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Three Part Question

In [a woman presented with a ruptured ectopic pregnancy] is [tranexamic acid better than placebo] at [reducing mortality]?

Clinical Scenario

The Royal College of Obstetricians and Gynaecologists (1) reports that 11 pregnancies per 1000 are ectopic and that the maternal mortality rate from ectopic pregnancy is 0.2 per 1000. The Healthcare Safety Investigation Branch (2) found of the 12 maternal deaths in early pregnancy in the UK between 2009-14, 9 were related to ectopic pregnancy.

Search Strategy

Medline 1966-09/2019 using PubMed and Cochrane Library 2019 ectopic pregnancy OR ductal pregnancy OR pregnancy of unknown location OR tubal pregnancy AND tranexamic acid. Limit to English language.

Search Outcome

10 Papers identified. 1 conference summary, 5 unsuitable publications (Danish GP practice guidelines, 1966 paper with abstract not available, 3 publications unrelated to ectopic pregnancy), 4 case reports where tranexamic used in management of ectopic pregnancy.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Arowojolu AO, Ogunbode OO 2014,	29 yr old – live cervical pregnancy	Case Report	Live cervical pregnancy treated successfully with IM methotrexate and tranexamic acid followed by suction evacuation with balloon tamponade	TXA used in conjunction with other medical and surgical interventions Patient survived	Case Report
Murphy et al, 2014,	34 yr old – ruptured ectopic pregnancy	Case Report	1g IV tranexamic acid during right-sided salpingectomy	TXA used in conjunction with surgical intervention Patient survived	Case Report
Nurden et al 2018	Unknown age female with ectopic pregnancy	Case Report	Underwent surgery for ectopic pregnancy, tranexamic acid used intra operatively	TXA used in conjunction with other surgical interventions No adverse outcomes reported Patient survived	Case Report Unable to access full text
Grassetto et al. 2014,	37 yr old – ruptured ectopic pregnancy	Case Report	Emergency laparotomy, RBC transfusion and haemostatic therapy. Severe hypofibrinogenaemia was present and treated with 4 g fibrinogen concentrate plus 1 g TXA	TXA used in conjunction with other medical and surgical interventions Patient survived	Case Report

Comment(s)

The available evidence for the use of tranexamic acid in management of ruptured ectopic pregnancy is weak and none of the available papers answer the question proposed above. However, the case reports do not put forward any adverse outcomes when using tranexamic acid in conjunction with other management options.

There is robust evidence for the use of tranexamic acid in other comparable patient populations. The 2013 CRASH 2 trial (3)found Tranexamic acid safely reduced the risk of death in bleeding trauma patients, the 2017 WOMAN trial (4)found tranexamic acid significantly reduced death due to bleeding in patients with PPH and a 2018 review found the use of tranexamic acid significantly reduced blood loss in women undergoing caesarean section.

Clinical Bottom Line

There is no evidence to suggest the use of tranexamic acid increases that rate of adverse outcomes and no patient mortality was reported within the available case studies.

Strong evidence is available to support the use of tranexamic acid in bleeding trauma patients within the emergency department, in post-partum haemorrhage and in those undergoing caesarean section. There is therefore significant overlap in the patient populations where tranexamic acid is effective and it is therefore reasonable to treat haemorrhage due to ruptured ectopic pregnancy in a similar way.

References

1. [No authors listed] Diagnosis and Management of Ectopic Pregnancy (Green-top Guideline No. 21). BJOG. 2016 Dec;123(13):e15-e55. Epub 2016 Nov 3. Erratum in: BJOG. 2017 Dec;124(13):e314.
2. Healthcare Safety Investigation Branch [HSIB]. The Diagnosis of Ectopic Pregnancy. HSIB Bulletin 7 Nov 2018 PUBLICATION REF: 2018/021/1
3. Arowojolu AO, Ogunbode OO. Cervical ectopic pregnancy managed with methotrexate and tranexamic acid: A case report. Afr J Med Med Sci 2014 Dec;43(4):361–4.
4. Murphy NC, Hayes NE, Ainle FBN et al, Jehovah’s Witness patients presenting with ruptured ectopic pregnancies: two case reports. J Med Case Rep. 2014 Sep 19; 8:312.
5. Nurden P, Nurden A, Favier R et al. Management of pregnancy for a patient with the new syndromic macrothrombocytopenia, DIAPH1-related disease. Platelets. 2018 Nov;29(7):737–8.
6. 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 Technol Assess. 2013 Mar;17(10):1–79.
7. 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-controlled trial. Lancet. 2017; 389(10084):2105–16.
8. 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 Transfus 2018 Jul;16(4):329-337.
9. Grassetto A, Fullin G, Cerri G et al. Management of severe bleeding in a ruptured extrauterine pregnancy: a theragnostic approach. Blood Coagul Fibrinolysis. 2014 Mar;25(2):176–9.