Since I was the one unprepared at the table, I think it's fitting that I take the counterpoint on this. Skip to the bottom if you just want my final thoughts:
TXA was shown in
CRASH-2 to have a marginal benefit in mortality and show no increased risk of Venous Thromboembolism (VTE in much of the referenced literature). So that's referring to DVT's, PE's, etc. There is a fascinating take on the "marginal benefit" provided by one of the CRASH-2 authors, Dr. Tim Coats, in his interview on EmCrit
here. He postulates that the marginal benefit was due to the usage of TXA on such a large volume of patients that may or may not have met the criteria for rapid transfusion. It was simply left to the physician to decide if they wanted to use it. ---- As a side note, that's hardly a guideline to run a study that may lead to a medicine breakthrough ---- So Dr. Coats suggests that although there is little benefit to a patient three hours later, there may be some. Ultimately, he agrees that administration closest to the time of injury is better. He also suggests survivor bias in that some patients that wouldn't have survived their initial injuries made it a couple days, making TXA appear to have a smaller mortality benefit.
There is a nice peer review of CRASH-2
hereBut let's leave CRASH-2 alone. It has a multitude of imperfections that aren't well understood by those of us that live in the modern world with access to cutting edge trauma care. Those imperfections are also difficult to modify directly to find them applicable in that modern world with cutting edge trauma care. On to something more current.
There has been a lot of criticism of the data obtained for TXA. Click
here for a critical review of CRASH-2. Then click
here for Karim Brohi's scathingly sarcastic response given at SMACC.
So those are pretty opposite views with a heavy film of opinion saturating both.
Let's get some facts in here.
This is the first civilian observational study on TXA in bleeding patients. This was a German registry that contained a whopping 25,000 patients eligible for review. Of that group, 5,765 patients met the criteria of the study (as likely to benefit from TXA). 258 patients received TXA. Those 258 patients were matched with 258 patients from the patients meeting criteria of the study. Each TXA patient and control patient were matched based on age, sex, severity of injury, etc. Their findings?
"Prehospital use of TXA was associated with significantly longer time to death and significantly lower mortality rates at 6, 12 and 24 h."Ok so let's say there's increasing data on TXA improving mortality in the ultra-sick bleeding patients. What about the VTE mentioned before? That has certainly been controversial. Check out the table in
this review. Many are certainly suspicious that the risk of VTE is confounded by numerous factors such as pre-existing co-moribidities, survival bias, and shock state. Check
here for a small study indicating that all of the sick patients they evaluated were at risk of a hypercoagulative state regardless of TXA administration. They were sick patients.
Here's my final take:
The evidence is there that TXA benefits the sickest of the sick bleeding patients. Assign whatever parameter you like as there have yet to be definitive screening tools tested, whether that's the ABC score, shock index, etc. If my patient is a strong candidate for rapid transfusion, TXA makes sense. I don't have whole blood at my disposal, and I would argue that even if you're capable of 1:1:1 (or just RBC and plasma), it's still a diluted product. TXA may still be of benefit. I have not found conclusive evidence that TXA causes VTE. I've only found evidence that sick patients are at risk for VTE. TXA is not the answer to stopping the coagulopathic state. It's just a piece of the puzzle. I'm OK with that.References:
The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients.
Roberts I, Shakur H, Coats T, Hunt B, Balogun E, Barnetson L, Cook L, Kawahara T, Perel P, Prieto-Merino D, Ramos M, Cairns J, Guerriero C.
Health Technol Assess. 2013 Mar;17(10):1-79. doi: 10.3310/hta17100.
www.ncbi.nlm.nih.gov/pubmed/23477634Podcast 67 ā Tranexamic Acid (TXA), Crash 2, & Pragmatism with Tim Coats
February 19, 2012 by Scott Weingart
emcrit.org/podcasts/tranexamic-acid-trauma/Tranexamic acid in trauma: How should we use it?
Lena M. Napolitano, MD, Mitchell J. Cohen, MD, Bryan A. Cotton, MD, MPH, Martin A. Schreiber, MD, and Ernest E. Moore, MD,
Ann Arbor, Michigan
emcrit.org/wp-content/uploads/2012/02/TXA-in-trauma-How-should-we-use-it.pdf
CRASH-2 Study of Tranexamic Acid to Treat Bleeding in Trauma Patients: A Controversy Fueled by Science and Social Media
Sophia Binz, Jonathon McCollester, Scott Thomas, Joseph Miller, Timothy Pohlman, Dan Waxman, Faisal Shariff, Rebecca Tracy, and Mark Walsh
Journal of Blood Transfusion
Volume 2015 (2015), Article ID 874920, 12 pages
www.hindawi.com/journals/jbt/2015/874920/
Tranexamic Acid in Trauma Karim Brohi, TXA denier's handbook
DAS SMACC
vimeo.com/143085660
Wafaisade A, Lefering R, Bouillon B, et al. Prehospital administration of tranexamic acid in trauma patients. Critical Care. 2016;20:143. doi:10.1186/s13054-016-1322-5.
www.ncbi.nlm.nih.gov/pmc/articles/PMC4866028/Tranexamic acid and trauma-induced coagulopathy
Takeshi Nishida, Takahiro Kinoshita and Kazuma YamakawaEmail authorView ORCID ID profile
Journal of Intensive Care20175:5
DOI: 10.1186/s40560-016-0201-0
jintensivecare.biomedcentral.com/articles/10.1186/s40560-016-0201-0Hypercoagulability and other risk factors in trauma intensive care unit patients with venous thromboembolism.
Van Haren RM, Valle EJ, Thorson CM, Jouria JM, Busko AM, Guarch GA, Namias N, Livingstone AS, Proctor KG.
J Trauma Acute Care Surg. 2014 Feb;76(2):443-9. doi: 10.1097/TA.0b013e3182a9d11d
www.ncbi.nlm.nih.gov/pubmed/24398771?dopt=Abstract