Impact case study database

Context

Bleeding after trauma is a global healthcare problem responsible for millions of deaths every year (WHO 2018). The CRASH2 trial showed that 9% of hospital trauma deaths could be prevented, estimated as potentially saving more than 100,000 lives per year worldwide [Source 5]. In the UK there are about 7000 in-hospital deaths from injury per year, and therefore 630 lives could be saved every year. A key advantage of TXA is that it is cheap, with a treatment dose costing around £3, meaning that it is applicable to the ‘trauma epidemic’ that is fast growing in the developing world. Economic analysis showed a cost of $64 per life year gained in the UK.

Reach and Significance of Impact

Initial implementation in the UK, was led by the Peninsular CLAHRC [E1] in collaboration with the CRASH2 researchers. The sustaining pathway to impact has been the inclusion of TXA in the NHS England Best Practice Tariff (BPT) for major trauma, a system administered for England and Wales by the Trauma Audit and Research Network (TARN www.tarn.ac.uk) which is Chaired by Coats. The BPT is an additional per patient funding of £2500 payed to NHS Major Trauma Centres if specific quality criteria are met.

Treatment with TXA has been included in BPT criteria from 2012 to 2020. The national use of TXA [R4] in patients who received blood transfusion had changed from near zero in 2010 to 85% in 2016. This was associated with a 19% (95% CI 3%–36%) increase in the national case mix adjusted odds of survival from severe injury between 2008-17 [E2] with a step change in 2012 (coinciding with both a major NHS reorganisation of trauma services and the widespread implementation of TXA treatment). NHS England estimated that these changes created an additional 1600 survivors [E3] by 2018.

In Europe the pathway to impact has been through the European trauma bleeding guidelines, which form the basis of civilian trauma treatment protocols. Originally, in 2007 and 2010, TXA was suggested as a Grade 2C recommendation, meaning that clinicians “should consider giving TXA”. In 2016 the international group responsible for producing the European guidelines evaluated the evidence, including the 2015 Cochrane review [ E3], and upgraded TXA treatment to a (Grade 1A) “give TXA” recommendation. Coats was a guidelines group member and a co-author of this publication [E4]. In the UK this publication was quoted the NICE 2016 guideline NG39 “Major Trauma: assessment and initial management” , which recommend intravenous tranexamic acid as soon as possible in people with major trauma and active or suspected active bleeding.

Continuing research has adjusted the implementation. Our 2018 analysis [E4] showed that relatively few patients received the treatment in the time window (within an hour of injury) when it is most effective. This directly led to a revision of the NHS BPT criteria [E6] for 2019/20 - with the BPT payment now only being made if the patient receives TXA within 1 hour of injury (previously within 3 hours of injury).

The same process has happened in the developing world, for example in South Africa the University of Cape Town, which is a leader in Emergency Care and publishes guidelines, included TXA in their ‘essential medicines’ list in 2018 [E7].

The standard global trauma training course (Advanced Trauma Life Support – ATLS) was updated in 2018 to include a recommendation for TXA use. This is reflected in global civilian trauma management Guidelines. Global military protocols have been rewritten to include TXA in major trauma, for example the US military Joint Trauma System Clinical Practice Guideline (JTS CPG) - Damage Control Resuscitation [E9].

The success of the CRASH2 trial has had an impact wider academic fields, stimulating a number of additional large international clinical trials of TXA [E10]; The WoMAN trial (Death due to post-partum haemorrhage significantly reduced in women given TXA with a risk ratio of 0·81, 95% CI 0·65–1·00; p=0·045); CRASH3 (Death due to head injury reduced in key subgroups); TITCH2 trial (reduction in early death following haemorrhagic stroke); TITCH3 (under application – Coats is a co-applicant); HALT-IT (currently recruiting in gastrointestinal haemorrhage - Coats is a co-applicant and Trial Management Group member).

The Acute Coagulopathy of Trauma was unknown before 2003. There is now an effective treatment, which has become the global standard of care in both civilian and military systems.