Tag Archives: TXA

Resuscitation

Giving TXA Via An Intraosseous Line?

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Seriously injured patients frequently develop coagulopathy, which makes resuscitation (and survival) more challenging. A few years ago, the CRASH-2 study lent support for using tranexamic acid (TXA) in select trauma patients to improve survival. This drug is cheap and has antifibrinolytic properties that may be beneficial if given for life-threatening bleeding within 3 hours of initial injury. It’s typically given as a rapid IV infusion, followed by a slower followup infusion. The US military has adopted its routine use at forward combat hospitals.

But what if you don’t have IV access? This can and does occur with military type injuries. Surgeons at Madigan Army Medical Center in Washington state tried using a common alternative access device, the intraosseous needle, to see if the results were equivalent. This study used an adult swine model with hemorrhage and aortic crossclamping to simulate military injury and resuscitation. Half of the animals then received IV TXA, the other half had it administered via IO. Only the bolus dose was given. Serum TXA levels were monitored, and serial ROTEM determinations were performed to evaluate coagulopathy.

Here are the factoids:

  • The serum TXA peak and taper curves were similar. The IV peak was higher than IO and approached statistical significance (0.053)
  • ROTEM showed that the animals were significantly hyperfibrinolytic after injury, but rapidly corrected after administration of TXA. Results were the same for both IV and IO groups.

Bottom line: This was a very simple and elegant study. The usual animal study issues come into play (small numbers, pigs are not people). But it would be nearly impossible to have such a study approved in humans. Even though the peak TXA concentration via IO is (nearly significantly) lower, this doesn’t appear to matter. The anti-fibrinolytic effect was very similar according to ROTEM analysis.

From a practical standpoint, I’m not recommending that we start giving TXA via IO in civilian practice. We don’t typically see military style injuries, and are usually able to establish some type of IV access within a reasonably short period of time. But for our military colleagues, this could be a very valuable tool!

Reference: No intravenous access, no problem: Intraosseous administration of tranexamic acid is as effective as intravenous in a porcine hemorrhage model. J Trauma 84(2):379-385, 2018.

Abstracts, Complications

Best Of EAST #9: Is TXA Associated With VTE?

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Most trauma programs can be divided into two types: those that believe in tranexamic acid (TXA) and those that don’t. I won’t get into the details of the CRASH-2 study here. But those centers that don’t believe usually give one of two reasons: they don’t think it works or they think the risk of venous thromboembolism (VTE) is too high.

EAST put together a multi-institutional trial to see if there was an association between TXA administration and subsequent VTE. The results are being reported as one of the paper presentations at the meeting this week. A retrospective study of the experience of 15 trauma centers was organized. A power analysis was preformed in advance, which showed that at least 830 patients were needed to detect a positive result.

Adult patients who received more than 5 units of blood during the first 24 hours were included. There were a lot of exclusionary criteria. They included death within 24 hours, pregnancy, pre-injury use of anticoagulants, interhospital transfer, TXA administration after 3 hours, and asymptomatic patients that had duplex VTE surveillance (huh?). The primary outcome studied was incidence of VTE, and secondary outcomes were MI, stroke, length of stay, and death.

Here are the factoids:

  • There were 1,333 eligible patients identified, and 887 (67%) received TXA
  • Females were significantly (over 2x) more likely to receive TXA (46% vs 19%)
  • 80% of patients given TXA received VTE prophylaxis, whereas only 60% of those who did not receive TXA got prophylaxis (also significant)
  • TXA patients had a statistically significantly higher ISS (27) compared to non-TXA patients (25) but this is not clinically significant
  • Mortality in the TXA group was significantly lower (17% vs 34%)
  • The number of units of blood, plasma, and platelets transfused were significantly lower in the TXA group
  • VTE rate appeared lower in the TXA group, but once multivariate analysis was applied, there was no difference

The group concluded that there was no association between TXA and VTE, but that it was linked to decreased mortality and transfusion need.

My comment: This was a study done the way they are supposed to be! Know your objectives and study outcomes up front. Figure out how many patients are needed to tease out any differences. And use understandable statistics to do so.

But, of course, it’s not perfect. No retrospective study is. Nor is any multi-institutional trial. There are lots of little variations and biases that can creep in. But the larger than required sample size helps with reducing the noise from these issues.

Basically, we have a decent study that shows that the clinical end points that we usually strive for are significantly improved in patients who have TXA administered. We don’t know why, we just know that it’s a pretty good association.

This study shows that the usual reasons given for not using TXA don’t appear to hold true. So hopefully it will convert a few of the TXA non-believers out there. I’m excited to hear more details during the presentation at the meeting.

Reference: Association of TXA with venous thromboembolism in bleeding trauma patients: an EAST multicenter study. EAST Annual Assembly, Paper #13, 2020.

protocols

Massive Transfusion And Tranexamic Acid (TXA)

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Tranexamic acid has been in use for decades, just not for trauma. The CRASH-2 trial was a massive multi-country study showed that there was a slight mortality reduction from 16% to 14.5% in trauma patients who had or were at risk for “significant hemorrhage.” Moreover, there was no difference in vascular occlusive events, blood product transfusions, or need for surgery. Sounds great, right?

The MATTERs trial was initiated by the US military and tried to address some of the perceived shortcomings of CRASH-2 and found an absolute mortality reduction of 6.7%. But it also showed DVT rates that were 12x higher and PE rates 9x higher when this drug was given.

Since those two studies, a significant number of critiques have been published, as well as some additional research. Unfortunately, this has only served to cloud the picture. TXA is very inexpensive and readily available, so there has been a significant move to adopt both in the trauma center, as well as during prehospital care prior to arrival.

The trauma group at Denver Heath published a study of 232 patients with a 20% mortality rate from their injuries. They identified three subsets of patients based on their fibrinolytic response upon presentation to the hospital: physiologic fibrinolysis (49% of patients), hyperfibrinolysis (28%), and fibrinolytic shutdown (23%).

They found that mortality significantly increased in those receiving TXA who were physiologic or hyperfibrinolytic, but unchanged in those in shutdown. They cautioned that giving this drug before the patient’s fibrinolytic status was known could contribute to mortality.

Bottom line: So confusing! And many centers already include TXA in their massive transfusion protocol. Most have not seen unexpected mortality after giving the drug, so the jury is not in yet. Each trauma center should weigh the currently known pros and cons, and decide whether they are “believers” or not. Carefully review all mortalities and thrombotic complications after administration to see if there was any relation to the use of TXA.

References:

  1. Massive transfusion protocols and the use of tranexamic acid. Current Opinion Hematol 25(6):482-485, 2018.
  2. Tranexamic Acid is Associated with Increased Mortality in Patients with Physiologic Fibrinolysis. J Surg Res 220:438-443, 2017.
  3. CRASH-2 Study of Tranexamic Acid to Treat Bleeding in Trauma Patients: A Controversy Fueled by Science and Social Media. J Blood Transfus Article 874920, 2015.
Resuscitation

Giving TXA Via An Intraosseous Line?

Leave a comment

Seriously injured patients frequently develop coagulopathy, which makes resuscitation (and survival) more challenging. A few years ago, the CRASH-2 study lent support for using tranexamic acid (TXA) in select trauma patients to improve survival. This drug is cheap and has antifibrinolytic properties that may be beneficial if given for life-threatening bleeding within 3 hours of initial injury. It’s typically given as a rapid IV infusion, followed by a slower followup infusion. The US military has adopted its routine use at forward combat hospitals.

But what if you don’t have IV access? This can and does occur with military type injuries. Surgeons at Madigan Army Medical Center in Washington state tried using a common alternative access device, the intraosseous needle, to see if the results were equivalent. This study used an adult swine model with hemorrhage and aortic crossclamping to simulate military injury and resuscitation. Half of the animals then received IV TXA, the other half had it administered via IO. Only the bolus dose was given. Serum TXA levels were monitored, and serial ROTEM determinations were performed to evaluate coagulopathy.

Here are the factoids:

  • The serum TXA peak and taper curves were similar. The IV peak was higher than IO and approached statistical significance (0.053)
  • ROTEM showed that the animals were significantly hyperfibrinolytic after injury, but rapidly corrected after administration of TXA. Results were the same for both IV and IO groups.

Bottom line: This was a very simple and elegant study. The usual animal study issues come into play (small numbers, pigs are not people). But it would be nearly impossible to have such a study approved in humans. Even though the peak TXA concentration via IO is (nearly significantly) lower, this doesn’t appear to matter. The anti-fibrinolytic effect was very similar according to ROTEM analysis.

From a practical standpoint, I’m not recommending that we start giving TXA via IO in civilian practice. We don’t typically see military style injuries, and are usually able to establish some type of IV access within a reasonably short period of time. But for our military colleagues, this could be a very valuable tool!

Related posts:

Reference: No intravenous access, no problem: Intraosseous administration of tranexamic acid is as effective as intravenous in a porcine hemorrhage model. J Trauma 84(2):379-385, 2018.

Tips

How To Remember To Give The TXA!

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The CRASH-2 study did a good job of demonstrating the value of giving tranexamic acid (TXA) in patients with major hemorrhage. The kicker is that the data seemed to show that the effect was best if given early, and might even be detrimental after 3 hours.

The reality is that most patients with major hemorrhage will present as a trauma activation. And if they really are bleeding badly, they will probably trigger your massive transfusion protocol (MTP). But at the same time, they will probably keep you very busy, and it’s easy to forget to order the TXA.

How can you make sure to start the TXA promptly on these patients? Easy! Check out this picture:

Yes, that’s a cheat sign right on top of the first cooler for the MTP! Have the blood bank include this sign in the cooler, so that everyone can see it when you crack the cooler open to give the first units of blood products.

In most hospitals, TXA is a pharmacy item. It should be stocked in the ED, and not in a far away pharmacy satellite. And don’t forget that TXA is given twice, 1 gram given over 10 minutes (or just IV push for speed), followed by another gram infused over 8 hours.

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