Traumatic Extra-cranial Bleeding

Each year, worldwide nearly six million people die from trauma – many after reaching the hospital

 

Among trauma patients who survive to reach the hospital, extra-cranial bleeding is a common cause of death, accounting for around 40% of in-hospital deaths

Research Overview

The CRASH-2 trial of TXA for traumatic haemorrhage

The CRASH-2 trial evaluated the effect of TXA on death and vascular occlusive events in patients with traumatic bleeding.

A total of 20,211 adult trauma patients with significant bleeding, who were within 8 hours of their injury, were randomly allocated to receive TXA (1 g over 10 min followed by an infusion of 1 g over 8 h) or matching placebo.

The CRASH-2 trial results showed TXA significantly reduced all-cause mortality in bleeding trauma patients but should be given as early as possible. Treatment within three hours of injury reduces death due to bleeding by about one-third (Relative Risk (RR) = 0.72 (0.63 – 0.83); p<0.001 ).

There was strong evidence that the effect of TXA on death due to bleeding varied according to the time from injury to treatment.

Early treatment (≤1 h from injury) significantly reduced the risk of death due to bleeding (RR 0.68, 95% CI 0.57-0.82; p<0.0001). Treatment given between 1 and 3 hours also reduced the risk of death due to bleeding (RR 0.79, 0.64-0.97; p=0.03).

Treatment given after 3 h seemed to increase the risk of death due to bleeding (RR 1.44, 1.12-1.84; p=0.004). No increase in vascular occlusive events was observed.

On the basis of these results, tranexamic acid was added to the WHO’s Essential Medicines List and to trauma protocols worldwide.

More Resources

Click on watch, read or teach to access videos, publications, and training materials 

 

CRASH-2 Trial Results

An analysis of the 2010 CRASH-2 study shows that TXA should be given as early as possible to bleeding trauma patients; if treatment is not given until three hours or later after injury, it is less effective and could even be harmful.

CRASH-2: TXA Tranman Video

The award-winning TRANMAN video uses unusual visuals to tell the results of the CRASH-2 trial

CRASH-2: TXA Saves Lives

TXA has the potential to save about 100,000 lives a year if patients with significant injuries receive the drug.
A few weeks after the CRASH-2 trial results were released, the British Military incorporated TXA in their protocol to save the lives of injured soldiers.
 
See Surgeon General of the British Armed Forces, Vice Admiral Philip Raffaelli, interviewed about the implementation of the CRASH-2 trial results in the British Military.

CATALYST: Episode on Bleeding Trauma

Episode from Australian TV show, Catalyst focusing on traumatic injuries, what these injuries can do to the blood, and the important role of TXA in treatment of these injuries

TXA in CASUALTY

A scene from the TV show Casualty where a patient with a femoral arterial stab wound is treated with TXA

Karim Brohi discusses Tranexamic Acid in Trauma

CRASH-2 Trial – Comments from Collaborators – Spanish Version

CRASH-2 Trial Results

Effects Of Tranexamic Acid On Death, Vascular Occlusive Events, And Blood Transfusion In Trauma Patients With Significant Haemorrhage (Crash-2): A Randomised, Placebo-controlled Trial
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CRASH-2 Trial: TXA Manga Style

Clinicians are bombarded with thousands of pieces of new information every day.  CRASH-2 used a unique Manga-style approach to help communicate the results of the CRASH-2 trial.  See the drama ensue when doctors and nurses work to save patients bleeding from traumatic injuries
Read the story

CRASH-2 Trial: Time

The Importance Of Early Treatment With Tranexamic Acid In Bleeding Trauma Patients: An Exploratory Analysis Of The Crash-2 Randomised Controlled Trial
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CRASH-2 Trial: Baseline Risk

Effect of tranexamic acid on mortality in patients with traumatic bleeding: prespecified analysis of data from randomised controlled trial
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CRASH-2 Trial: Intracranial Bleeding

Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study)
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CRASH-2 Trial: Economics

Cost-Effectiveness Analysis of Administering Tranexamic Acid to Bleeding Trauma Patients Using Evidence from the CRASH-2 Trial
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CRASH-2 Trial: Deaths Averted

Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial
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CRASH-2 Trial: Interaction Not Confounded

Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms
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CRASH-2 Trial: Exploring Mechanisms

Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial
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CRASH-2 Trial: Generalisability

Applying results from clinical trials: tranexamic acid in trauma patients
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CRASH-2 Trial: Trauma Promise

A promise to save 100 000 trauma patients
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CRASH-2 Trial: Policy Promise

Tranexamic acid in trauma: we need stronger global health policy
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CRASH-2 Trial: Heart Technology Assessment Report

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
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CRASH-2 Trial: Effect of Treatment Delay on the Effectiveness and Safety of Antifibrinolytics in Acute Severe Haemorrhage

A Meta-analysis Of Individual Patient-level Data From 40138 Bleeding Patients
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CRASH-2 Trial Meta-Analysis: Effect of Delayed TXA treatment

Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40138 bleeding patients
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CRASH-2 Trial: Antifibrinolytic Therapy 

New data and new concepts
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CRASH-2 Trial: Consent Rituals on Mortality

Effect of consent rituals on mortality in emergency care research
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The CRASH-1 Trial Collaborators

Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months
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The CRASH-1 Trial Collaborators

Effect of intravenous corticosteroids on death within 14 days in 10,008 adults with clinically significant head injury (MRC CRASH Trial): a randomised placebo-controlled trial
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Analysis of the CRASH-2 and WOMAN trials

Risk factors for blood transfusion in traumatic and postpartum hemorrhage patients
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CRASH-2 Trial: Implementation of tranexamic acid for bleeding trauma patients

A longitudinal and cross-sectional study
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CRASH-2 Trial: Is tranexamic acid effective in traumatic brain injury?

Evidence for an effective therapy
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CRASH-2 Trial: TXA In Trauma Patients

Applying results from clinical trials
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CRASH-2 Trial: Prognostic Model

Predicting early death in patients with traumatic bleeding: development and validation of the prognostic model
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CRASH-2 Trial: Correspondence

The CRASH-2 trial was not about global scientific supremacy
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CRASH-2 Trial: An Analysis of CRASH-2 Cohort

Risk Factors for Vascular Occlusive Events and Death Due to Bleeding in Trauma Patients
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CRASH-2 Trial: Antifibrinolytic drugs for acute traumatic injury

Cochrane Database of Systematic Reviews
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CRASH-2 Trial: An Example in TBI

Covariate adjustment increased power in randomized controlled trials
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CRASH-2 Trial: Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage intracranial bleeding study

The effect of tranexamic acid in traumatic brain injury–a nested randomised, placebo-controlled trial
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CRASH-2 Trial: Rationale & Overview

Tranexamic acid for the treatment of significant traumatic brain injury: an international randomised, double-blind placebo-controlled trial
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CRASH-2 Trial: Protocol Summary

A large randomised placebo controlled trial among trauma patients with or at risk of significant haemorrhage, of the effects of antifibrinolytic treatment on death and transfusion requirement
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CRASH-2 Trial: Statistical Analysis Plan
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CRASH-2 Trial: Presentation

Tranexamic acid safely reduces mortality in bleeding trauma patients. Here we present the evidence
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More Treatments

TXAcentral is a resource for health professionals caring for people with acute bleeding
TXAcentral brings together randomised trial evidence on the effectiveness and safety of tranexamic acid
Data on many of the trials are also available at the freeBIRD website

In trauma patients with significant bleeding and those with traumatic brain injury (TBI), TXA has been  shown to reduce mortality in both extracranial and intracranial bleeding

Postpartum Haemorrhage (PPH) is the leading cause of maternal death worldwide, responsible for around 100 000 deaths each year. TXA given as quickly as possible after birth and no later than 3 hours, reduces death due to bleeding and the need for surgery to stop bleeding

GI Bleeding is a common emergency that causes substantial mortality and morbidity worldwide. TXA was found to not reduce deaths from GI bleeding and showed an increased risk of thromboembolic events

Every year there are over 300 million surgical procedures worldwide. Bleeding is an important complication and many patients require a blood transfusion. TXA reduces blood loss in surgical patients by about one‐third. However, the effects of TXA on thromboembolic events and mortality in surgery are uncertain

There is ongoing research looking at how Tranexamic Acid (TXA) could be utilised for other bleeding conditions