Traumatic Intra-cranial Bleeding

Worldwide, over 10 million people are killed or hospitalised because of
Traumatic Brain Injury (TBI) each year

 

Whether that be through a sports injury, a trip or fall, or a road traffic crash, TBI can have devastating consequences for the people affected

Research Overview

Tranexamic Acid (TXA) for TBI

Bleeding into the brain, or intracranial haemorrhage is common following a head injury. As the volume of blood increases, it exerts pressure inside the skull. If the bleeding continues and the pressure continues to rise, compression of the brain leads to oxygen deprivation, brain herniation, and death. 

TBI patients can experience a loss in physical, behavioural, or emotional functioning after the injury. Even with rehabilitation, only 40-50% of patients recover completely.

The CRASH-3 trial was an international, multicenter, randomised, placebo-controlled trial of the effects of tranexamic acid (TXA) on death and disability in patients with TBI. 

This international trial recruited 12 ,737 TBI patients from 175 hospitals in 29 countries.

Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding was eligible. Once recruited the patients received 1g TXA as a bolus and then an 8-hour infusion of 1g of TXA.

This trial provides evidence that the administration of TXA to patients with TBI within 3h of injury reduces head injury-related death, with no evidence of adverse effects or complications.

A substantial reduction in head injury-related deaths with TXA in patients with mild and moderate head injuries was found but no apparent reduction in those with severe head injury. There was no found increase in disability among survivors.

Current Research

The CRASH-4 Pilot Trial

A fall from standing height in older adults is the commonest cause of major trauma in the UK. 

Traumatic brain injury accounts for half of the trauma admissions in older adults and is a leading cause of death and disability. 

Because the population aged over 70 years is increasing, the number of older adults with TBI will continue to rise.

Most (90%) of the 1.4 million TBI patients seen each year in emergency departments in England and Wales have mild (Glasgow Coma Scale (GCS) score 13-15) head injury, but the term ‘mild’ is misleading in older adults who have higher death rates and worse outcomes than younger patients.

Due to increased use of anticoagulant and antiplatelet drugs, older adults are more likely to suffer intracranial bleeding after mild TBI. TBI is also a strong risk factor for dementia in older adults.

The CRASH-4 trial aims to provide reliable evidence about the effects of early intramuscular TXA on intracranial haemorrhage, disability, death, and dementia in older adults with symptomatic head injury.

For more:

View the CRASH-4 trial Presentation

Read the CRASH-4 trial Summary Protocol

Read the CRASH-4 trial Protocol Study

More Resources

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

CRASH-3 Trial Results

The CRASH-3 trial results show that TXA can help prevent premature death from isolated TBI, a huge global health problem and worldwide killer of thousands. TXA is safe, low cost, and widely available

CRASH-3: The World’s first effective drug for TBI

With an estimated 69 million cases per year, a figure that’s only expected to rise, thanks to CRASH-3 trial we know now that TXA can be used to prevent premature death and disability from TBI

CRASH-3: World Congress on Intensive Care

Prof Ian Roberts talk explains the significance of the results at the World Congress on Intensive Care  

CRASH-3: Trial Results Presented by Professor Ian Roberts

Prof Ian Roberts talks about the trial results, benefits of TXA, and what it means for emergency care in trauma patients worldwide

CRASH-3: Trial Procedure 1

How patients were collected and assessed
Watch here

CRASH-3: Trial Procedure 2

CRASH-3: Estimating Time of Injury

Professor Ian Roberts explains the importance of accurately estimating the time of injury in the CRASH-3 trial

CRASH-3: Randomisation Rhyme – Time is Brain

A poem highlighting the importance of randomising and treating patients as early as possible to prevent further brain damage

CRASH-3: A Doctors Story

A doctor describes a personal experience of TBI and the need to administer TXA treatment as soon as possible after injury

CRASH-3: Time Is Brain

Professor of Trauma Neurosurgery, Antonio Belli emphasises the need to randomise and treat patients as early as possible in order to prevent further damage to the brain

 

CRASH-3: Trial Results

Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial
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CRASH-3: Study Protocol

CRASH-3 – Tranexamic Acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial
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CRASH-3: Intracranial Bleeding Study

Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo-controlled trial (CRASH-2 intracranial bleeding study)
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CRASH-3: Uncertainties

Does tranexamic acid improve outcomes in traumatic brain injury?
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CRASH-3: A Pre-planned Substudy of sample CRASH-3 trial patients

Effect of tranexamic acid on intracranial haemorrhage and infarction in patients with traumatic brain injury: a pre-planned substudy in a sample of CRASH-3 trial patients
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CRASH-3: Neuroprotective Effect of TXA

Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial
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CRASH-3: Accuracy of Time to Treatment

Accuracy of time to treatment estimates in the CRASH-3 clinical trial: impact on the trial results
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CRASH-3: Cost-effectiveness analysis of TXA for the treatment of traumatic brain injury

Cost-effectiveness analysis of tranexamic acid for the treatment of traumatic brain injury, based on the results of the CRASH-3 randomised trial: a decision modelling approach
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CRASH-3: Tranexamic Acid for Traumatic Brain Injury – Authors reply

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CRASH-3: TXA for bleeding trauma patients

Implementation of tranexamic acid for bleeding trauma patients: a longitudinal and cross-sectional study
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CRASH-3: An Intracranial Bleeding Mechanistic Study

A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury
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CRASH-3: Commentary

Outcome measures in clinical trials of treatments for acute severe haemorrhage
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CRASH-3: Intracranial Bleeding Mechanistic Sub-Study

A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial
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CRASH-3: Differential effects of the Glasgow Coma Scale Score and its Components

An analysis of 54,069 patients with traumatic brain injury
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CRASH-3: Exploration of Benefits and Harms

Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms
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CRASH-3: Does tranexamic acid improve outcomes in traumatic brain injury?

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CRASH-3: An Exploratory Analysis of Data from CRASH-2

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-3: TXA in Trauma Patients

Applying results from clinical trials: tranexamic acid in trauma patients
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CRASH-3: Red Blood Cell Transfusion & Mortality

Red blood cell transfusion and mortality in trauma patients: risk-stratified analysis of an observational study
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CRASH-3 Trial: Background Rationale & Overview

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CRASH-3 Trial: Protocol

A randomised, double-blind placebo-controlled trial among 13,000 traumatic brain injury patients

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CRASH-3: Statistical Analysis Plan

Tranexamic acid for significant traumatic brain injury (The CRASH-3 trial): Statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial
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CRASH-3 Trial: Why urgent randomisation and treatment is critical

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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