Red blood cells

The trauma field is aflutter with research and practice changes involving trauma-induced coagulopathy (TIC), the biochemical response to injury, also known as acute traumatic coagulopathy and acute coagulopathy of trauma-shock. Discoveries are still being made in this revitalized area of investigation, and old notions about the coagulation process are being sidelined, along with traditional measures of coagulation. The upshot for laboratorians is, if viscoelastic tests such as thromboelastography (TEG) and thromboelastometry (ROTEM), are not already part of your coagulation testing armamentarium, chances are they soon will be.

"TEG had been used at our hospital, in non-trauma settings, for a long time—a low-level of background use. But in the last two years, there's been intense interest with the trauma surgeons and its uses have increased dramatically," observed Neil Harris, MD, clinical associate professor and co-director of core laboratory at the University of Florida College of Medicine in Gainesville. He estimated that TEG volumes in his lab have quintupled. "That took us by surprise. From the lab's point of view you have to be ready for that, both with staffing and space."

New Look at an Old Test
The new look at TEG—an old test first developed in 1948 and until recently used almost exclusively in open heart and liver transplant procedures—came after a series of revelations about the coagulation process, particularly in trauma. Clinicians already recognized that the classic coagulation cascade model with intrinsic and extrinsic pathways leading to hemostasis—though admittedly complicated—did not fully describe all the factors at work in TIC.

In 1981, University of Colorado researchers described what they called a "bloody vicious cycle" in which acidosis from tissue injury and shock, hypothermia from fluid infusions and exposure, and hemodilution from blood and fluid administrations, kept patients bleeding out and significantly increased their mortality risk.

This model of TIC held sway until 2007, when other investigators proposed activation of the thrombomodulin-protein C system as a key mediating pathway of TIC. Ongoing hypoperfusion, this hypothesis goes, leads to excess activation of protein C, which inhibits thrombin generation, impairs clot formation, and degrades any clots that have formed. This theory—part of a cell-based model of hemostasis occurring on cell surfaces and with three overlapping phases–initiation, amplification, and propagation—"exploded" in the trauma field and "has been what everyone has compared their results to since," said Ernest Moore, MD, professor of surgery and vice chair of research at the University of Colorado in Denver, part of the team that originally proposed the bloody vicious cycle.

PT/INR/PTT: Rudimentary?
Even as investigators continue to piece apart the complicated picture of TIC, the latest evidence reinforces that TIC happens quite early on after trauma, and that it is a highly dynamic process involving both hyper- and hypocoagulative states. Current evidence also devalues traditional measures of coagulation–prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT), not only because they take too long but also because they capture such a small snapshot of the overall coagulation process; as little as 4% of thrombin production, for example.

"Whatever you're going to measure in the lab and give results an hour later it will not represent what's happening to the patient in the current moment," explained Oxana Tcherniantchouk, MD, director of the coagulation consultation service and an assistant professor at Cedars Sinai Medical Center in Los Angeles. "The traditional assays that we use were not designed to evaluate hemostatic process. They were designed to evaluate the level of factors in the plasma."

Moore went so far as to call PT/INR/PTT "rudimentary" in the context of assessing TIC.

TEG and ROTEM: The Basics
TEG and ROTEM are close cousins that assess in real time the entire coagulation process, including fibrin formation and clot rate, strength, stability, and lysis. These two viscoelastic measures of whole blood provide essentially the same information on clot formation, kinetics, and strength, though they operate slightly differently.

With TEG, a heated cup with a blood sample spins at a particular angle and speed, and a torsion wire suspended in the blood detects the clot properties based on impedance. In ROTEM, the heated cup remains stationary and the pin oscillates. Both provide data on six parameters of clot kinetics and properties in values and in a tracing, giving a global assessment of coagulation and cluing trauma surgeons into what type of blood products or other interventions would be most effective in staunching a patient's bleeding.

"These assays save blood products so that we don't unnecessarily transfuse patients," said Tcherniantchouk. "They enable us to understand the exact type of coagulopathy the patient is experiencing. We can transfuse or not transfuse accordingly. This is the personalized medicine we've all been talking about."

Unhealthy Skepticism
Moore said any trauma team worth its salt is already using TEG or ROTEM, but he added that deployment of these tests has been uneven, and not uncommonly met with skepticism, "by the laboratory, blood bank, and anesthesia departments."

Harris attributed this in part to trauma surgeons publishing to their own audience, not in blood bank or clinical pathology literature. "At our institution and others, there's has been a somewhat reflex reaction that this is something the trauma surgeons have developed on their own and we don't necessarily believe that it's true. But more and more people are finding evidence that it is indeed helpful in the right settings," he said.

Tcherniantchouk also suggested that the complicated twists and turns of coagulation are a perfect set-up for resistance to using TEG and ROTEM outside of high-intensity surgeries where the technologies already have a home. She has a coagulation consultation service, so was more than willing to work through implementation issues, which is not the norm. "It was my personal investment of my time, gathering a team, and being on board with surgery and anesthesiology in bringing the assay on board. I believed in that assay, believed in its importance," she recalled. "It was a lot of lot of work and you have to have time to do it."

Logistics Reign Supreme
Labs either considering offering TEG or ROTEM for trauma services or already socked with an uptick in volume, will do well to sit down with the trauma, anesthesiology, and surgery teams and hear them out. "We need to be open to new ideas," said Harris. "Certainly things are proposed to us that don't sound that good or we're not that familiar with, but I think we need to be open and work with the clinical groups to see if it's feasible."

Harris and Tcherniantchouk also advised looking closely at the logistics of location and procedures. Time from blood draw to processing is critical, so the distance between the lab and trauma operating rooms and pre-analytical sample handling are major considerations. "If you stress the specimen, you activate platelets and other blood components. So truly for proper results, samples have to be hand-delivered to the lab," advised Tcherniantchouk. "That's what we do."

When she validated TEG for trauma purposes, Tcherniantchouk compared native versus citrated blood and found no substantive difference. However, to avoid any failed samples that have started to clot by the time they're ready for processing, Cedars Sinai uses citrated samples. "The citrated sample can give you more time to get it to the lab and run it. And you'll have less failure, even for intraoperative settings," she advised. "But each lab has to define what they want to do it and how they will run it and go from there."

The facility layout at the University of Florida requires a completely different approach. With the core lab and trauma facility in different buildings, TEG-related samples make their way to the lab via pneumatic tube. "We actually had to validate that," said Harris. "Especially when looking at platelet function you don't want to shoot blood too rapidly through a pneumatic tube. But it's turned out OK. The trauma team calls and tells us a rapid TEG is coming. The technologist can remove the reagents from the refrigerators, and start to warm them. We can get the test going within five-to-six minutes after the call."
The literature also indicates that TEG is more sensitive to movement and vibrations than is ROTEM. However, Harris recently heard a presentation by a military doctor, who indicated that even in field hospitals in Afghanistan, vibrations had not affected TEG.

Both TEG and ROTEM come with variations off the standard assay, such as reagents to activate tissue factor or inhibit fibrinolysis. Regardless of the assay chosen, both come with learning curves and require absolute attention to detail, according to Moore. "The results are operator-dependent," he observed. "It takes a certain number of studies to be consistent. Once you've reached that threshold everybody pretty much gets the same results, but it takes a while. Labs that relegate a TEG assay to a technician who is not committed to it are going to have disparate information." He added that the manufacturers of TEG and ROTEM both have indicated they have automated, less user-dependent models coming out.

As Moore's team and others continue to crank out research, the TIC testing and treatment landscape will evolve profoundly, with the TEG and ROTEM instruments themselves even miniaturized and used by first responders, Moore predicts. "Clinical practice will change radically within the next five years," he said. "Our understanding of coagulopathy is going to improve rapidly and we'll have a lot of devices available to us that will help us use products in a more sophisticated fashion."