Antifibrinolytic drugs for

acute traumatic injury: a

Cochrane review
Clinical

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Clinical questions
Do antifibrinolytic drugs (such as tranexamic acid)
reduce mortality in bleeding trauma patients?
Are there any harmful effects of antifibrinolytics?

Source:

Roberts I, ShakurH, KerK, Coats T, on behalf of theCRASH-2 Trial collaborators. Antifibrinolytic

drugs for acute traumatic injury. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.:
CD004896. DOI: 10.1002/14651858.CD004896.pub3.

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The antifibrinolytic tranexamic

acid (TXA) is a synthetic
derivative of the amino acid
lysine, and has a very high
affinity for the lysine binding
sites of plasminogen.

It blocks these sites and

prevents binding of plasmin to
the fibrin surface, thus exerting
its antifibrinolytic effect.

It has been in clinical use for

more than 40 years.

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Context
World-wide, more than 3 million people die of
injuries each year, many due to excessive
bleeding. Approximately half of the deaths are
due to intentional injury and more than one
million are due to road traffic injuries.
More than 90% of trauma deaths occur in lowincome and middle-income countries.
Antifibrinolytic drugs are widely used in elective
surgery to prevent fibrinolysis and reduce blood
loss. If antifibrinolytics also reduce bleeding in
trauma they could reduce trauma mortality.
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Methods
Searches were carried out of the Cochrane Injuries
Groups specialized register, the Cochrane Central
Register of Controlled Trials, MEDLINE, PubMed,
EMBASE and several other electronic databases.
The relative risk (RR) of death and its 95%
confidence interval (CI) was calculated for each
included trial, and the results were combined in a
fixed effects meta-analysis.
The mean difference (MD) in the volume of blood
transfused was calculated with its 95% CI.

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PICO(S) to assess eligible

studies
Participants: People of any age with acute traumatic injury.

Intervention: Antifibrinolytic drugs: aprotinin, tranexamic

acid (TXA) and epsilon-aminocaproic acid (EACA).
Comparison: Placebo or no antifibrinolytic treatment.
Outcomes: Primary outcomes: death during the follow
up period. Secondary outcomes: adverse events,
specifically vascular occlusive events (myocardial
infarction, stroke, deep vein thrombosis or pulmonary
embolism), surgical intervention, patients receiving blood
transfusion, and volume of blood transfused (units).
Studies: Randomized trials.

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Description of eligible
studies

Four trials met the inclusion criteria.

Two trials, with a combined total of 97 patients,
assessed the effects of aprotinin in trauma patients,
but these trials provided no reliable data for the
review.
Two trials, with a combined total of 20,451 patients,
assessed TXA in trauma patients. The majority (99%)
of patients were in the CRASH-2 trial, which
randomised 20,211 trauma patients with, or at risk of,
significant haemorrhage. It recruited from 274
hospitals in 40 countries. The other trial randomised
240 patients with isolated traumatic brain injury.
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Results
The meta-analysis of the two tranexamic acid trials found that
all-cause mortality was significantly reduced with TXA (RR:
0.90, 95% CI 0.85 to 0.97; p=0.0025). There was no evidence
of statistical heterogeneity (I=0%) between the studies.
There was no evidence of any increased risk of experiencing
one or more vascular occlusive events, either fatal or nonfatal (myocardial infarction, stroke, pulmonary embolism,
deep vein thrombosis) with TXA (RR: 0.84, 95% CI 0.68 to
1.02; p=0.08).
There was no evidence that TXA reduced the risk of surgical
intervention (RR: 1.00, 95% CI 0.97 to 1.03), receipt of blood
transfusion (RR: 0.98, 95% CI 0.96 to 1.01) or the volume of
blood transfused (MD: -0.17, 95% CI -0.39 to 0.05).

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Conclusions: current
findings

The antifibrinolytic agent tranexamic acid reduces

all-cause mortality in bleeding trauma patients,
with no apparent increase in the risk of vascular
occlusive events.
The large numbers of patients studied, from a wide
range of different health care settings around the
world, help the results to be generalised.
Tranexamic acid is inexpensive and easy to
administer. It could easily be added to the normal
management of bleeding trauma patients in
hospitals around the world.
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Conclusions: future research

There is insufficient evidence on the effect of
tranexamic acid in patients with isolated traumatic
brain injury, who do not have significant extracranial bleeding. Further trials are needed to
assess the effects of tranexamic acid on death and
disability in patients with isolated traumatic brain
injury.
There is a need for randomised trials of tranexamic
acid in other conditions where bleeding can be life
threatening or disabling.

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Useful links
Cochrane Journal Club discussion
points
Antifibrinolytic drugs for acute
traumatic injury

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