Let’s talk about TXA and brain injuries. Maybe we can put to rest the suspicion that TXA creates further injury in patient’s with a TBI. TXA is an amazing tool to use for our trauma patients. There has been so much success TXA that there are trials to see how effective it is for GI bleeds.
most medications new to a service (mine has had standing orders on TXA for
about a year), there are always questions and concerns. One that continually
comes forward is, “does TXA create further harm in a patient with a brain
Curious and in an effort to self educate, I searched and found an article on my favorite blog, EMcrit.
CRASH studies were used to see the effectiveness of TXA and the trauma patient.
The CRASH 3 study was specifically a sub study for the TBI patient. It was ran
as a pragmatic study. Meaning, it was a non-controlled atmosphere and based in
a real life setting with unpredictable variables. Much like a bad trauma
“CRASH-3 was designed to further investigate using
tranexamic acid for patients with traumatic brain injury. This study utilized the following inclusion
Enrollment within hours of injury
Either Glasgow Coma Scale <13 or intracranial
hemorrhage on CT scan
No major extracranial bleeding
This was a massive, pragmatic, double-blind RCT involving
175 hospitals in 29 countries, with a target enrollment of 10,000
patients. Patients were randomized to
receive either saline or tranexamic acid (1 gram loading dose over 10 minutes
followed by a second gram infused over the following 8 hours; this is the same
regimen used in CRASH-2). The primary
endpoint was head injury-related death in the hospital within 28 days of
The utilized saline as the placebo versus TXA. The results showed a reduced mortality rate in patient’s with non-severe TBIs. With an emergency room study such as this, the results were “not statistically significant.” The criteria for a TBI patient is vast. There are too many complications. What proceeded forward was the need to take out the obviously brain dead patients (GCS>9 and fixed pupils). The severe TBI patients would not benefit from TXA just due to the impact of their injury. More severe, the less of a chance of effectiveness.
the mildly injured patient’s proved effective. There was a significant increase
in the decrease of mortality with in 28 days of the patients who received TXA
while suffering from a brain injury. To receive the proper and fair outcome, it
was just a matter realizing that some patients were too sick to save.
“ Subgroup analysis shows benefit from tranexamic acid among patients with a greater hope of recovery. Specifically, tranexamic acid reduced head injury-related death in the subgroup of patients with GCS>8 and also the subgroup of patients with reactive pupils.”
What were the take away and conclusions of the study?
“The conclusion of this article sums things up
nicely: “tranexamic acid is safe in
patients with TBI and treatment within 3 hours of injury reduces head
injury-related death. Patients should be
treated as soon as possible after injury.”
The greatest strength of this study might be an extremely
thorough evaluation for possible adverse events among 12,639 patients. Tranexamic acid was found to be safe, without
increased rates of any adverse events (including thrombosis, seizure, and
The primary endpoint of this study was technically
negative (p-value slightly above 0.05).
This likely reflects the inclusion of moribund patients, who diluted out
the signal of benefit from tranexamic acid.
Numerous subgroup analyses indicate that among patients with a greater
hope of recovery, tranexamic acid is beneficial (figure below). As a statistical rebel, I would consider this
trial to be positive, despite having a technically negative primary endpoint.”
Check out the article at; https://emcrit.org/pulmcrit/crash3/
View the full article