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Tranexamic Acid May Hurt Head Trauma Survival for One Key Group

— Cheap antifibrinolytic given en route to hospital safe overall in registry

Ƶ MedicalToday
A vial of tranexamic acid over a brain MRI showing bleeding

For suspected severe traumatic brain injury (TBI), giving tranexamic acid to limit internal brain bleeding before trauma center arrival appeared safe -- except in those without evidence of extracranial hemorrhage, a retrospective study suggested.

The 37% 30-day mortality rate among people receiving prehospital tranexamic acid for suspected severe TBI was not significantly higher than the 30% observed among peers who did not receive the antifibrinolytic drug (adjusted OR 1.34, 95% CI 1.16-1.55), according to Patrick Schober, PhD, of Amsterdam University Medical Center, the Netherlands, and colleagues reporting online in .

However, 30-day mortality was elevated when the analysis was limited to people with severe isolated TBI (OR 4.49, 95% CI 1.57-12.87). Further analysis with multiple imputations, to account for missing data, supported the increase in mortality after tranexamic acid administration in this subgroup (OR 2.05, 95% CI 1.22-3.45).

The study was based on the multicenter in the Netherlands. Of its cohort of 1,827 people treated for suspected severe TBI by the Dutch Helicopter Emergency Medical Services, 38% received prehospital tranexamic acid. There were 719 patients with isolated TBI out of 1,375 with confirmed TBI.

People with severe isolated TBI continued to show an excess risk of mortality at 12 months if they had been given tranexamic acid in the prehospital setting (OR 3.31, 95% CI 1.20-9.16).

"The data do not suggest abandoning the current practice of using tranexamic acid in those patients with extracranial injuries and substantial blood loss. Given the available evidence that tranexamic acid can prevent death from exsanguination in trauma patients with severe hemorrhage, it seems prudent to follow the current protocols for such patients," according to Schober's group.

"However, in patients with isolated severe TBI, tranexamic acid administration seems detrimental to survival. This observation suggests that tranexamic acid should be avoided in patients with severe TBI when major extracranial trauma is not suspected," the authors said.

Last year, the CRASH-3 trial showed that tranexamic acid initiated in the hospital reduced mortality in mild-to-moderate TBI but not severe TBI.

Schober's team reported that recipients of tranexamic acid in their study were older and tended to have more severe injury than peers who did not receive the drug.

As a whole, the cohort had a median age of 45 years and 70% of patients were men.

Isolated TBI was defined as a head Abbreviated Injury Score (AIS) of 3 or higher, with neck, spine, thorax, abdomen, extremities, and external AIS of 2 or lower.

There was no evidence of an interaction between tranexamic acid use and anticoagulant use in survival.

Study investigators acknowledged the possibilities of residual confounding and selection bias in their analyses. Their findings may also not be generalizable to other locations or populations, they added.

"The observational data did not allow causal inferences or conclusions to be made about the mechanism by which tranexamic acid might be detrimental to survival, but this drug may induce a shift of the coagulation system toward hypercoagulability, perhaps involving microthrombi with impairment of the cerebral microcirculation and oxygenation," Schober and colleagues suggested.

"Other properties of tranexamic acid, such as modulation of inflammatory responses or promotion of seizure activity, may also play a role. Moreover, transient hypotension after rapid tranexamic acid administration, which can be detrimental to outcomes in patients with TBI, has been described," they noted.

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    Nicole Lou is a reporter for Ƶ, where she covers cardiology news and other developments in medicine.

Disclosures

The study was funded by grants from the Dutch Brain Foundation and the Achmea Healthcare Foundation.

Schober had no other disclosures.

Primary Source

JAMA Neurology

Bossers SM, et al "Association between prehospital tranexamic acid administration and outcomes of severe traumatic brain injury" JAMA Neurol 2020; DOI: 10.1001/jamaneurol.2020.4596.