Tranexamic Acid Saves Lives

Tranexamic acid saves lives, reduces transfusions. So why does no one use it? (Review, BMJ)
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Jan
05
2013


Tranexamic Acid: Underused for Uncontrolled Bleeding?
Tranexamic acid is a simple little molecule, just a synthetic derivative of the amino acid lysine. But it’s also a potent pro-hemostatic drug that binds plasminogen and plasmin and stops the degradation of fibrin (the stuff in blood clots).

In the U.S., tranexamic acid is sold as Lysteda (oral) and Cyklokapron (I.V.) The drug has long been known to reduce the need for blood transfusion in surgery patients. However, almost no one uses tranexamic acid in the U.S., where it had only $17 million in sales for 2011, mostly for the reduction of bleeding during dental procedures.

It’s not for a lack of evidence: The U.K.-based CRASH-2 trial showed tranexamic acid given early after trauma saves lives. In this meta-analysis in BMJ, Katharine Ker, Phil Edwards, Pablo Perel, Haleema Shakur, and Ian Roberts argue it’s time to stop doing placebo-controlled randomized trials to see if tranexamic acid reduces transfusion requirements, because it’s clear it does. The point now should be to demonstrate its safety and whether tranexamic acid improves clinical outcomes as a treatment for trauma and other bleeding causes.

They analyzed 129 trials enrolling 10,488 patients between 1972 and 2011. As you could guess, the older studies were methodologically poor by today’s standards, and often unblinded. Nevertheless, tranexamic acid reduced the need for blood transfusion by one third (risk ratio 0.62, 95% confidence interval 0.58 to 0.65; P<0.001). After restricting the analysis to blinded trials, tranexamic’s 33% transfusion-sparing effect was virtually unchanged.

The trials were inconclusive as to whether tranexamic acid also caused blood clots, or prevented them, but the safety trends were favorable. For example:

The risk ratio for myocardial infarction with use of tranexamic acid was 0.68 (0.43 to 1.09; P=0.11);
For deep vein thrombosis 0.86 (0.53 to 1.39; P=0.54);
and pulmonary embolism was 0.61 (0.25 to 1.47; P=0.27),
but for stroke it was 1.14 (0.65 to 2.00; P=0.65).
Tranexamic acid’s effect on mortality was likewise unclear, but encouraging — a 0.67 risk ratio (0.33 to 1.34, p=0.25). Cumulative meta-analysis showed that reliable evidence that tranexamic acid reduces the need for transfusion has been available for over 10 years.

Why Don’t Doctors Use Tranexamic Acid?
So tranexamic acid stops bleeding, reduces transfusion requirements, and saves lives in bleeding trauma patients. And unlike NovoSeven, it doesn’t cost $1,200,000 a gram (or about $10,000 per 8 mg dose, given every 2 hours). So why is almost no one in the U.S. prescribing tranexamic acid — for G.I. bleeding patients, intracranial hemorrhages, trauma, and surgical misadventures?

Ian Roberts, principal investigator of the CRASH-2 trial demonstrating tranexamic acid’s benefit in trauma, chalks it up to the recency of CRASH-2 and unawareness among physicians of the drug’s benefit. While conducting other trials testing tranexamic acid in postpartum hemorrhage (which kills 100,000 women each year globally) and G.I. bleeding, they’re promoting the CRASH-2 findings in film, a creepy, yet catchy jingle and a manga cartoon, all of which are clickable from the CRASH-2 website.

The U.S. military already gives tranexamic acid to soldiers with severe bleeding (their tranexamic acid dose: 1 gram in 100 mL crystalloid, administered over 10 minutes within 3 hours of injury, followed by another gram after fluid resuscitation has begun), and included tranexamic acid in its revised protocol for combat casualties. Tranexamic acid is almost absurdly cheap at $100 per gram in the U.S., and less in other countries.

Enough data is in that tranexamic acid’s should become a standard treatment for trauma and possibly other causes of severe hemorrhage, Tim Coats (CRASH-2 co-author) tells Scott Weingart in this EMCrit podcast:



Katharine Ker, Phil Edwards, Pablo Perel, Haleema Shakur, and Ian Roberts. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ 2012; 344:e3054.

BLADEMDA said:

The U.S. military already gives tranexamic acid to soldiers with severe bleeding (their tranexamic acid dose: 1 gram in 100 mL crystalloid, administered over 10 minutes within 3 hours of injury, followed by another gram after fluid resuscitation has begun), and included tranexamic acid in its revised protocol for combat casualties.

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Yes we do -

Here's the clinical practice guideline (2.1 MB pdf) we follow for those who are curious. It talks about TXA on page 4 and in appendix C (page 14).

They get a gram of TXA in the trauma bay and we start an infusion at 125 mg/hr to be run for 8 hours. Usually it's pretty clear who's going to need it.


Couple interesting bits

page 3 said:

Platelets: Apheresis platelets collected in theater are not-FDA compliant due to the lack of complete infectious disease testing of donors prior to collection. Efforts have been made to push platelets as a component of therapy to Level III and some Level II facilities throughout the theater. These are available as platelet pheresis packs that are obtained from donors within theater.

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I'm at a role 3 facility (3's are the largest in-theater hospitals, with essentially US level 1 capability - multiple subspecialist surgeons on staff) and we do collect platelets here. Mostly from hospital staff but some of the nearby fobbit units have regular donors.

AFAIK the role 2 facilities (more like the classic forward resuscitation surgical suites, typiclaly one or two ORs, a couple surgeons, anesthesiologists and/or CRNAs, small blood bank) don't collect platelets. Most do have a walking blood bank set up and can use whole blood.

page 6 said:

The operating room must be kept as warm as possible; ideally 108°F or greater.

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We keep the ORs over 100 ... and this is the only place I've ever been where the surgeons don't gripe about it being too hot. 🙂

We use it a lot for ortho- especially for joints. There's a hospital protocol. We've had combined orthopedic surgery and anesthesia conferences to discuss its use...

At my program we use it all the time for traumas. I have never used it outside a trauma case. As far as I can tell it is a pretty benign drug and probably should be used more liberally. Also, I understand that it is pretty cheap.

We use it for spine fusions, depending on ortho attendings preference.

Our ortho is trying to get it on formulary for TKA to reduce hematoma formation after surgery to reduce infections.

Our heart surgeons want amicar. So do out spine guys for certain cases

We've been using it for our hearts as of late... We used to use Amicar but haven't had that in well over a month. The heart dosing is pretty different than the trauma protocol dosing, I honestly don't know how much data supports the new protocols we're running. I'd be interested to hear if other people are using it for pump cases and what doses they're using (and/or what papers they're using to guide their dosing).

Yes it does.

http://crash2.lshtm.ac.uk/

I use this site

I used it routinely for pump cases during my first CV month earlier this year. Two different ways that I was taught:

1: 1 g bolus after induction and PA placed during surgical draping with 1 g diluted into a 500 CC bag of LR that goes at 125 cc per hour into the VIP port of the PA. This is also the line that our pressors etc would go so it's essentially running in our carrier fluid.

2: 2 g into 500 cc bag used as above.

I don't really have any experience doing pump cases without it so I can't compare.

Our trauma surgeons prefer Amicar and use high dollar factors not infrequently.

Where I'm at the blood bank attaches it to the second set of coolers during massive transfusion protocol. 1GM over 10 min, 1G over 8 hr infusion.

For hearts now w/o Amicar, 1GM load after induction, 2mg/kg/hr infusion and 1GM in pump.