications
1. Known hypersensitivity to TA
2. Significant renal impairment.
3. Active thromboti...
ABOUBAKR ELNASHAR
 Cost-effectiveness
 highly cost-effective in low- to middle-income
countries
 equally cost-effective...
2. TA FOR TREATMENT OF PPH
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR
WOMAN trial
20,060 woman with diagnosed PPH
193 hospitals in 21 countries
Significant decrease in death due to bleedin...
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR
WHO recommendation, 2017
Early use(within 3 h of birth) of IV TA
in addition to standard care
is recommended for women w...
TA should be used in all cases of PPH
regardless of whether the bleeding is due to
genital tract trauma or
other cause...
Cochrane SR, 2018
IV TA
reduces mortality due to bleeding in women with
primary PPH
irrespective of mode of birth
wit...
3. TA FOR PREVENTION OF PPH
I. According to route of delivery
II. According to risk for PPH
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR
I. According to Route of delivery
A. Prophylactic TA in vaginal delivery
 TRAAP trial 2018
(Sentilhes e...
ABOUBAKR ELNASHAR
 Prophylactic TA cannot be routinely recommended in
vaginal delivery
1. In spite of statistically signi...
ABOUBAKR ELNASHAR
B. Prophylactic TA in CS
 Wang et al 2015
 11 RCTs
 before elective CS
 TXA intervention significant...
ABOUBAKR ELNASHAR
 Simonazzi et al, 2016
 9 RCT, 2365 CS, including multiple pregnancies,
elective and selective CS
 TA...
 Li et al, 2017 SR
25 articles
4747 participants
TA
Reduced blood loss
ABOUBAKR ELNASHAR
TotalPostoperativeIntra oper...
ABOUBAKR ELNASHAR
II. According to risk of PPH
 In the prevention of PPH TA should be considered in
addition to oxytocin
...
ABOUBAKR ELNASHAR
ACOG, 2017
ABOUBAKR ELNASHAR
Risk factors and the associated levels of risk for PPH (RCOG, 2016)
ABOUBAKR ELNASHAR
CONCLUSIONS
 In the treatment of PPH
 1 g of IV TA should be initiated within 3 h of birth
 In preven...
ABOUBAKR ELNASHAR
You can get this lecture and 404 lectures
from:
1.My scientific page on Face book:
Aboubakr Elnashar Le...
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TRANXAMIC ACID IN MANAGEMENT OF POSTPARTUM HEMORRHAGE

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TRANXAMIC ACID IN MANAGEMENT OF POSTPARTUM HEMORRHAGE

  1. 1. Tranexamic acid for management of Postpartum Haemorrhage Prof. Aboubakr Elnashar Benha university Hospital, Egypt ABOUBAKR ELNASHAR
  2. 2. CONTENTS 1. INTRODUCTION  PPH  TA 2. TA FOR TREATMENT OF PPH 3. TA FOR PREVENTION OF PPH  CONCLUSION ABOUBAKR ELNASHAR 3
  3. 3. 1. INTRODUCTION ABOUBAKR ELNASHAR
  4. 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. ABOUBAKR ELNASHAR
  5. 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. ABOUBAKR ELNASHAR
  6. 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. 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. 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. ABOUBAKR ELNASHAR
  9. 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. ABOUBAKR ELNASHAR
  10. 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) ABOUBAKR ELNASHAR
  11. 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) ABOUBAKR ELNASHAR
  12. 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. 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. 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. 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. 16. 2. TA FOR TREATMENT OF PPH ABOUBAKR ELNASHAR
  17. 17. ABOUBAKR ELNASHAR
  18. 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 ABOUBAKR ELNASHAR
  19. 19. ABOUBAKR ELNASHAR
  20. 20. ABOUBAKR ELNASHAR
  21. 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. 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 ABOUBAKR ELNASHAR
  23. 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. 24. 3. TA FOR PREVENTION OF PPH I. According to route of delivery II. According to risk for PPH ABOUBAKR ELNASHAR
  25. 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. 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. 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. 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. 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. 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. 31. ABOUBAKR ELNASHAR ACOG, 2017
  32. 32. ABOUBAKR ELNASHAR Risk factors and the associated levels of risk for PPH (RCOG, 2016)
  33. 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. 34. ABOUBAKR ELNASHAR You can get this lecture and 404 lectures from: 1.My scientific page on Face book: Aboubakr Elnashar Lectures. https://www.facebook.com/groups/2277 44884091351/ 2.Slide share web site 3. elnashar53@hotmail.com 4. My clinic, 3 Althawra St. Almansura
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