Am J Perinatol 2015; 32(05): 469-474
DOI: 10.1055/s-0034-1390347
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Tranexamic Acid to Reduce Postpartum Hemorrhage: A MANDATE Systematic Review and Analyses of Impact on Maternal Mortality

Elizabeth M. McClure
1   Department of Social, Statistical and Environmental Health Sciences, Research Triangle Institute, Durham, North Carolina
,
Bonnie Jones
1   Department of Social, Statistical and Environmental Health Sciences, Research Triangle Institute, Durham, North Carolina
,
Doris J. Rouse
1   Department of Social, Statistical and Environmental Health Sciences, Research Triangle Institute, Durham, North Carolina
,
Jennifer B. Griffin
1   Department of Social, Statistical and Environmental Health Sciences, Research Triangle Institute, Durham, North Carolina
,
Beena D. Kamath-Rayne
2   Department of Pediatrics, Perinatal Institute, Cincinnati Children's Hospital, Cincinnati, Ohio
,
Allan Downs
3   Department of Research Computing Division, Research Triangle Institute, Durham, North Carolina
,
Robert L. Goldenberg
4   Department of Obstetrics and Gynecology, Columbia University, New York
› Author Affiliations
Further Information

Publication History

15 March 2014

05 August 2014

Publication Date:
07 October 2014 (online)

Abstract

Objective Postpartum hemorrhage (PPH) is a major cause of maternal mortality, with almost 300,000 cases and ∼72,000 PPH deaths annually in sub-Saharan Africa. Novel prevention methods practical in community settings are required. Tranexamic acid, a drug to reduce bleeding during surgical cases including postpartum bleeding, is potentially suitable for community settings. Thus, we sought to determine the impact of tranexamic acid on PPH-related maternal mortality in sub-Saharan Africa.

Study Design We created a mathematical model to determine the impact of interventions on PPH-related maternal mortality. The model was populated with baseline birth rates and mortality estimates based on a review of current interventions for PPH in sub-Saharan Africa. Based on a systematic review of literature on tranexamic acid, we assumed 30% efficacy of tranexamic acid to reduce PPH; the model assessed prophylactic and treatment tranexamic acid use, for deliveries at homes, clinics, and hospitals.

Results With tranexamic acid only in the hospitals, less than 2% of the PPH mortality would be reduced. However, if tranexamic acid were available in the home and clinic settings for PPH prophylaxis and treatment, a nearly 30% reduction (nearly 22,000 deaths per year) in PPH mortality is possible.

Conclusion These analyses point to the importance of preventive and treatment interventions compatible with home and clinic use, especially for sub-Saharan Africa, where the majority of births occur at home or community health clinics. Given its feasibility to be given in the home, tranexamic acid has potential to save many lives.

 
  • References

  • 1 Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet 2006; 367 (9516) 1066-1074
  • 2 Beltman J, VAN DEN Akker T, VAN Lonkhuijzen L, Schmidt A, Chidakwani R, VAN Roosmalen J. Beyond maternal mortality: obstetric hemorrhage in a Malawian district. Acta Obstet Gynecol Scand 2011; 90 (12) 1423-1427
  • 3 Darmstadt GL, Lee AC, Cousens S , et al. 60 Million non-facility births: who can deliver in community settings to reduce intrapartum-related deaths?. Int J Gynaecol Obstet 2009; 107 (Suppl. 01) S89-S112
  • 4 Roberts I, Ker K. Tranexamic acid for postpartum bleeding. Int J Gynaecol Obstet 2011; 115 (3) 220-221
  • 5 Shakur H, Elbourne D, Gülmezoglu M , et al. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials 2010; 11: 40
  • 6 Shakur H, Roberts I, Bautista R , et al; CRASH-2 trial collaborators. 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
  • 7 Roberts I, Shakur H, Afolabi A , et al; CRASH-2 collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet 2011; 377 (9771) 1096-1101 , e1–e2
  • 8 World Health Organization. Summary of the report of the 18th meeting of the WHO Expert Committee on the Selection and Use of Essential Medicines. March 21–25, 2011; Accra, Ghana. Available at: http://www.who.int/selection_medicines/committees/expert/18/en/index.html
  • 9 Guerriero C, Cairns J, Perel P, Shakur H, Roberts I ; CRASH 2 trial collaborators. Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial. PLoS ONE 2011; 6 (5) e18987
  • 10 Freeman EW, Lukes A, VanDrie D, Mabey RG, Gersten J, Adomako TL. A dose-response study of a novel, oral tranexamic formulation for heavy menstrual bleeding. Am J Obstet Gynecol 2011; 205 (4) e1-e7
  • 11 Ducloy-Bouthors AS, Jude B, Duhamel A , et al; EXADELI Study Group. High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Crit Care 2011; 15 (2) R117
  • 12 de Guzman R, Polykratis IA, Sondeen JL, Darlington DN, Cap AP, Dubick MA. Stability of tranexamic acid after 12-week storage at temperatures from -20°c to 50°c. Prehosp Emerg Care 2013; 17 (3) 394-400
  • 13 Gungorduk K, Asıcıoğlu O, Yıldırım G, Ark C, Tekirdağ AI, Besımoglu 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. Am J Perinatol 2013; 30 (5) 407-413
  • 14 Movafegh A, Eslamian L, Dorabadi A. Effect of intravenous tranexamic acid administration on blood loss during and after cesarean delivery. Int J Gynaecol Obstet 2011; 115 (3) 224-226
  • 15 Peitsidis P, Kadir RA. Antifibrinolytic therapy with tranexamic acid in pregnancy and postpartum. Expert Opin Pharmacother 2011; 12 (4) 503-516
  • 16 Sekhavat L, Tabatabaii A, Dalili M, Farajkhoda T, Tafti AD. Efficacy of tranexamic acid in reducing blood loss after cesarean section. J Matern Fetal Neonatal Med 2009; 22 (1) 72-75
  • 17 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 (3) 463-468
  • 18 Shahid A, Khan A. Tranexamic acid in decreasing blood loss during and after caesarean section. J Coll Physicians Surg Pak 2013; 23 (7) 459-462
  • 19 Abdel-Aleem H, Alhusaini TK, Abdel-Aleem MA, Menoufy M, Gülmezoglu AM. Effectiveness of tranexamic acid on blood loss in patients undergoing elective cesarean section: randomized clinical trial. J Matern Fetal Neonatal Med 2013; 26 (17) 1705-1709
  • 20 Sentürk 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 (4) 641-645
  • 21 McClure EM, Rouse DJ, Macguire ER , et al. The MANDATE model for evaluating interventions to reduce postpartum hemorrhage. Int J Gynaecol Obstet 2013; 121 (1) 5-9
  • 22 Rudan I, Gibson J, Kapiriri L , et al; Child Health and Nutrition Research Initiative (CHNRI). Setting priorities in global child health research investments: assessment of principles and practice. Croat Med J 2007; 48 (5) 595-604
  • 23 Goudar SS, Carlo WA, McClure EM , et al. The Maternal and Newborn Health Registry Study of the Global Network for Women's and Children's Health Research. Int J Gynaecol Obstet 2012; 118 (3) 190-193
  • 24 Klufio CA, Amoa AB, Kariwiga G. Primary postpartum haemorrhage: causes, aetiological risk factors, prevention and management. P N G Med J 1995; 38 (2) 133-149
  • 25 Dildy III GA. Postpartum hemorrhage: new management options. Clin Obstet Gynecol 2002; 45 (2) 330-344
  • 26 Rath WH. Postpartum hemorrhage—update on problems of definitions and diagnosis. Acta Obstet Gynecol Scand 2011; 90 (5) 421-428
  • 27 Flandermeyer D, Stanton C, Armbruster D. Uterotonic use at home births in low-income countries: a literature review. Int J Gynaecol Obstet 2010; 108 (3) 269-275
  • 28 MANDATE model; Available at: http://mnhtech.org (Accessed November 15, 2013)
  • 29 Novikova N, Hofmeyr GJ. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database Syst Rev 2010; (7) CD007872
  • 30 Ferrer P, Roberts I, Sydenham E, Blackhall K, Shakur H. Anti-fibrinolytic agents in post partum haemorrhage: a systematic review. BMC Pregnancy Childbirth 2009; 9: 29
  • 31 Gai MY, Wu LF, Su QF, Tatsumoto K. Clinical observation of blood loss reduced by tranexamic acid during and after caesarian section: a multi-center, randomized trial. Eur J Obstet Gynecol Reprod Biol 2004; 112 (2) 154-157
  • 32 Cook L, Roberts I ; WOMAN Trial Collaborators. Post-partum haemorrhage and the WOMAN trial. Int J Epidemiol 2010; 39 (4) 949-950
  • 33 As AK, Hagen P, Webb JB ; AK. Tranexamic acid in the management of postpartum haemorrhage. Br J Obstet Gynaecol 1996; 103 (12) 1250-1251
  • 34 Cook L, Roberts I ; WOMAN Trial Collaborators. Post-partum haemorrhage and the WOMAN trial. Int J Epidemiol 2010; 39 (4) 949-950
  • 35 de Lange NM, Lancé MD, de Groot R, Beckers EA, Henskens YM, Scheepers HC. Obstetric hemorrhage and coagulation: an update. Thromboelastography, thromboelastometry, and conventional coagulation tests in the diagnosis and prediction of postpartum hemorrhage. Obstet Gynecol Surv 2012; 67 (7) 426-435
  • 36 Onwuemene O, Green D, Keith L. Postpartum hemorrhage management in 2012: predicting the future. Int J Gynaecol Obstet 2012; 119 (1) 3-5
  • 37 Bonnet MP, Basso O. Prohemostatic interventions in obstetric hemorrhage. Semin Thromb Hemost 2012; 38 (3) 259-264
  • 38 Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs 1999; 57 (6) 1005-1032
  • 39 Sapire KE. A study of bleeding patterns with two injectable contraceptives given postpartum and the effect of two non-hormonal treatments. Adv Contracept 1991; 7 (4) 379-387
  • 40 Astedt B. Clinical pharmacology of tranexamic acid. Scand J Gastroenterol Suppl 1987; 137: 22-25
  • 41 Kapungu CT, Mensah-Homiah J, Akosah E , et al; Ghana PPH Study Group. A community-based continuum of care model for the prevention of postpartum hemorrhage in rural Ghana. Int J Gynaecol Obstet 2013; 120 (2) 156-159