THE CASE FOR TXA
civilian protocol based on lessons learned in
military casualties. 32
Similarly, the Royal Flying Doctor Service
of Queensland has been using a functional pre-hospital protocol since 2012, where one gram
of TXA is loaded over 10 minutes followed
by an additional 1 g over about eight hours. 33
In Ohio, a safe and feasible TXA protocol
was established with inclusion criteria based
on the outcomes of CRASH- 2.
Patients with life-threatening hemorrhage
that required blood transfusion or massive transfusion protocol where the time of injury was less
than three hours received 1 g of TXA before
reaching the hospital. A maintenance dose of
an additional 1 g over eight hours was then
ordered by the receiving physician. 11, 34
Several major professional associations recommend the use of TXA. In their updated 2017
guidelines, the Eastern Association for the Surgery of Trauma (EAST) conditionally recommends its routine in-hospital use. 35
In Europe, the multidisciplinary Task Force
for Advanced Bleeding Care in Trauma (ABC-T)
guidelines from 2013 recommend that TXA
be administered as early as possible to trauma
patients who are bleeding or at risk of significant
hemorrhage. Additionally, they recommend
that TXA be administered within three hours
after injury, including the first dose en route to
the hospital. 36, 37
The British National Health System (NHS)
has been using TXA in their trauma protocol since 2012. To date, no significant post-implementation issues have been identified
or published. 38
A recent, large meta-analysis published in
November 2017 evaluated data of over 40,000
patients—the largest meta-analysis comparing
TXA and control to date. 39 The primary goal of
the study was to examine the effect of treatment
delay on the effectiveness of TXA.
The two major randomized clinical trial
data sets included were from the CRASH- 2
trial ( 20,127 trauma patients) 11 and the recent
WOMAN trial ( 20,011 postpartum hemorrhage patients). 6 Logistic regression models
demonstrated that 40% of deaths were due
to bleeding, and 63% of those deaths due to
bleeding occurred within 12 hours of injury. 39
As expected, overall survival was signifi-
cantly increased in the group who received TXA
(odds ratio 1. 2, p = 0.001). Immediate treat-
ment with TXA improved survival by more
than 70% (odds ratio: 1.72, p < 0.0001). The
study determined that for every 15 minutes of
treatment delay, survival benefit decreased by
10% until three hours (at which time there was
no survival benefit). Additionally, there was no
increase in vascular occlusive events with TXA
in this large meta-analysis. 39
Based on all available evidence in major clinical
trials as well as literature of multiple disciplines,
TXA is safe, economical, and effective for pre-hospital use. This is consistent with a recent
review which suggests that TXA can reduce
mortality in bleeding trauma patients without
increasing risk of adverse reaction. 40 Perhaps
more importantly, a recent study demonstrated
that for every 15 minute delay in treatment,
survivability decreases by 10%. 39
The bottom line: use TXA as soon as possible in the setting of massive hemorrhage. Traditionally, it’s given in the setting of hemorrhage
due to trauma, but it has also been readily used
in bleeding associated with postpartum hemorrhage, orthopedic surgery and coronary artery
surgery. It appears to be safe to use in patients
with acute GI bleeding, which will likely be confirmed with the release of the HALT-IT trial
in 2018. TXA is safe and reasonable to use in
pediatrics, and equally in the prehospital setting.
TXA has been endorsed by reputable trauma
associations and is included in recent EAST
and ABC-T guidelines. It’s been used for years
in England as part of the NHS trauma protocol without evidence of unfavorable adverse
effects or outcomes.
TXA should be given to patients with major
hemorrhage as soon as possible. This is supported by a plethora of clinical trials, retrospective reviews and meta-analyses that reveal
its safety and efficacy. Its use in the prehospital setting and upon arrival to most emergency
departments is, therefore, well justified. JEMS
Michael J. Carr, MD, is an EMS fellow in the department of
emergency medicine at Newark Beth Israel Medical Center
in Newark, N.J., and deputy medical director at Monmouth
Ocean Hospital Service Corporation (MONOC) in Wall Township, Neptune, N. J.
Howard K. Mell, MD, MPH, CPE, FACEP, is a physician in the
department of Emergency Medicine, CEP-America/St. Joseph
Medical Center in Joliet, Ill.
Scott D. Weingart, MD, is a clinical associate professor, chief
of Emergency Critical Care, and director of Resuscitation and
Acute Critical Care Unit, Stony Brook Hospital, Stony Brook, N Y.
Joseph E. DiCorpo, BSc, MMSc, PA, is an air ambulance and
international medical consultant based in Atlanta. He’s prac-
ticed anesthesiology, critical care medicine and emergency
medicine. He started as an EMT in 1971 and was an EMS chief
and administrator in Ohio and California.
Mark Merlin, DO, EMT-P, FACEP, is the system medical director
of MONOC EMS. He’s an associate professor at Rutgers School
of Public Health and Medical School. He’s vice-chairman of
emergency medicine and EMS fellowship director at Newark
Beth Israel Medical Center/Barnabas Health. He also serves as
medical director for the New Jersey State Police S WAT Team.
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