Updated WHO Recommendation on Tranexamic Acid for the Treatment of Postpartum Haemorrhage: Highlights and Key Messages from the World Health Organization’s 2017 Global Recommendation
Publication date: 2017
Updated WHO Recommendation on Tranexamic Acid for the Treatment of Postpartum Haemorrhage 1 Updated WHO Recommendation on Tranexamic Acid for the Treatment of Postpartum Haemorrhage Highlights and Key Messages from the World Health Organization’s 2017 Global Recommendation October 2017 www.mcsprogram.org Background Globally, nearly one-quarter of all maternal deaths are associated with PPH, and, in most low-income countries, PPH is the main cause of maternal mortality. The majority of PPH-associated deaths could be avoided by the use of prophylactic uterotonics during the third stage of labour and timely, appropriate management of PPH. Efforts to prevent and reduce maternal morbidity and mortality due to PPH can reduce the profound global inequities in maternal health outcomes. Health workers, managers, and policymakers need clear, up-to-date, evidence-based recommendations to inform maternal health policies, guidelines, education platforms, and programmes to strengthen maternal care and improve maternal health outcomes. TXA is a competitive inhibitor of plasminogen activation and can reduce bleeding by inhibiting the breakdown of fibrinogen and fibrin clots. Based on evidence for the benefit of TXA in improving trauma care outcomes, WHO’s recommendations for prevention and treatment of PPH issued in 2012 included a conditional recommendation to use TXA for treatment of PPH when uterotonics fail to control the bleeding or the bleeding is thought to be due to trauma.1 In 2017, the results of a large, randomized controlled trial, the World Maternal Antifibrinolytic Trial,2 were published and showed that early use of IV TXA (within 3 hours of birth and as soon as possible after onset Key Messages • The World Health Organization (WHO) recommends early use of intravenous tranexamic acid (TXA) within 3 hours of birth in addition to standard care for women with clinically diagnosed postpartum haemorrhage (PPH) following vaginal birth or caesarean section. • Administration of TXA should be considered as part of the standard PPH treatment package and be administered as soon as possible after onset of bleeding and within 3 hours of birth. TXA for PPH treatment should not be initiated more than 3 hours after birth. • TXA should be used in all cases of PPH, regardless of whether the bleeding is due to genital tract trauma or other causes. • TXA should be administered at a fixed dose of 1 g in 10 mL (100 mg/mL) IV at 1 mL per minute (i.e., administered over 10 minutes), with a second dose of 1 g IV if bleeding continues after 30 minutes. • TXA should be administered via an IV route only for treatment of PPH. Research on other routes of TXA administration is a priority. http://www.mcsprogram.org/ 2 Updated WHO Recommendation on Tranexamic Acid for the Treatment of Postpartum Haemorrhage of bleeding) reduces death due to bleeding in women with PPH, regardless of cause, and with no adverse maternal effects. In response to this new evidence, along with evidence from the forthcoming Cochrane systematic review on the efficacy of TXA for PPH3 and an individual participant data meta-analysis of 40,138 bleeding patients,4 WHO updated its 2012 PPH treatment recommendations to include use of TXA for treatment of PPH. This recommendation supersedes the recommendation on TXA in the existing 2012 WHO recommendations for the prevention and treatment of PPH.5 This brief presents highlights of the 2017 WHO TXA recommendation (see Table 1 below), including key changes to the pre-existing 2012 WHO TXA recommendation (Table 2), and explores policy and programme considerations for adopting and implementing the recommendation at the country level. The brief is intended to support policymakers, programme managers, educators, and providers to incorporate the 2017 WHO TXA recommendation for PPH treatment into existent country maternal health policies, education platforms, and programmes. It is important for country stakeholders to decide how to incorporate TXA into comprehensive PPH treatment algorithms and keep in mind the broader set of PPH intervention packages needed along the household-to-hospital care continuum for women who develop PPH, many of whom will not have prompt access to higher levels of care. Please see the full WHO 2017 TXA recommendation for PPH treatment for a detailed description of the methods used to develop the recommendation. Table 1. WHO 2017 recommendation on tranexamic acid for the treatment of postpartum haemorrhage WHO Recommendation Service Delivery and Clinical Guidance Early use of IV TXA (as early as possible after clinical diagnosis of PPH, and only within 3 hours of birth) in addition to standard care is recommended for women with clinically diagnosed PPH following vaginal birth or caesarean section. • Postpartum haemorrhage (PPH) is defined as estimated blood loss of more than 500 mL after a vaginal birth or 1,000 mL after caesarean section, or any blood loss sufficient to compromise haemodynamic stability. • Tranexamic acid (TXA) should be used in all cases of PPH, regardless of whether the bleeding is due to genital tract trauma or other causes. • TXA should be considered to be part of the standard comprehensive PPH treatment package, including medical (uterotonics), nonsurgical, and surgical interventions in accordance with WHO guidelines or adapted local PPH treatment protocols. • TXA should be readily available at all times in the delivery and postpartum areas of facilities providing emergency obstetric care. • TXA is relatively cheap in most contexts, easy to administer, often available in health care settings due to its use in trauma and surgery, has a shelf life of 3 years, and can be stored at room temperature (15–30 C) in many places.a • The reference point for the start of the 3-hour window for starting TXA administration is time of birth. If time of birth is unknown, the best estimate of time of birth should be used as the reference point. • Treatment delay in use of TXA appears to reduce benefit. The benefit appears to decrease by 10% for every 15-minute delay, with no benefit seen after 3 hours. • The point estimates of effect of TXA use beyond 3 hours on death for trauma6 and for PPH were both in the direction of harm, albeit not statistically significant for women with PPH. In view of this evidence, WHO recommends against the use of TXA more than 3 hours after birth. • TXA should be administered at a fixed dose of 1 g in 10 mL (100 mg/mL) IV at 1 mL per minute (i.e., administered over 10 minutes), with a second dose of 1 g IV if bleeding continues after 30 minutes or if bleeding restarts within 24 hours of completing the first dose. a Manufacturer instructions on storage and use should always be followed. Updated WHO Recommendation on Tranexamic Acid for the Treatment of Postpartum Haemorrhage 3 WHO Recommendation Service Delivery and Clinical Guidance • TXA should be administered slowly as an IV injection over 10 minutes, since bolus injection carries a potential risk of transient lowering of blood pressure. • TXA for injection may be mixed with most solutions for infusion, such as electrolyte solutions, carbohydrate solutions, amino acid solutions, and dextran solutions, and can be administered through the same IV cannula used for IV hydration or uterotonic administration. TXA should not be mixed with blood for transfusion, solutions containing penicillin, or mannitol.a • TXA should not be used in women with a clear contraindication to antifibrinolytic therapy, including TXA (e.g., a known thromboembolic event during pregnancy, history of coagulopathy, active intravascular clotting, or known hypersensitivity to TXA). Table 2. What is new about the use of tranexamic acid (TXA) to treat postpartum haemorrhage (PPH) in the 2017 WHO recommendation on TXA for PPH treatment? Indication Timing Dosing WHO 2012 TXA Recommendation Use of TXA is recommended for the treatment of PPH if oxytocin and other uterotonics fail to stop the bleeding or if it is thought that the bleeding may be partly due to trauma. For atonic uterus, use TXA if oxytocin and other uterotonics fail to stop the bleeding. IV (slowly): 1 g Repeat after 30 minutes if bleeding continues. WHO 2017 TXA Recommendation (updated) Use TXA in all cases of PPH, regardless of whether the bleeding is due to genital tract trauma or other causes. Use TXA within 3 hours and as early as possible after onset of PPH. Do not initiate TXA more than 3 hours after birth, unless being used for bleeding that restarts within 24 hours of completing the first dose (see dosing). Fixed dose of 1 g in 10 mL (100 mg/mL) IV at 1 mL per minute (i.e., administered over 10 minutes) Second dose of 1 g IV if bleeding continues after 30 minutes or if bleeding restarts within 24 hours of completing the first dose Policy and Programme Considerations The goals of the WHO 2017 recommendation on TXA for PPH treatment are to improve the quality of care for women with PPH and prevent maternal deaths due to PPH. Successful introduction of TXA as part of a standard PPH treatment package will require action on many fronts and engagement of multiple stakeholders across system levels, including policymakers, national and subnational ministry of health managers, professional societies, facility managers, facility health care workers, community leaders, health agents, and women and families. Below are considerations for country stakeholders incorporating the WHO 2017 TXA PPH treatment recommendation into national policy and country programmes. Photo by Jhpiego 4 Updated WHO Recommendation on Tranexamic Acid for the Treatment of Postpartum Haemorrhage National Policy Considerations • Policymakers should develop or update existing national PPH prevention and treatment guidelines, including PPH treatment algorithms, to incorporate TXA into the standard PPH treatment package. National policy should specify the levels of care for administration of TXA as part of PPH treatment, as well as the provider cadres that may administer TXA. Programme Implementation Considerations National Programme Managers: • Define and chart a plan for addressing the financial and programme requirements for implementing the WHO 2017 TXA PPH treatment recommendation in line with updated national policy. • Address status and needs for procurement, distribution, and storage of TXA and other PPH treatment medicines and supplies, including uterotonics. • National pre-service education directorates and institutions should review and update established curricula for PPH treatment (for relevant provider cadres), emphasizing competency-based approaches. • Review and revise (or develop) provider job aids and decision support tools to help providers acquire necessary skills and incorporate TXA into routine PPH treatment (e.g., pre- and in-service education/training, onsite job aids, and clinical algorithms). • Review national health management information system (HMIS) content and indicators relevant for PPH surveillance, prevention, and management, and prioritize PPH measures for monitoring at national, subnational, and facility levels (e.g., TXA stock-outs, PPH incidence, PPH case fatality, and PPH quality of care treatment measures, including TXA administration). The WHO standards for improving quality of maternal and newborn care in health facilities can be a useful resource and starting point for country stakeholders.7 • Review patient records for labour, childbirth, and postpartum care, and define areas of needed revision to capture essential clinical data points for provision of quality PPH clinical care and for calculation of quality measures to support quality improvement efforts (e.g., standardized place in record to record time of diagnosis of PPH, cause of PPH, time and dose of PPH treatments, PPH outcome, etc.). Regional/District Managers and Facility Health Workers: Facility Readiness to Administer TXA: • Per national protocol, ensure all facilities have copies of updated PPH treatment protocols, job aids, and decision support tools available for immediate use in labour, delivery, and postpartum areas. • Support a functioning supply chain to ensure 24/7 availability of TXA and IV supplies in labour, delivery, and postpartum areas of all facilities that provide emergency obstetric care. Health Worker Competencies and Behaviour Change: • Ensure competency-based in-service training and follow-up supportive supervision for all eligible providers to update PPH treatment skills, inclusive of TXA administration. • Address barriers and facilitators to provider behaviour change, including concerns and potential areas of resistance. Enlist respected clinician opinion leaders and champions. Updated WHO Recommendation on Tranexamic Acid for the Treatment of Postpartum Haemorrhage 5 Health Information Systems and Monitoring: • Ensure availability of standardized patient charts that support timely, evidence-based clinical case management of women with obstetric complications, including PPH (e.g., recording of time of birth and onset of bleeding, IV dosing of uterotonic, TXA, etc.). • Review PPH content of local health information sources and set locally agreed PPH prevention, treatment, and case fatality reduction targets. • Strengthen collection of a minimum set of PPH data and indicators for use by key actors for programme management, quality improvement, and surveillance (e.g., regional/district manager, hospital maternity quality improvement team.). (See above HMIS considerations for national managers.) • Consider implementing criterion-based audits of clinical records to assess management of PPH (including use of TXA). Inform continuous improvement of evidence-based care for PPH prevention and treatment of women with PPH. 1 World Health Organization (WHO). 2012. WHO Recommendations for the Prevention and Treatment of Postpartum Haemorrhage. Geneva: WHO. 2 WOMAN Trial Collaborators. 2017. 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. 389(10084):2105–2116. doi: 10.1016/S0140-6736(17)30638-4. 3 Shakur H, Beaumont D, Pavord S, Gayet-Ageron A, Ker K, Mousa H. In press. Antifibrinolytic drugs for treating primary postpartum haemorrhage. Cochrane Database Syst Rev. 4 Gayet-Ageron A, Prieto-Merino D, Ker K, Shakur H, Ageron F-X, Roberts I. In press. Impact of treatment delay on the effectiveness and safety of anti-fibrinolytics in acute severe haemorrhage: an individual patient data meta-analysis in 40,138 bleeding patients. Lancet. 5 WHO. 2012. WHO Recommendations for the Prevention and Treatment of Postpartum Haemorrhage. Geneva: WHO. 6 Gayet-Ageron A, Prieto-Merino D, Ker K, Shakur H, Ageron F-X, Roberts I. In press. Impact of treatment delay on the effectiveness and safety of anti-fibrinolytics in acute severe haemorrhage: an individual patient data meta-analysis in 40,138 bleeding patients. Lancet. 7 WHO. 2016. Standards for Improving Quality of Maternal and Newborn Care in Health Facilities. Geneva: WHO. © World Health Organization  Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services Suggested citation. World Health Organization (WHO). Updated WHO Recommendation on Tranexamic Acid for the Treatment of Postpartum Haemorrhage. Geneva, Switzerland: WHO; 2017. Licence: CC BY-NC-SA 3.0 IGO. WHO/RHR/17.21. All reasonable precautions have been taken by WHO, MCSP and USAID to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the WHO be liable for damages arising from its use. The contents do not necessarily reflect the views of WHO, MCSP, USAID, or the United States government. This brief is made possible by the generous support of the American people through the United States Agency for International Development (USAID) under the terms of the Cooperative Agreement AID-OAA-A-14-00028. For further information on the WHO guidelines, please contact email@example.com or firstname.lastname@example.org. WHO Department of Maternal, Newborn, Child and Adolescent Health http://www.who.int/maternal_child_adolescent WHO Department of Reproductive Health and Research http://www.who.int/reproductivehealth http://www.who.int/reproductivehealth
Looking for other reproductive health publications?
The Supplies Information Database (SID) is an online reference library with more than 2000 records on the status of reproductive health supplies. The library includes studies, assessments and other publications dating back to 1986, many of which are no longer available even in their country of origin. Explore the database here.