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07-07-2011 | Article

CRASH-2 hints at tranexamic acid benefits in intracranial hemorrhage


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MedWire News: Tranexamic acid is associated with a trend toward less hemorrhage growth and fewer new ischemic lesions when given to patients with traumatic intracranial hemorrhage, shows a study nested within the CRASH-2 trial.

As reported in the BMJ, the effects of tranexamic acid were not statistically significant, and the confidence intervals were wide, leading the CRASH-2 investigators to conclude that "neither moderate benefits nor moderate harmful effects of tranexamic acid in patients with traumatic brain injury can be excluded."

But editorialist Yvo Roos (Academic Medical Center, Amsterdam, the Netherlands) argued that the analysis "justifies a re-evaluation of the possible benefit of low-dose short-term [tranexamic acid] in patients with other types of intracranial hemorrhage."

The current study - the CRASH-2 Intracranial Bleeding Study - included 270 adult trauma patients within 8 hours of injury who had or were at risk for significant extracranial bleeding, and also had traumatic brain injury.

In all, 133 patients were randomly assigned to receive tranexamic acid, at a loading dose of 1 g over 10 minutes, followed by an infusion of 1 g over 8 hours. These patients had an average hemorrhage growth of 5.9 ml between computed tomography scans at baseline and 24-48 hours.

By comparison, the 137 patients given placebo treatment had an average 8.1 ml hemorrhage growth.

After adjusting for Glasgow Coma Score, age, time to scans, and initial hemorrhage volume, this amounted to a 3.8-ml reduction in growth in the tranexamic acid group - but this was nonsignificant, with a 95% confidence interval of -11.5 to 3.9 ml.

Likewise, new focal cerebral ischemic lesions appeared in 5% of patients in the tranexamic acid group versus 9% of those in the placebo group, equating to an adjusted 49% risk reduction, but with a 95% confidence interval that encompassed from a 82% reduction to a 44% increase in risk.

There was also a nonsignificant 53% reduction in mortality risk, with 11% of the tranexamic acid group and 18% of the placebo group dying within 28 days of randomization.

In his editorial, Roos noted that tranexamic acid has been avoided by neurologists because its effectiveness against bleeding is offset by an increase in cerebral ischemia. He suggested that the relatively low dose and short duration of treatment in CRASH-2 may explain its improved safety profile, and that this "might be the right regimen to use in other patients with intracranial hemorrhage."

Roos pointed out that there is often a delay before patients with aneurysmal subarachnoid hemorrhage can undergo aneurysm occlusion, and that about a third of patients with intracerebral hemorrhage have early hematoma growth.

"As well as the CRASH-2 trial we therefore need new trials investigating short course low dose [tranexamic acid] in patients with aneurysmal subarachnoid hemorrhage and intracerebral hemorrhage," he concluded.

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Eleanor McDermid