TXA for Traumatic Brain Injury (JAMA, 2020)

 This multi-center prospective, randomized controlled trial (RCT), which included nearly 1000 participants from the United States and Canada enrolled by paramedics, evaluated the use of tranexamic acid (TXA) administered in the field within two hours of traumatic brain injury (TBI), as well as its impact on long-term neurologic function in moderate or severe TBI patients.

The bottom line: there was no significant improvement in long-term neurologic recovery in those who received TXA compared with the control group.

Patients received either TXA or a placebo prior to hospital arrival. At six months post-injury, both groups had similar rates of favorable neurologic recovery; the difference between the groups was small and not statistically significant. In addition, mortality, disability ratings, and intracranial hemorrhage development were not significantly different between the groups.

In addition to demonstrating that higher doses of TXA may result in an increased rate of seizures, the researchers identified a number of key dosing and safety issues related to the administration of TXA. Overall, while TXA was safe in this study population, the results indicate that administering TXA to patients with suspected moderate or severe TBI without radiographic confirmation will not improve their outcome.

This trial provides additional evidence that administering TXA to TBI patients in the pre-hospital setting, based solely on clinical diagnosis, is not supported by the available data. The potential benefit of TXA may be more pronounced in specific patient subpopulations; therefore, further research should focus on identifying these subpopulations to develop better criteria for patient selection.

To access all of the trial’s methodology, subgroup analysis, dosing information, and how this trial relates to previous studies evaluating the use of TXA, including the CRASH-3 trial, please see the full article published in JAMA.

To read more publications from Dr. Martin Schreiber, visit his official website.

The Hard Question We Still Haven’t Answered: Are We Ready?

I shared a keynote at the North Pacific Surgical Association meeting about an issue I’ve spent my entire career thinking about: readiness. Trauma systems have benefited enormously from lessons learned in military medicine, but the next challenge may not look like the last one. Prolonged care, limited evacuation, and supply shortages are real possibilities, and our civilian hospitals especially in rural areas need plans in place long before a crisis hits.

The progress we’ve made in hemorrhage control, whole blood, TXA, and damage control resuscitation has saved countless lives, both on the battlefield and at home. But the question of whether we’re truly prepared still remains. Readiness isn’t something we can build in the moment. It has to exist before the first patient arrives.

I’m grateful for the thoughtful discussion in Banff and encouraged to see so many leaders committed to strengthening the systems our communities rely on every day.

30th Anniversary of the Oregon Trauma System

 When we celebrated the 30th Anniversary of the Oregon Trauma System, it was more than just a milestone. It was a reflection of how much we've grown and how much farther we have to go to provide high-quality trauma care to all of the communities throughout Oregon.

I have spent my whole career working with trauma and critical care, so I have witnessed firsthand how quickly and effectively an appropriate and skilled intervention can lead to a successful outcome, and ultimately save a person's life. Where a patient's injury occurs directly impacts his or her ability to survive; in many rural communities, the delay in receiving medical attention can be devastating. That is the reason that enhancing trauma responses outside of our urban areas is a top priority for me.

Building a Stronger Rural Network

As part of the 30th Anniversary Celebration, Oregon Health & Science University (OHSU) and Legacy Emanuel Medical Center gave away four separate grants to first responders in rural areas. The purpose of these grants was to allow the first responders to obtain the equipment they need to perform their duties, as well as to receive additional training on their response systems.

While the monetary value of each grant may have been relatively small compared to other awards, the potential impact of the grants was significant. The funds were awarded to paramedics, volunteer rescue groups, and small hospitals that serve some of the most remote and isolated areas within the state of Oregon. These individuals are typically the ones who respond to the scene of an accident when the police arrive, and as such, the support received through these grants had the potential to positively affect the initial treatment of the patient.

Baker City Fire Rescue used its grant to upgrade its existing ambulance to a mass casualty vehicle that includes trauma related supplies and equipment. The Blue Mountain Hospital in John Day used its grant to purchase Stop the Bleed Kits and to conduct training sessions with volunteers and community members. As previously mentioned, both of these improvements are critical in areas that are geographically isolated and far removed from major population centers, as they can limit the access to hospitals during emergency situations.

Collaboration Saves Lives

Working with Legacy Emanuel on this project has been very gratifying. As partners, we have conducted numerous free Stop the Bleed classes throughout Oregon, and have trained hundreds of community members on how to stop bleeding prior to professional assistance arriving at the scene. Additionally, we have collaborated on the Rural Trauma Team Development Course, which is designed to enhance the coordination efforts of smaller hospitals during emergencies.

Trauma care begins long before the patient arrives at the hospital. It begins with the first person to respond to the scene of an accident. By empowering first responders, law enforcement personnel, and volunteers at the local level, we expand the scope of the trauma system and enhance the chances of survival for the patient.

Challenges Remain in Providing Rural Trauma Care

Despite the advances made in providing trauma care, rural trauma remains one of the most challenging problems facing the medical field today. Patients injured in rural areas are approximately two times more likely to die than patients injured in urban areas. While this disparity is reflective of the geographic isolation and limited access to medical facilities, it is not indicative of the skill and dedication of the healthcare professionals involved.

In order to successfully address the issue of rural trauma, healthcare organizations and government entities must collaborate and utilize creative solutions. The use of telemedicine is now allowing medical specialists to provide guidance to rural healthcare providers in real-time. Additional training opportunities are becoming available to enhance the skills of first responders. Additionally, partnerships between organizations such as OHSU and Legacy Emanuel Medical Center will continue to implement cutting-edge trauma care methods in rural communities.

A Sustainable Path Forward

We have learned at OHSU that sustainability is dependent upon the connections that exist between hospitals, agencies, and communities. When knowledge is shared among all parties involved, the overall performance of the system is enhanced. Each component of the system, whether it be the volunteer fireman responding to a call for service or the Level 1 trauma surgeon performing surgery, is essential to the process of saving lives.

A New Horizon

Thirty years ago, the Oregon Trauma System was established as a network of hospitals and emergency services. Its mission was simple yet ambitious – to provide quality trauma care to every Oregon resident. The anniversary celebration of the Oregon Trauma System reminded us that progress is often achieved by taking small steps. A grant, a training course, or a new partnership can have long-lasting consequences. Today, our focus is on continuing to build stronger ties between our rural and urban provider networks.

Every first responder should be given the necessary tools and training to respond with confidence in emergency situations. Every patient should have access to medical care regardless of their geographic location.

Personal Reflection

For me, this milestone represented more than just a celebration. It marked a point in time to reflect on what we have accomplished and what lies ahead. I have worked with countless people who are willing to put themselves in harm's way to assist others. Their dedication and passion inspire me every day.

Each time I travel to rural communities and witness volunteers preparing for emergencies, I am reminded of why this type of work is important. These individuals are the backbone of our trauma system. They remind us that every second counts and that every attempt to improve care has positive results.

My commitment to Oregon's evolving trauma network remains unchanged. We will continue to promote education, innovation, and collaboration. Working together, we will ensure that every patient, regardless of where he or she suffers an injury, receives the best opportunity to survive and recover.

That is the true measurement of a strong and effective trauma system. A system based on expertise, as well as compassion and cooperation that extends to every corner of our state.

Working on the Out of Hospital Tranexamic Acid Trial

I remember the first morning we trained paramedics on this study. We were in a classroom that smelled like coffee and bleach wipes. On the screen was a simple question. Could giving tranexamic acid very early to patients with moderate or severe traumatic brain injury improve recovery at six months. It was a clear question with a hard answer. You only get one chance to do a trial like this the right way.

This project was a team effort across the United States and Canada. Twenty trauma centers. Dozens of emergency medical services agencies. Many helicopters and ambulances. The Resuscitation Outcomes Consortium gave us the backbone. My role was to help design, launch, and run the study at my site and to support the larger network. I worked with surgeons, neurologists, EMS leaders, pharmacists, research coordinators, and ethicists. The logistics alone could fill a book. Study kits had to be stocked on vehicles. Drug accountability had to be perfect. Training had to be repeatable and simple. Randomization had to remain secure in the field where nothing is simple.

The study was double blind and randomized. Patients were enrolled before hospital arrival when there was a strong suspicion of moderate or severe brain injury and the systolic blood pressure was at least ninety. The EMS crew started the study drug within two hours of injury. There were three arms. One gram of tranexamic acid as a bolus in the field followed by a one gram infusion in the hospital. Two grams as a single bolus in the field followed by a hospital placebo infusion. Or placebo bolus in the field followed by placebo infusion in the hospital. In plain words, some patients received a field dose and a hospital dose. Some received a larger field dose only. Some received none.

Working with EMS on an exception from informed consent is humbling. We spent months on community consultation and public disclosure. We spoke with neighborhood groups and community boards. We answered hard questions from families who had lived through brain injury. We carried opt out bracelets on rigs. Every time a patient was enrolled, we notified the family as soon as we could and obtained consent to continue as soon as it was possible. Respect for patients and families shaped every step.

Prehospital trials live or die on workflow. The field clinicians must have tools that fit their world. We built job aids that fit in a cargo pocket. We practiced drawing up the drug while wearing gloves in the back of a moving ambulance. We removed extra steps. We timed each step again and again. We did not want a single paramedic to face a choice between study procedures and direct patient care. Patient care always came first.

Data collection was another lesson in realism. Time of injury is often uncertain. Crews did their best to estimate it from the 911 call and scene facts. We asked for a Glasgow Coma Scale score before intubation when possible. We tracked whether every milliliter of the bolus and infusion went in. We followed patients for six months and called numbers that no longer worked. We learned to expect that some patients would be hard to find. Our data team used careful imputation methods when follow up could not be completed. Even then we treated these data with caution.

The primary outcome was clear. A favorable neurologic outcome at six months on the Glasgow Outcome Scale Extended. The result was neutral. Sixty five percent in the combined tranexamic acid groups versus sixty two percent in placebo. That difference was not statistically significant. Mortality at twenty eight days was also similar between groups. We saw signals that deserved attention. Seizures were more frequent in the group that received a two gram bolus only. Thrombotic events were less frequent in the bolus plus maintenance group than in placebo. These findings did not change the primary result, but they informed the way we think about dosing and safety.

How did that feel as an investigator. In truth, it felt honest. Brain injury has resisted simple answers for decades. A neutral result still advances care when it is credible and complete. We learned that paramedics can safely start study drugs in the field. We learned that a complex network can keep blinding and randomization intact across many miles and many teams. We learned that community engagement can make exception from consent research both respectful and transparent. These are not small lessons. They open the door for future trials that test other time sensitive therapies where the ambulance is the first treatment room.

There were moments that stay with me. A night flight to a rural landing zone where the crew had used a study kit for a young patient. The medic handed me a sealed drug log with steady hands. He was calm and proud. He had done something hard in a hard place and had done it well. Another memory is a family meeting two months later. The patient was improving and the parents wanted to know whether their child had received the drug. We were still blinded. They thanked us anyway for trying to push the field forward. That gratitude held a weight I still feel.

What did I take back to my daily practice. First, the importance of time. Minutes matter in brain injury. Second, the need to match treatment to the biology in front of us. Some patients may benefit from antifibrinolytics. Some may not. Dosing and timing likely matter more than we once thought. Third, the need for better selection. Imaging, biomarkers, and early physiology may help us identify which patients have active bleeding or a risk profile that makes a benefit more likely. Future trials will have to target those patients with more precision.

I also took away renewed respect for the people who make these studies work. Research coordinators who drive to patients’ homes to finish a six month assessment. Pharmacists who count vials at two in the morning. Paramedics who add one more task to a shift full of life and death tasks. Families who trust us during the worst week of their lives. No study happens without them.

Would I do it again. Yes. I would design it with the same care. I would make the tools even simpler. I would add better selection based on early imaging or blood markers if they were available in time. I would keep the same commitment to transparency with our communities. I would keep the same respect for the crews who carry the real weight.

The headline of our paper was that early tranexamic acid in suspected moderate or severe traumatic brain injury did not improve six month neurologic outcome compared with placebo. The story behind that headline is that we built a model for how to test urgent therapies where they matter most. In the field. Early. Safely. With rigor and respect. That is how we will make the next hard answer possible.

To read more about our research, view my publications. 

Early VTE Prevention and the Martin Schreiber Influence

 In 2011, trauma surgeon Dr. Martin Schreiber set out to answer a simple but important question. Should we give every injured patient the same fixed dose of blood-clot prevention, or should we tailor the dose to the person in front of us? His team proposed using a whole-blood test called thrombelastography, or TEG, to read a patient’s real-time clotting profile and adjust enoxaparin accordingly. The goal was straightforward. Prevent more clots in the highest-risk patients without causing more bleeding.

Reading through this work, what stands out is the mindset. Measure what matters. Translate data into decisions at the bedside. Build a pathway busy teams can actually use. That approach, more than any single tool, is what moved the field.

Here is why the study still deserves attention.

It named the problem clearly. After major injury, deep vein thrombosis and pulmonary embolism remain stubborn threats. Fixed dosing is easy to standardize, but not every body responds the same way. Patients with severe trauma, higher body mass, or prolonged immobilization are the likeliest to be underprotected on a one-size-fits-all regimen. Schreiber’s team challenged that habit.

It pushed precision into everyday care. The idea was not to chase numbers for their own sake. It was to use physiology to guide safer dosing. That spirit carried forward. Even though later summaries did not show consistent superiority for TEG-guided enoxaparin in prophylaxis, the field embraced the larger lesson. Today many centers start with higher, weight-aware doses and confirm protection with anti-Xa levels in the patients most likely to be subtherapeutic. Different instrument. Same destination.

It improved how teams communicate. Trauma care is collaborative. Surgeons, intensivists, pharmacists, and nurses need a shared language. Saying “this patient has not reached a prophylactic anti-Xa target” is clearer and more actionable than “this patient seems at risk.” The study helped normalize that kind of practical, measurable target.

It made outcomes the priority. Convenience is not an endpoint. Avoiding clots means fewer scans, fewer interventions, shorter stays, and less long-term harm. Even modest gains matter when multiplied across a trauma service.

So where are we now? In 2025, guidelines and hospital playbooks align around early prophylaxis when bleeding risk is controlled, weight-based starts for many adults, and targeted anti-Xa monitoring in higher-risk cohorts. Typical pathways begin at 40 mg enoxaparin twice daily for most adults outside of brain and spine injury, use 30 mg twice daily with careful reassessment for those populations, and escalate by weight with pharmacist-driven titration. TEG remains valuable in resuscitation and transfusion decisions, where a whole-blood view shines, but routine clot-prevention dosing has largely shifted to tools that are easier to standardize and audit.

Why should people learn about this project now? Because it marks a turning point in how we think about prevention in trauma. It shows how a field can move from a blunt default to a tuned approach without losing speed at the bedside. It also shows how research can succeed even when the original instrument does not become the everyday solution. The win is the principle that survived. Dose the patient, not the protocol.

If you work in trauma, critical care, or any fast-moving service, the takeaway is practical. Measure exposure. Set explicit targets. Adjust in small, safe steps. If you are a patient or caregiver, the message is reassuring. Modern trauma teams do not rely on a single fixed dose and hope for the best. They check, confirm, and individualize.

By that time, Dr Schreiber was serving as chief of trauma, critical care, and acute care surgery at OHSU and as a professor of surgery. His background spans both civilian and military medicine. As a U S Army reservist, he deployed to Iraq and Afghanistan and served as the Joint Theater Trauma System Director, a role centered on turning evidence into daily practice in austere settings. At OHSU, he led a trauma research laboratory with long-standing federal support, focused on hemostasis, resuscitation, and the body’s response to injury. His work has a consistent theme. Measure what matters, translate data into decisions at the bedside, and build protocols that busy teams can use.

For patients with traumatic brain injury, consensus work favors earlier prophylaxis once imaging shows stability, since delays raise clot risk and many patients tolerate carefully timed starts without lesion progression. This approach continues to evolve with updated best practice guidance.

The practical benefits are easy to see. More patients reach protective exposure without increased bleeding risk. Fewer patients suffer preventable clots. Teams speak a common language about timing, targets, and risk. The emphasis on measurement has also strengthened related pathways, including protocols for early prophylaxis in stable traumatic brain injury, and for pharmacist-driven titration in the intensive care unit.

The 2011 study highlights an important pivot point. It asked teams to replace a blunt instrument with a tuned approach. In the years since, trauma programs have kept the same guiding idea while choosing the most reproducible tools. Many centers still use TEG for resuscitation and transfusion choices, where whole blood viscoelastic testing offers insights that routine labs can miss. For clot prevention dosing, services now rely on weight and anti-Xa levels because those tools are easier to standardize, scale across units, and audit for safety and effectiveness.

That is the legacy of Dr. Schreiber’s study. A simple question that changed the conversation, and a mindset that continues to make care safer. You can also explore more of his work and interviews via this podcast.