Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1016/j.bjane.2022.08.002
Brazilian Journal of Anesthesiology
Systematic Review

Analysis of the efficacy of prophylactic tranexamic acid in preventing postpartum bleeding: systematic review with meta-analysis of randomized clinical trials

Análise da eficácia do ácido tranexâmico profilático na prevenção do sangramento pós-parto: revisão sistemática com metanálise de ensaios clínicos randomizados

Ivo de C. Assis, Catia S. Govêia, Denismar B. Miranda, Rafael S. Ferreira, Luiza G.C. Riccio

Downloads: 3
Views: 658

Abstract

Background
Postpartum Hemorrhage (PPH) is one of the main causes of maternal mortality, mainly in the poorest regions of the world, drawing attention to the need for strategies for preventing it. This study aims to evaluate the efficacy of prophylactic administration of Tranexamic Acid (TXA) in decreasing blood loss in pregnant women in delivery, preventing PPH.

Methods
Systematic review of randomized clinical trials. We searched for publications in PubMed, EMBASE and Cochrane Library databases, with the uniterms “postpartum, puerperal hemorrhage” and “tranexamic acid”, published between January of 2004 and January of 2020. The eligibility criteria were trials published in English with pregnant women assessed during and after vaginal or cesarean delivery about the effect of prophylactic use of TXA on bleeding volume. The random-effects model was applied with the DerSimonian-Laird test and the Mean Difference (MD) was calculated for continuous variables together with each 95% CI. This systematic review was previously registered in the PROSPERO platform under the registration n° CRD42020187393.

Results
Of the 630 results, 16 trials were selected, including one with two different doses, performing a total of 6731 patients. The intervention group received a TXA dose that varied between 10 mg.kg−1 and 1g (no weight calculation). The TXA use was considered a protective factor for bleeding (MD: -131.07; 95% CI: -170.00 to -92.78; p = 0.000) and hemoglobin variation (MD: -0.417; 95% CI: -0.633 to -0.202; p = 0.000). In the subgroup analysis related to the cesarean pathway, the effect of TXA was even greater.

Conclusion
The prophylactic use of tranexamic acid is effective in reducing the post-partum bleeding volume.

PROSPERO registration ID
CRD42020187393.

Keywords

Postpartum hemorrhage;  Prophylaxis;  Tranexamic acid  

Resumo

Introdução

A Hemorragia Pós-Parto (HPP) é uma das principais causas de mortalidade materna, principalmente nas regiões mais pobres do mundo, chamando a atenção para a necessidade de estratégias para preveni-la. Este estudo tem como objetivo avaliar a eficácia da administração profilática de Ácido Tranexâmico (TXA) na diminuição da perda sanguínea em gestantes no parto, prevenindo a HPP.

Métodos

Revisão sistemática de ensaios clínicos randomizados. Buscamos publicações nas bases de dados PubMed, EMBASE e Cochrane Library, com os unitermos “postpartum, puerperal hemorrhage” e “tranexamic acid”, publicadas entre janeiro de 2004 e janeiro de 2020. Os critérios de elegibilidade foram ensaios publicados em inglês com gestantes avaliadas durante e após parto vaginal ou cesariana sobre o efeito do uso profilático de TXA no volume de sangramento. O modelo de efeitos aleatórios foi aplicado com o teste DerSimonian-Laird e a Diferença Média (MD) foi calculada para variáveis contínuas juntamente com cada IC 95%. Esta revisão sistemática foi previamente registrada na plataforma PROSPERO sob o registro n° CRD42020187393.

Resultados

Dos 630 resultados, foram selecionados 16 ensaios, incluindo um com duas doses diferentes, realizando um total de 6.731 pacientes. O grupo intervenção recebeu uma dose de TXA que variou entre 10 mg.kg−1 e 1g (sem cálculo de peso). O uso de TXA foi considerado fator protetor para sangramento (DM: -131,07; IC 95%: -170,00 a -92,78; p = 0,000) e variação da hemoglobina (DM: -0,417; IC 95%: -0,633 a -0,202; p = 0,000). Na análise de subgrupo relacionada à via cesariana, o efeito do TXA foi ainda maior.

Conclusão

O uso profilático de ácido tranexâmico é eficaz na redução do volume de sangramento pós-parto.

ID de registro PROSPERO

CRD42020187393.

Palavras-chave

Hemorragia pós-parto; Profilaxia; Ácido tranexâmico  

References

1. Say L, Chou D, Gemmill A, et al. Global causes of maternal death: A WHO systematic analysis. Lancet Global Health. 2014;2:323−33.

2. Carroli G, Cuesta C, Abalos E, Gulmezoglu AM. Epidemiology of postpartum haemorrhage: a systematic review. Best Pract Res Clin Obstet Gynaecol. 2008;22:999−1012.

3. Sheldon WR, Blum J, Vogel JP, Souza JP, Gulmezoglu AM, Winik- € off B, et al. Postpartum haemorrhage management, risks, and maternal outcomes: findings from the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG. 2014;121(Suppl 1):5−13.

4. Anger H, Durocher J, Dabash R, Winikoff B. How well do postpartum blood loss and common definitions of postpartum hemorrhage correlate with postpartum anemia and fall in hemoglobin? PLoS ONE. 2019;14:1−13.

5. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: postpartum hemorrhage. Am Coll Obstet Gynecol. 2017;130:168−86.

6. Magann EF, Evans S, Hutchinson M, Collins R, Lanneau G, Morrison JC. Postpartum hemorrhage after cesarean delivery: An analysis of risk factors. South Med J. 2005;98:681−5.

7. Henry DA, Carless PA, Moxey AJ, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2007(4):CD001886.

8. Shakur H, Roberts I, Fawole B, et al. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017;389:2105−16.

9. Roberts I, Shakur H, Coats T, et al. The CRASH-2 trial: A randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technology Assessment. 2013;17:1−80.

10. Novikova N, Hofmeyr GJ, Cluver C. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database Syst Rev. 2015(6):CD007872.

11. Sentilhes L, Winer N, Azria E, et al. Tranexamic acid for the prevention of blood loss after vaginal delivery. N Engl J Med. 2018;379:731−42.

12. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

13. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan ‒ a web and mobile app for systematic reviews. Systematic Reviews. 2016;5(1):210.

14. Sterne JAC, Savovic J, Page MJ, et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ. 2019: 366.

15. Higgins JPT, Thompson SG. Quantifying heterogeneity in a metaanalysis. Statist Med. 2002;21:1539−58.

16. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088.

17. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629−34.

18. McMaster University 2020 (developed by Evidence Prime Inc.). GRADEpro GDT: GRADEpro Guideline Development Tool [Software] [Internet]. [cited 2020 Dec 21]. Available from: www.gradepro.org.

19. Brasil. Ministerio da Sa ude. Secretaria de Ci encia T e IEs- ^ trategicosD de C e Tecnologia. Methodological guideline: GRADE System − Manual graduation quality of evidence and strength of recommendation for decision making process in health.

20. Bhatia S, Deshpande H. Role of tranexamic acid in reducing blood loss during and after caesarean section. Med J Dr DY Patil University. 2015;8:21.

21. Sahu J, Mishra N. Role of intravenous tranexamic acid in reducing blood loss during caesarean section: Study at tribal-dominated area hospital in Chhattisgarh, India. J Obstet Gynaecol Res. 2019;45:841−8.

22. Abdel-Aleem H, Alhusaini TK, Abdel-Aleem MA, Menoufy M, Gulmezoglu AM. Effectiveness o € f tranexamic acid on blood loss in patients undergoing elective cesarean section: Randomized clinical trial. J Mat-Fetal Neonatal Med. 2013;26:1705−9.

23. Salas MT. A single-blinded randomized controlled trial on the effect of prophylactic intravenous administration of tranexamic acid on the reduction of blood loss during and after primary cesarean section ‒ Perinatal Medicine and General Obstetrics. J Obstet Gynaecol Res. 2017;43:20−55.

24. Ramani B, Nayak L. Intravenous 1-gram tranexamic acid for prevention of blood loss and blood transfusion during caesarean section: a randomized case control study. Inter J Reproduction Contraception Obstet Gynecol. 2014;3:366−9.

25. Gobbur V, Shiragur S, Jhanwar U, Tehalia M. Efficacy of tranexamic acid in reducing blood loss during lower segment caesarean section. Inter J Reproduction Contraception Obstet Gynecol. 2014;3:414−7.

26. Sadek S, Mahesan A, Ramadan H, Dad N, Movva V, Kanaan C. Prophylactic tranexamic acid usage in prevention of post-partum hemorrhage a prospective cohort study. Res Square. 2019: 1−13.

27. Gai MY, Wu LF, Su QF, Tatsumoto K. Clinical observation of blood loss reduced by tranexamic acid during and after cesarean section: A multi-center, randomized trial. Euro J Obstet Gynecol Reproductive Biol. 2004;112:154−7.

28. Yehia AH, Koleib MH, Abdelazim IA, Atik A. Tranexamic acid reduces blood loss during and after cesarean section: A double blinded, randomized, controlled trial. Asian Pacific J Reproduction. 2014;3:53−6.

29. Singh T, Burute SB, Deshpande HG, Jethani S, Ratwani K. Efficacy of tranexamic acid in decreasing blood loss during and after caesarean section: a randomized case control prospective study. J Evolution Med Dental Sci. 2014;3:2780−8.

30. Mayur G, Purvi Patel, Desai A. Efficacy of tranexamic acid in decreasing blood loss during and after cesarean section: a randamized case controlled prospective study. J Obstet Gynecol India. 2007;57:12.

31. Taj N, Fiardus A, Akhtar N, Chaudhary MH, Sarah Bajwa Z, et al. Efficacy of tranexamic acid in reducing blood loss during and after cesarean section. Rawal Med J. 2014;39:311−3.

32. Ray I, Bhattacharya R, Chakraborty S, Bagchi C, Mukhopadhyay S. Role of Intravenous Tranexamic Acid on Caesarean Blood Loss: A Prospective Randomised Study. J Obstet Gynecol India. 2016;66:347−52.

33. Sekhavat L, Tabatabaii A, Dalili M, Farajkhoda T, Tafti AD. Efficacy of tranexamic acid in reducing blood loss after cesarean section. J Maternal-Fetal Neonatal Med. 2009;22:72−5.

34. G B, MV A, Mittal S. Efficacy of prophylactic tranexamic acid in reducing blood loss during and after caesarean section. Inter J Reproduction Contraception Obstet Gynecol. 2016;39:2011−6.

35. Ahmed MR, Sayed Ahmed WA, Madny EH, Arafa AM, Said MM. Efficacy of tranexamic acid in decreasing blood loss in elective caesarean delivery. J Maternal-Fetal Neonatal Med. 2015;28:1014−8.

36. Sharma R, Najam R, Misra MK. Efficacy of Tranexamic Acid in Decreasing Blood Loss During and After Cesarean Section. Biomed Pharmacol J. 2011;4:231−5.

37. Roy P, Sujatha MS, Bhandiwad A, Biswas B. Role of Tranexamic Acid in Reducing Blood Loss in Vaginal Delivery. J Obstet Gynecol India. 2016;66:246−50.

38. Dhivya Lakshmi SJ, Abraham R. Role of prophylactic tranexamic acid in reducing blood loss during elective caesarean section: A randomized controlled study. J Clin Diagnost Res. 2016;10:17 −21.

39. Rashmi PS, Sudha TR, Prema P, Patil Rajashri, Vijayanath V. Role of Tranexamic acid in reducing blood loss during and after cesarean section: A randomized case control prospective study. J Med Res Practice. 2012;1:40−3.

40. Ayedi M, Jarraya A, Smaoui M, Zouari J, Smaoui L, Kolsi K. Effect of tranexamic acid on post-partum hemorrhage by uterine atony: A preliminary result of a randomized, placebocontrolled trial: 11AP4-7. Euro J Anaesthesiol. EJA. 2011;28:293.

41. Moradan S. Prophylactic effect of misoprostol versus tranexamic acid in conjunction with oxytocin in reduction of post-partum hemorrhage after cesarean section in: A randomized clinical trial. J Semnan University Med Sci. 2018;20:603−807.

42. Sujata N, Tobin R, Kaur R, Aneja A, Khanna M, Hanjoora VM. Randomized controlled trial of tranexamic acid among parturients at increased risk for postpartum hemorrhage undergoing cesarean delivery. Inter J Gynecol Obstet. 2016;133:312−5.

43. Movafegh A, Eslamian L, Dorabadi A. Effect of intravenous tranexamic acid administration on blood loss during and after cesarean delivery. Inter J Gynecol Obstet. 2011;115:224−6.

44. Ismail A, Abbas AM, Shahat. Mohamed A. Evaluation of subendometrial and intramyometrial blood flow after intravenous tranexamic acid for prevention of postpartum hemorrhage in vaginal delivery: a randomized controlled study. J Gynecol Res Obstet. 2017;3:046−50.

45. Abbas AM, Shady NW, Sallam HF. Bilateral uterine artery ligation plus intravenous tranexamic acid during cesarean delivery for placenta previa: a randomized double-blind controlled trial. J Gynecol Obstet Human Reproduction. 2019;48:115−9.

46. Senturk MB, Cakmak Y, Yildiz G, Yildiz P. Tranexamic acid for € cesarean section: A double-blind, placebo-controlled, randomized clinical trial. Arch Gynecol Obstet. 2013;287:641−5.

47. Gungorduk K, Ascoglu O, Yldrm G, Ark C, Tekirdag AI, Besmoglu B. Can intravenous injection of tranexamic acid be used in routine practice with active management of the third stage of labor in vaginal delivery? A randomized controlled study. Obstet Gynecol Surv. 2013;68:673−5.

48. Xu J, Gao W, Ju Y. Tranexamic acid for the prevention of postpartum hemorrhage after cesarean section: A double-blind randomization trial. Arch Gynecol Obstet. 2013;287:463−8.

49. Goswami U, Sarangi S, Gupta S, Babbar S. Comparative evaluation of two doses of tranexamic acid used prophylactically in anemic parturients for lower segment cesarean section: A double-blind randomized case control prospective trial. Saudi J Anaesth. 2013;7:427−31.

50. Shahid A, Khan A. Tranexamic acid in decreasing blood loss during and after caesarean section. Journal of the College of Physicians and Surgeons − Pakistan. JCPSP. 2013;23:459−62.

51. Ghosh A, Chaudhuri P, Muhuri B. Efficacy of intravenous tranexamic acid before cesarean section in preventing post partum hemorrhage- a prospective randomised double blind placebo controlled study. Inter J Biol Med Res. 2014;5:4461−4.

52. Maged AM, Helal OM, Elsherbini MM, et al. A randomized placebo-controlled trial of preoperative tranexamic acid among women undergoing elective cesarean delivery. Inter J Gynecol Obstet. 2015;131:265−8.

53. Mirghafourvand M, Mohammad-Alizadeh S, Abbasalizadeh F, Shirdel M. The effect of prophylactic intravenous tranexamic acid on blood loss after vaginal delivery in women at low risk of postpartum haemorrhage: A double-blind randomised controlled trial. Australian New Zealand J Obstet Gynaecol. 2015;55:53−8.

54. Milani F, Haryalchi K, Sharami SH, Atrkarroshan Z, Farzadi S. Prophylactic effect of tranexamic acid on hemorrhage during and after the cesarean section. Inter J Women’s Health Reproduction Scienc. 2019;7:74−8.

55. Shah P, Agrawal A, Chhetri S, Rijal P, Bhatta NK. Tranexamic acid in prevention of postpartum hemorrhage in elective cesarean section. Inter J Reproduction Contraception Obstet Gynecol. 2019;8:372.

56. Sujita A, Songthamwat S, Songthamwat M. Effectiveness of tranexamic acid for reducing postpartum blood loss in the first two hours after vaginal delivery: A randomised controlled trial. J Clin Diagnost Res. 2018;12:QC01−4.

57. Gungorduk K, Y{ld{r{m G, As{c{oglu O, Gungorduk O, Sudolmus S, Ark C. Efficacy of Intravenous tranexamic acid in reducing blood loss after elective cesarean section: a prospective, randomized, double-blind, placebo-controlled study. Am J Perinatol. 2011;28:233−40.

58. No GG. Prevention and management of postpartum haemorrhage. BJOG. 2017;124:e106−49.

59. Franchini M, Mengoli C, Cruciani M, et al. Safety and efficacy of tranexamic acid for prevention of obstetric haemorrhage: An updated systematic review and meta-analysis. Blood Transfusion. 2018;16:329−37.

60. Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines: 7. Rating the quality of evidence - Inconsistency. Journal of Clinical Epidemiology. 2011;64:1294−302.

6332f7eaa953956ac52b6073 rba Articles
Links & Downloads

Braz J Anesthesiol

Share this page
Page Sections