Tranexamic acid for traumatic brain

injury: a systematic review

and meta-analysis

Shahriar Zehtabchi, MD a,
Samah G. Abdel Baki,MDa,
Louise Falzon, BA, Daniel K.
Nishijima, MD

Introduction
an estimated 1.4 million emergency department (ED)
visits
Trauma
275000 hospitalizations
Brain Injury
52000 deaths each year
progressive intracranial bleeding, cerebral edema,
increased intracranial pressure, subsequent cerebral
Secondary
ischemia
Brain Injury
worsened by posttraumatic coagulopathy
Antifibrinolyt
ic agent
tranexamic
acid (TXA)

Outcome

Does administration of TXA (intervention) compared to

placebo (comparison) improve patients' outcomes such
as reduction inmortality, neurologic function, and
hemorrhage progression (outcome)?

Methods

Study Design :
Randomized controlled trials (RCTs) or quasi-RCTs

Literature Search :
Predesigned search strategy developed by an expert medical
librarian (LF)
MEDLINE (1946 to March 2014),
EMBASE (1980 to March 2014),
CINAHL (1981 to March 2014) and
the Cochrane Library were searched.
In addition we were look for relevant presented abstracts and
contacted the experts to solicit information about possible
ongoing, unpublished studies.

Methods
Data extraction
Data from the identified studies were abstracted independently by 2 of the
authors (SZ and SGA) using a standardized form.

Quality assessment
Grading quality of evidence and strength of recommendations criteria to assess the
quality of the included trial and rate the level of evidence

Quantitative data synthesis

The effect of TXA on dichotomous outcomes was assessed using a random effects
model because the trials were expected to be heterogeneous in their design and
patient populations. Relative risk and 95% CIs were calculated. We quantitatively
synthesized 3 outcome measures from the 2 randomized trialsinhospital

mortality, unfavorable functional status, and significant

hemorrhage growth. Statistical heterogeneity was examined using the 2
and I2 tests for heterogeneity. Data were analyzed using STATA 11.0.

Methods

Methods

Result

Discussion
Improving the outcome of brain injury patients largely
depends on minimizing the secondary brain insults

Secondary insults include hematoma

expansion, cerebral edema, increased
intracerebral pressure, infection, hypoxia, and
.
Thecoagulopathy
brain tissue contains
large amounts of thromboplastin.
This substance is released in high concentration into the
blood stream after physical trauma to the parenchyma,
causing disturbance in coagulation processes.

In addition, damaged cerebral endothelium

activates platelets as well as clotting cascades
to produce intravascular thrombosis and
depletion of coagulation factors

Tranexamic acid
a lysine
analog activation. This
Functions by inhibiting
plasminogen

action allows mature fibrin clots to be maintained and

coagulation to continue uninhibited.

Mechanism
1. TXA, as an antifibrinolytic agent,
may limit fibrinolysis and thus ICH
progression. Fibrinolysis is common
in TBI and has been shown to be a
strong independent predictor of ICH
progression.

2.TXA may inhibit the effect of

tissue plasminogen activator,
which plays a role in perilesional
edema

Limitations
There was some heterogeneity between
identified studies, particularly in the
inclusion criteria
The included studies did not account
for patients receiving anticoagulants
or antiplatelet agents.
The mechanism of injury could be a
confounder that needs to be examined
in future trials.
The meta-analysiswas performedwith
only 2 trials.

Conclusion
Pooled results from the 2 RCTs demonstrated
statistically significant reduction in ICH progression with
TXA and a non statistically significant improvement of
clinical outcomes in ED patients with TBI.
Despite an excellent safety profile, further evidence is
required to support the routine use of TXA in patients
with TBI.
An ongoing, international, multicenter, phase III trial
(CRASH-3) [15] evaluating the use of TXA on death and
disability in patients with TBI with a planned enrollment
of 10000 patients will certainly shed light on this
particular question.