Comparison of the Effect of Intravenous Tranexamic Acid and Sublingual Misoprostol on Reducing Bleeding After Cesarean Section: A Double-Blind Randomized Clinical Trial

  • Hamideh Pakniat
  • Venus Chegini
  • Azarmidokht Shojaei
  • Marzieh Beigom KhezriEmail author
  • Iman Ansari
Original Article



To evaluate the effects of intravenous tranexamic acid (TA) and sublingual misoprostol on reducing bleeding after cesarean section.


One hundred and fifty-eight participants with term pregnancies scheduled for cesarean section were randomly divided into two groups. In M group, two sublingual misoprostol pills (400 mg) were administrated, immediately after the delivery. In TA group, ten minutes before skin incision, TA ampoule (1 g) was injected. In both groups, immediately after the delivery, 20 units of oxytocin in 1 L ringer lactate with speed of 1000 CC/h was injected. At the end of the operation, the amount of bleeding was measured based on the number of small and large gauzes, the blood in the suction container and the difference of patient’s hemoglobin before and 24 h after surgery.


Hemoglobin level reduction in the TA group was higher than the M group (− 2.45 ± 0.84 vs − 2.14 ± 1.38 g/dL) (P < 0.001). Furthermore, number of used gauze and blood suction in the TA group was significantly higher compared to sublingual misoprostol (4.67 ± 1.34 vs 3.25 ± 1.31 and 260.25 ± 79.06 vs 193.94 ± 104.79 cc, respectively) (P < 0.001). Mean blood pressure during the entire duration of surgery in the TA group decreased significantly as compared to the M group (P < 0.001).


Total bleeding was significantly lower in sublingual misoprostol as compared to the tranexamic acid group. Furthermore, in misoprostol group hemodynamic variables were stabilized greater than tranexamic acid group.

Registration Number



Tranexamic acid Misoprostol Postpartum hemorrhage Cesarean section 



This study was supported in part by Kowsar Research Center of Kowsar Hospital, Qazvin University of Medical Sciences. We gratefully acknowledge the Zahra Sadat Mohammadi for assistance with statistical analysis.

Compliance with Ethical Standards

Conflict of interest

The authors declared no conflict of interest. The authors have no financial conflict of interest to declare.

Ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the 1975 Declaration of Helsinki, as revised in 2008 (5).

Informed consent

Informed consent was obtained from all patients for being included in the study.


  1. 1.
    Gebhardt GS, Fawcus S, Moodley J, et al. Maternal death and caesarean section in South Africa: results from the 2011–2013 Saving Mothers report of the National Committee for Confidential Enquiries into Maternal Deaths. S Afr Med J. 2015;105:287–91. Scholar
  2. 2.
    Edwards HM. Aetiology and treatment of severe postpartum haemorrhage. Dan Med J. 2018;65(3).Google Scholar
  3. 3.
    Saccone G, Caissutti C, Ciardulli A, et al. Uterine massage for preventing postpartum hemorrhage at cesarean delivery: which evidence? Eur J Obstet Gynecol Reprod Biol. 2018;223:64–7. Scholar
  4. 4.
    Mannaerts D, Van der Veeken L, Coppejans H, et al. Adverse effects of carbetocin versus oxytocin in the prevention of postpartum haemorrhage after caesarean section: a randomized controlled trial. J Pregnancy. 2018;2018:1374150. Scholar
  5. 5.
    Pattinson RC. Reducing direct causes of maternal death. S Afr J Obstet Gynaecol. 2013;19(3):59–60.Google Scholar
  6. 6.
    Begley CM, Gyte GM, Devane D, et al. Active versus expectant management for women in the third stage of labour. Cochrane Database Syst Rev. 2011. Scholar
  7. 7.
    Dyer RA, Butwick AJ, Carvalho B. Oxytocin for labour and caesarean delivery: implications for the anaesthesiologist. Curr Opin Anaesthesiol. 2011;24(3):255–61. Scholar
  8. 8.
    Ducloy-Bouthors AS, Jeanpierre E, Saidi I, et al. TRAnexamic acid in hemorrhagic CESarean section (TRACES) randomized placebo controlled dose-ranging pharmacobiological ancillary trial: study protocol for a randomized controlled trial. Trials. 2018;19(1):149. Scholar
  9. 9.
    Levy JH, Dutton RP, Hemphill JC, et al. Multidisciplinary approach to the challenge of hemostasis. Anesth Analg. 2010;110(2):354–64. Scholar
  10. 10.
    CRASH-2 trial collaborators, Shakur H, Roberts I, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23–32. Scholar
  11. 11.
    Alam A, Choi S. Prophylactic use of tranexamic acid for postpartum bleeding outcomes: a systematic review and meta-analysis of randomized controlled trials. Transfus Med Rev. 2015;29(4):231–41. Scholar
  12. 12.
    Bouthors AS, Hennart B, Jeanpierre E, et al. Therapeutic and pharmaco-biological, dose-ranging multicentre trial to determine the optimal dose of TRAnexamic acid to reduce blood loss in haemorrhagic CESarean delivery (TRACES): study protocol for a randomised, double-blind, placebo-controlled trial. Trials. 2018;19(1):148. Scholar
  13. 13.
    Sentilhes L, Lasocki S, Ducloy-Bouthors AS, et al. Tranexamic acid for the prevention and treatment of postpartum haemorrhage. Br J Anaesth. 2015;114(4):576–87. Scholar
  14. 14.
    Novikova N, Hofmeyr GJ, Cluver C. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database Syst Rev. 2015. Scholar
  15. 15.
    Abdel-Aleem H, Alhusaini TK, Abdel-Aleem MA, et al. Effectiveness of tranexamic acid on blood loss in patients undergoing elective cesarean section: randomized clinical trial. J Matern Fetal Neonatal Med. 2013;26(17):1705–9. Scholar
  16. 16.
    Sentürk MB, Cakmak Y, Yildiz G, et al. Tranexamic acid for cesarean section: a double-blind, placebo-controlled, randomized clinical trial. Arch Gynecol Obstet. 2013;287(4):641–5. Scholar
  17. 17.
    Conde-Agudelo A, Nieto A, Rosas-Bermudez A, et al. Misoprostol to reduce intraoperative and postoperative hemorrhage during cesarean delivery: a systematic review and metaanalysis. Am J Obstet Gynecol. 2013;209(1):40.e1–17. Scholar
  18. 18.
    Tunçalp Ö, Hofmeyr GJ, Gülmezoglu AM. Prostaglandins for preventing postpartum haemorrhage. Cochrane Database Syst Rev. 2012. Scholar
  19. 19.
    Pakniat H, Khezri MB. The effect of combined oxytocin-misoprostol versus oxytocin and misoprostol alone in reducing blood loss at cesarean delivery: a prospective randomized double-blind study. J Obstet Gynaecol India. 2015;65(6):376–81. Scholar
  20. 20.
    Fazel MR, Samimi M, Fakharian E. A comparison of rectal misoprostol and intravenous oxytocin on hemorrhage and homeostatic changes during cesarean section. Middle East J Anesthesiol. 2013;22(1):41–6.PubMedGoogle Scholar
  21. 21.
    Sahhaf F, Abbasalizadeh S, Ghojazadeh M, et al. Comparison effect of intravenous tranexamic acid and misoprostol for postpartum haemorrhage. Niger Med J. 2014;55(4):348–53. Scholar
  22. 22.
    Al-Sawaf A, El-Mazny A, Shohayeb A. A randomised controlled trial of sublingual misoprostol and intramuscular oxytocin for prevention of postpartum haemorrhage. J Obstet Gynaecol. 2013;33(3):277–9. Scholar
  23. 23.
    Ugwu IA, Oluwasola TA, Enabor OO, et al. Randomized controlled trial comparing 200 μg and 400 μg sublingual misoprostol for prevention of primary postpartum hemorrhage. Int J Gynaecol Obstet. 2016;133(2):173–7. Scholar
  24. 24.
    Othman ER, Fayez MF, El Aal DE, et al. Sublingual misoprostol versus intravenous oxytocin in reducing bleeding during and after cesarean delivery: a randomized clinical trial. Taiwan J Obstet Gynecol. 2016;55(6):791–5. Scholar
  25. 25.
    Atukunda EC, Siedner MJ, Obua C, et al. Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage in Uganda: a double-blind randomized non-inferiority trial. PLoS Med. 2014;11(11):e1001752. Scholar
  26. 26.
    Chaudhuri P, Majumdar A. Sublingual misoprostol as an adjunct to oxytocin during cesarean delivery in women at risk of postpartum hemorrhage. Int J Gynaecol Obstet. 2015;128(1):48–52. Scholar
  27. 27.
    Ugwu IA, Enabor OO, Adeyemi AB, et al. Sublingual misoprostol to decrease blood loss after caesarean delivery: a randomised controlled trial. J Obstet Gynaecol. 2014;34(5):407–11. Scholar
  28. 28.
    Okonofua FE, Ogu RN, Akuse JT, et al. Assessment of sublingual misoprostol as first-line treatment for primary post-partum hemorrhage: results of a multicenter trial. J Obstet Gynaecol Res. 2014;40(3):718–22. Scholar

Copyright information

© Federation of Obstetric & Gynecological Societies of India 2018

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyQazvin University of Medical SciencesQazvinIran
  2. 2.Faculty of MedicineQazvin University of Medical SciencesQazvinIran
  3. 3.Department of AnesthesiologyQazvin University of Medical SciencesQazvinIran
  4. 4.Shahed UniversityTehranIran

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