Haemostatic drugs for traumatic brain injury

Abstract

Background Traumatic brain injury (TBI) is a leading cause of death and disability. Intracranial bleeding is a common complication of TBI, and intracranial bleeding can develop or worsen after hospital admission. Haemostatic drugs may reduce the occurrence or size of intracranial bleeds and consequently lower the morbidity and mortality associated with TBI. Objectives To assess the effects of haemostatic drugs on mortality, disability and thrombotic complications in patients with traumatic brain injury. Search methods We searched the electronic databases: Cochrane Injuries Group Specialised Register (3 February 2009), CENTRAL (The Cochrane Library 2009, Issue 1), MEDLINE (1950 to Week 3 2009), PubMed (searched 3 February 2009 (last 180 days)), EMBASE (1980 to Week 4 2009), CINAHL (1982 to January 2009), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to January 2009), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to January 2009). Selection criteria We included published and unpublished randomised controlled trials comparing haemostatic drugs (antifibrinolytics: aprotinin, tranexamic acid (TXA), aminocaproic acid or recombined activated factor VIIa (rFVIIa)) with placebo, no treatment, or other treatment in patients with acute traumatic brain injury. Data collection and analysis Two review authors independently examined all electronic records, and extracted the data. We judged that there was clinical heterogeneity between trials so we did not attempt to pool the results of the included trials. The results are reported separately. Main results We included two trials. One was a post-hoc analysis of 30 TBI patients from a randomised controlled trial of rFVIIa in blunt trauma patients. The risk ratio for mortality at 30 days was 0.64 (95% CI 0.25 to 1.63) for rFVIIa compared to placebo. This result should be considered with caution as the subgroup analysis was not pre-specified for the trial. The other trial evaluated the effect of rFVIIa in 97 TBI patients with evidence of intracerebral bleeding in a computed tomography (CT) scan. The corresponding risk ratio for mortality at the last follow up was 1.08 (95% CI 0.44 to 2.68). The quality of the reporting of both trials was poor so it was difficult to assess the risk of bias. Authors’ conclusions There is no reliable evidence from randomised controlled trials to support the effectiveness of haemostatic drugs in reducing mortality or disability in patients with TBI. New randomised controlled trials assessing the effects of haemostatic drugs in TBI patients should be conducted. These trials should be large enough to detect clinically plausible treatment effects.

Strategies for CNS repair following TBI

“…Tranexamic acid was evaluated in a subset of patients in the CRASH-2 trial and showed a trend but no significant difference toward reduced mortality and intracranial hemorrhage growth at 24 to 48 hours . The results from the CRASH-2 trial have been consistent with a subsequent randomized controlled trial evaluating tranexamic acid (Yutthakasemsunt et al, 2013) and an earlier systematic review on the use of hemostatic agents following TBI (Perel et al, 2010). Clinical evaluation of tranexamic acid remains ongoing in the CRASH-3 trial (NCT01402882) which is an international randomized controlled trial (Dewan et al, 2012).…”

Strategies for CNS repair following TBI

“…Tranexamic acid was evaluated in a subset of patients in the CRASH-2 trial and showed a trend but no significant difference toward reduced mortality and intracranial hemorrhage growth at 24 to 48 hours . The results from the CRASH-2 trial have been consistent with a subsequent randomized controlled trial evaluating tranexamic acid (Yutthakasemsunt et al, 2013) and an earlier systematic review on the use of hemostatic agents following TBI (Perel et al, 2010). Clinical evaluation of tranexamic acid remains ongoing in the CRASH-3 trial (NCT01402882) which is an international randomized controlled trial (Dewan et al, 2012).…”

The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition

“…In patients with isolated head injury and traumatic ICH, the use of rFVIIa was shown to have no positive effect on patient outcomes, and even found to be harmful [ 727 , 728 ]. Current evidence does not support the use of any haemostatic drugs, including rFVIIa, for reducing mortality or disability in patients with TBI and related ICH [ 729 ].…”

The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition

“…In patients with isolated head injury and TICH, the use of rFVIIa was shown to have no positive effect on patient outcomes, and even found to be harmful [ 327 , 328 ]. Accordingly, a Cochrane systematic review found no support in favour of rFVIIa treatment for reducing mortality or disability in patients with TBI and related ICH [ 329 ].…”

Strategies for CNS repair following TBI

“…Tranexamic acid was evaluated in a subset of patients in the CRASH-2 trial and showed a trend but no significant difference toward reduced mortality and intracranial hemorrhage growth at 24 to 48 hours . The results from the CRASH-2 trial have been consistent with a subsequent randomized controlled trial evaluating tranexamic acid (Yutthakasemsunt et al, 2013) and an earlier systematic review on the use of hemostatic agents following TBI (Perel et al, 2010). Clinical evaluation of tranexamic acid remains ongoing in the CRASH-3 trial (NCT01402882) which is an international randomized controlled trial (Dewan et al, 2012).…”

The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition

“…In patients with isolated head injury and traumatic ICH, the use of rFVIIa was shown to have no positive effect on patient outcomes, and even found to be harmful [ 727 , 728 ]. Current evidence does not support the use of any haemostatic drugs, including rFVIIa, for reducing mortality or disability in patients with TBI and related ICH [ 729 ].…”

The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition

“…In patients with isolated head injury and TICH, the use of rFVIIa was shown to have no positive effect on patient outcomes, and even found to be harmful [ 327 , 328 ]. Accordingly, a Cochrane systematic review found no support in favour of rFVIIa treatment for reducing mortality or disability in patients with TBI and related ICH [ 329 ].…”

Strategies for CNS repair following TBI

“…Tranexamic acid was evaluated in a subset of patients in the CRASH-2 trial and showed a trend but no significant difference toward reduced mortality and intracranial hemorrhage growth at 24 to 48 hours . The results from the CRASH-2 trial have been consistent with a subsequent randomized controlled trial evaluating tranexamic acid (Yutthakasemsunt et al, 2013) and an earlier systematic review on the use of hemostatic agents following TBI (Perel et al, 2010). Clinical evaluation of tranexamic acid remains ongoing in the CRASH-3 trial (NCT01402882) which is an international randomized controlled trial (Dewan et al, 2012).…”

The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition

“…In patients with isolated head injury and traumatic ICH, the use of rFVIIa was shown to have no positive effect on patient outcomes, and even found to be harmful [ 727 , 728 ]. Current evidence does not support the use of any haemostatic drugs, including rFVIIa, for reducing mortality or disability in patients with TBI and related ICH [ 729 ].…”

The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition

“…In patients with isolated head injury and TICH, the use of rFVIIa was shown to have no positive effect on patient outcomes, and even found to be harmful [ 327 , 328 ]. Accordingly, a Cochrane systematic review found no support in favour of rFVIIa treatment for reducing mortality or disability in patients with TBI and related ICH [ 329 ].…”