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Three Part Question

In [women presenting to the emergency department with post-partum hemorrhage] does the [administration of tranexamic acid compared with placebo] [reduce mortality]?

Clinical Scenario

A 26-year-old multiparous female presents to a rural emergency department. She had a precipitous delivery on her way into the hospital. On arrival in emergency department, she is having a significant amount of vaginal bleeding and is beginning to become symptomatic, though her blood pressure is currently stable. You contact Obstetrics, obtain labs and blood type and cross, and begin uterotonics. You wonder if adding tranexamic acid will improve this patient’s outcome.

Search Strategy

Medline 1966-05/18 using PubMed, CINAHL, Cochrane Library (2018), and Embase
[(exp tranexamic acid) AND [(exp post partum haemorrhage) OR (exp post partum hemorrhage)]. Limit to English language.

Search Outcome

26 studies were identified; only two trials were identified in which tranexamic acid was compared with standard care (or placebo) for treatment of post-partum haemorrhage.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Woman Trial Collaborators April 2017 UK	20060 female patients with the clinical diagnosis of post partum hemorrhage randomized to IV tranexamic acid vs placebo.	Multicenter RCT	Composite outcome of death from all causes and hysterectomy within 42 days of giving birth	No significant difference (5.3% vs 5.6%) in composite outcome of mortality or hysterectomy, but significant reduction (1.5% vs 1.9%) in deaths due to bleeding.	The primary endpoint was altered after initiation of the trial; diagnosis of PPH made clinically and no assessment of inter-rater reliability in making this determination
Ducloy-Bouthors et al. April 2011 France	144 female patients with greater than 800mL post partum hemorrhage at 2 hours post delivery randomized to IV tranexamic acid vs standard of care	Multicenter RCT	Reduction in blood loss during post partum hemorrhage	Significant reduction (170 mL vs 221mL) in blood loss	Unblinded; not patient centered outcome; small study not powered for side effects or mortality; performed in tertiary centers in high income country so possible limited generalizability

Comment(s)

Postpartum hemorrhage is a significant cause of morbidity and mortality among young females worldwide. Tranexamic acid is an antifibrinolytic agent discovered in the 1950’s while searching for a treatment for postpartum hemorrhage. Recent studies demonstrate significantly improved patient outcomes when tranexamic acid is administered. The smaller unblinded study found a reduction in blood loss as well as improved time to bleeding cessation. The WOMAN trial found that there was a reduction in deaths from bleeding, as well as a reduction in the need for laparotomies to control bleeding. There does not appear to be any significant side effects associated with the administration of tranexamic acid, specifically no increased incidents of thrombosis. It also appears to have a time related effect. The most benefit was seen when it was administered within 3 hours of onset of post partum hemorrhage. This is consistent with what has been seen in studies for other indications, including trauma.

Editor Comment

CF

Clinical Bottom Line

In women presenting to an Emergency Department with post-partum hemorrhage, tranexamic acid administration decreases mortality from bleeding, particularly when administered early.

References

1. Woman Trial Collaborators 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-cont Lancet 2017;389(10084):2105-2116.
2. Ducloy-Bouthors AS, Jude B, Duhamel A, Broisin F, Huissoud C, Keita-Meyer H, Mandelbrot L, Tillouche N, Fontaine S, Le Goueff F, Depret-Mosser S, Vallet B; EXADELI Study Group, Susen S. High-dose tranexamic acid reduces blood loss in postpartum haemorrhage Crit Care 2011;15(2):R117