January 2024—Viscoelastic assays and other coagulation tests were front and center when CAP TODAY publisher Bob McGonnagle on Nov. 20 convened seven people in an online roundtable. Oksana Volod, MD, and Eric Salazar, MD, PhD, and five company representatives weighed in on, among other things, appropriate test use, automation, and laboratory-developed tests. What they said begins here; CAP TODAY’s guide to coagulation analyzers begins here.
Oksana Volod, you have now written the first book on viscoelastic testing that’s designed to speak directly to pathologists and others in clinical laboratories [https://bit.ly/CT-1023-visco]. Where are we with the adoption of viscoelastic testing? Will it become more mainstream now in the repertoire of the people who do thrombosis and hemostasis testing?
Oksana Volod, MD, director of coagulation consultative service and professor of pathology, Cedars-Sinai Medical Center; associate professor of pathology, David Geffen School of Medicine at UCLA: TEG [thromboelastography], the first viscoelastic assay, was developed before partial thromboplastin time and was initially used in liver transplant and cardiac surgeries. In 2000, when we had a cell-based model of hemostasis, there was an understanding that there was a role for platelets, red blood cells, and other cells or elements to form a clot, and that plasma-based assays, like PTT and PT, will not provide comprehensive information. That’s when interest in viscoelastic testing emerged and when it was adopted, mainly by anesthesiologists, perfusionists, people who were in the OR. Laboratories were not that receptive because there were validation steps they would have to be involved in, and there was a disconnect at some point between laboratorians and anesthesiologists and surgeons. They wanted to bring viscoelastic assays in-house, but laboratories were resistant and questioned where the device would be located—in the laboratory or at the point of care. However, the laboratory was instrumental in validation and in maintaining the competency of their personnel. The whole process was a collaboration.
That link was truly established when clinicians started to use viscoelastic testing—Quantra, TEG, ROTEM Sigma—for patients with COVID in the ICU and on ECMO and for anticoagulation management. All were off-label use. Then the FDA issued guidance regarding the expansion of whole blood viscoelastic measurements to COVID-19 patients. These forces will potentially move forward the use of this testing in the hospital setting.
Some are still not receptive; they would like more randomized controlled studies to be done. The groups who use viscoelastic testing are still mainly in ICU and cardiac and liver surgeries; OB-GYN wants to use it but it’s not yet FDA approved in that setting.
Jeff Light, HemoSonics is a point-of-care coagulation company. What are your thoughts on this and how far has viscoelastic testing come?
Jeff Light, global product manager, HemoSonics: Historically over the past 10 to 20 years we have seen hesitancies to get started and significant limitations in functional viscoelastic testing implementation. At some point, clinicians in the ORs started realizing that a potential solution existed. Time is critical when treating an acutely bleeding patient, so clinicians took it into their own hands to attempt to bring viscoelastic testing into the ORs and clinical settings. While this was fueled by the right intention, it did not foster an adequate team-based approach to perioperative bleeding management. That led to a disconnect between the clinical areas and the laboratory and has historically caused or exacerbated frustrations such that neither the laboratory, clinical areas, nor patients receive the full, united benefit of this diagnostic tool. As more people are recognizing the clinical benefit of viscoelastic testing, they are exploring solutions to the historical implementation and sustainability challenges and seeking and evaluating efficiency options that support a more team-based, functional approach.
COVID was the wake-up call. We were running out of blood. Prior to the pandemic, there was not mainstream awareness around a patient-centric approach to improving perioperative patient blood management. A greater awareness plus media exposure, combined with new publications and guidelines, have helped the medical society identify key areas of improvement in patient care, such as with acute bleeding management, which viscoelastic testing is best for.
The migration toward the point of care and advent of newer viscoelastic testing technologies, such as the Quantra from HemoSonics, ROTEM Sigma, or TEG 6s, which all offer unique features, differences, and optimizations, provide options that clinicians, laboratories, and extended caregivers can evaluate in the effort to become better, more functional health care teams.
Alberto Gomez, any company trying to offer a full line and a full solution now has a viscoelastic strategy within its product portfolio. Can you speak about what that is within Werfen?
Alberto Gomez, MBA, group product manager, hemostasis, worldwide marketing, Werfen: At Werfen, through our acquisitions of Tem and Accriva, we added a portfolio of point-of-care hemostasis testing systems, including ROTEM Sigma and Delta viscoelastic testing systems for bleeding management. So we absolutely have solutions across the continuum of hemostasis testing, from the laboratory to the point of care. This allows us to deliver fast and accurate results to the clinician, helping to ensure that patients receive the right care, when they need it. This also helps reduce downstream costs.
Eric Salazar, where are we with the adoption of viscoelastic testing in your mind and among your colleagues? Are we just beginning? Midway?
Eric Salazar, MD, PhD, clinical associate professor, University of Texas Health San Antonio: Viscoelastic testing is here to stay. It’s probably more available in larger, more academic labs. Some smaller community hospitals might not have viscoelastic testing just yet, but that’s changing; there’s more adoption.
The burden is on pathologists to educate clinicians on when and in which clinical scenarios viscoelastic testing can and should be used. For example, can you use viscoelastic testing to guide blood product transfusion in a bleeding patient? Yes, that’s a good use. Can you use viscoelastic testing to diagnose von Willebrand disease? Not right now.
The burden is also on pathologists to make sure we’re understanding viscoelastic testing from a regulatory and safety perspective. For example, viscoelastic testing is one of the only, if not the only, test in the lab in which you can view results developing in real time. A provider can be in the OR watching the patient’s TEG or ROTEM curves develop. What does that mean from a lab perspective? It means results are getting released. Forget interfaced discrete results—it’s already out there; there are no reviews. We have to be sure we make the results available but in the safest way possible. If something changes we should notify providers as quickly as possible. From the CAP Hemostasis and Thrombosis Committee, colleagues Geoffrey Wool and others worked on updating CAP standards to reflect viscoelastic testing’s differences relative to other coagulation tests.
At last year’s roundtable we discussed automation, not only because it’s desirable but because we have a shortage of expert laboratory staff, which one tends to associate with areas like thrombosis and hemostasis testing. And once we automate, do we do so within a dedicated workcell in coagulation or do we put coagulation testing inside the large core lab and total laboratory automation setup? Is that a fair characterization of what is still top of mind for your customers and potential customers?
Tara Simpson, MBA, product manager, Diagnostica Stago: Absolutely. We have seen a move toward automation in all our laboratories. There are laboratories that are hyperfocused on coagulation, where a dedicated system makes sense because of the volume of samples. Stago has the Sta WorkCell Max, a dedicated automated system run by our digital solution for coagulation, and that can be the answer for some sites. Other sites have automation lines throughout the lab. Because staffing is one of the biggest struggles, automation is the way folks are moving. Stago meets those needs also; you can put our analyzers directly on an automated line.
Jackie Hauser, are you seeing at Siemens Healthineers a trend toward wanting to put coagulation testing on an overall core laboratory line?
Jackie Hauser, MT(ASCP), senior marketing manager for hemostasis, Siemens Healthineers: Some customers want to put coagulation on a large, TLA-type line, and others, particularly those that may also want to run special coagulation laboratory testing, might want to consider a separate workcell. Our Aptio automation system has the capability to do either one. Although we’re not necessarily thought of as a workcell company, we can, with our Aptio system and Atellica Data Manager middleware and workflow IT systems, create workcells for customers. More and more customers are starting to think about that. It’s the trend in the industry now.
Lance Trewhella, in your role as a regional sales consultant, are you hearing from your customers and potential customers that they are thinking about the point-of-care solution as being relief for the workload at a core lab? In other words, as with so many other places in in vitro diagnostic testing, we like to see point of care combined with core laboratory efficiency.
Lance Trewhella, regional sales consultant, HemoSonics: Yes and no. It goes in line with my experience with automation. When I was an administrative laboratory director, we put coag on the line. It was important to set expectations with end users and say, If we do this, you may experience an extended time on other results but improve efficiency.
I do see people wanting things quicker and trying to be more efficient. Point of care is great, but it’s important to narrow the group that will run it and make sure they’re efficient doing it.
My original training was as a nurse, and HemoSonics makes interpretations easy. Being able to explain to people in five minutes what products their patient needs was a game changer that led to my joining HemoSonics. The graphs are great for those of us who have been looking at them for 10-plus years—I can look at a ROTEM and TEG tracing and know what the patient needs—but for those who don’t do it every day, the point-of-care option is a game changer.
Dr. Volod, you and Dr. Salazar have the challenge of explaining special coagulation, the problem coagulation. How are you dealing with these special coagulation situations?
Dr. Volod (Cedars-Sinai): When I was a resident at Cedars-Sinai, the coagulation laboratory was separate from the core laboratory. Then a merger occurred and coagulation was brought in as part of the core laboratory. Special coag needs the expertise of a specially trained clinical laboratory scientist and they need to work closely with the pathologist so they release reliable results. For example, when they run factors and see a lupus coagulant or inhibitor effect, we need to look at and choose the results. When they run factor VIII inhibitor titers, it’s the role of the pathologist to choose which is the correct titer for the patient. We eventually moved out of the core laboratory and had special coag laboratories and special testing.
Now the issue is the need for 24/7 availability for a center that needs to run testing for a hemophilia patient who is expecting to have major surgery. The laboratory needs to run factors or von Willebrand factor 24/7, but that special laboratory is not open 24/7. Now I am working backward to try to validate some of those necessary tests to be performed at the core laboratory. So it’s a complex issue and it’s ongoing.
One area companies need to work with when they bring an assay onboard is the hospital’s IT security system. For example, Stago has great software for automating factor assays, but we could not bring it in-house because of our IT security system. They were not allowing us to accept that format. We are working with Stago on ways to bring it in-house because IT is worried patient information will be lost when it goes through the middleware.
Tara Simpson, would you like to comment? Hospital IT, like the lab, doesn’t have enough people and has a laundry list of things it needs to get done. I’m assuming you’re doing your best to help those hospital IT people integrate your systems into care?
Tara Simpson (Diagnostica Stago): Yes. Everyone on this call can speak to the importance of cybersecurity. We’ve been so focused on the patient and where we need to get the results, but we need to make sure the results are secure throughout the entire digital ecosystem. Cybersecurity in health care is a new realm.
Alberto Gomez, the laboratory, because it touches almost everywhere in the hospital, continues to be touched almost everywhere by hospital IT—the LIS, the middleware that’s dedicated to the instruments, the EHR, which you all have to integrate with, and then there’s cybersecurity on top of it. It’s a big challenge, isn’t it?
Alberto Gomez (Werfen): Yes, it’s certainly a challenge. Connectivity is a must. The majority of our customers have integrated networks, with oversight and connections required in many different locations and security is essential.
In the past, we could install a solution first and then speak with IT administration. Now it’s the other way around: We start with IT administration, determine what they need, and then look at how our solution can be optimized for them. The conversation has changed radically.
Dr. Salazar, in our discussion last year we raised the question about the need to have reflex testing built into all the testing strategies in thrombosis and hemostasis. Is there still that need? And what have you done in the past year to make reflex testing easier at your place and others?
Dr. Salazar (UT Health): Reflex testing in the coagulation laboratory plays a critical role because it allows clinicians to order a test that leads to a cascade of other tests, if there’s a clinical need or the results indicate those tests should be done. The benefits of that include limiting unnecessary tests. You don’t have to run a full panel if you don’t have to run a full panel. A good example is lupus anticoagulant testing, where you might run an initial screen and then do reflex testing depending on the results.
In terms of tying this back to automation, one good way to do that gets at the role of middleware or the LIS in the whole automation process. There are many different levels of automation. One level might be the device itself, automating and running a particular test on an automated platform. But it can also mean software-supported automation, like middleware, that helps us build rules to allow for reflex testing. Dr. Volod mentioned a good example of this—running factors. Sometimes factor results require that we run additional dilutions. For a less experienced technologist on the night shift or a technologist who doesn’t do it every day, deciding whether to run additional dilutions may be difficult; you have to follow a lot of rules. Middleware or rules that are built in can help automate those decisions and can standardize and help with training.
I want more help with automating the more esoteric types of tests that have an acute need and that are more manual, more difficult to implement in a special coag lab. Heparin-induced thrombocytopenia antibody testing is a good example—it used to be a manual ELISA that took hours to run. We now have automated solutions for that. I’m hopeful that other esoteric tests, like an ADAMTS13, get automated options. Why do we want this? One is the benefits of automation that we already know. The other is that if a manufacturer released those types of tests on an automated platform, it might no longer be a laboratory-developed test, and we all know the worry of labs across the country around LDT regulation. A lot of special coag, esoteric coag can be LDT. It would be great to have more automation along these lines to help us mitigate the need for LDTs.
Alberto Gomez, tell us about automating and putting into kit form esoteric coag assays that were otherwise in the realm of the LDT.
Alberto Gomez (Werfen): Both our ACL AcuStar system and our new ACL Top 970 CL, which we recently launched in Europe, feature automated chemiluminescence. This allows us to offer very specialized assays, such as heparin-induced thrombocytopenia IgG, antiphospholipid syndrome for lupus anticoagulants, and others, available 24/7. This has changed the diagnostic workflow, thus improving patient care.
Additionally, we see global demand for middleware to support the management and creation of more complex testing algorithms. Initially we offered simple rules on our systems. But our customers needed more; it’s not enough to say, If this result, do this. They need sophisticated solutions to create complex algorithms and ensure quality and compliance. Our HemoHub data manager provides all of this.
Jackie Hauser, can you comment on the need for manufacturers to do more on the esoteric end to make tests available?
Jackie Hauser (Siemens Healthineers): Some of the assays that have been mentioned are ones that companies are looking at to bring to market. The automation of these assays with the middleware to make decisions easier is the most important thing happening now. We’re seeing it across the board—people are relying more on having the special testing of coag done in a more automated, standardized way because of rules. Those are the rules their pathologists want to put into place. Manufacturers have to be adaptable to rule sets and the ways special coag labs want to operate.
We can’t talk about coag testing without talking about D-dimer. Last year we talked about it being a big hero during the pandemic. Dr. Volod, is D-dimer still underused or has it found its niche?
Dr. Volod (Cedars-Sinai): Nowadays it’s an instrumental part of every laboratory. Teamwork is part of bringing any assay onboard, and D-dimer is a good example. The emergency department a couple years ago reached out to me and said they needed an age-adjusted D-dimer assay as soon as possible and we should consider switching to that type of testing. But the laboratory cannot just switch; we must ensure the assays we run are the best quality. I reviewed all the literature on age-adjusted D-dimer that used the same type of assay we run. To validate age-adjusted D-dimer would be impossible even in other large institutions, so I have to rely on the literature. We’ve since changed to age-adjusted D-dimer. I asked the clinicians how they perceive it, do they use it, are they overusing or using it appropriately, and they’re extremely happy that we changed.
When I served on the CAP Hemostasis and Thrombosis Committee, we wrote an article on the appropriate use of age-adjusted D-dimers because laboratories wanted to accept them without understanding what they were running and how they will run it [https://bit.ly/D-dimer_032017].
Dr. Salazar, tell us where D-dimer is now and what you’re doing with age adjustment for D-dimer.
Dr. Salazar (UT Health): D-dimer is widely automated, but there continue to be problems with D-dimer testing. One problem is the comparability of D-dimer results. What units do you result in? Is it DDU [D-dimer units] or FEU [fibrinogen equivalent units]? If it’s DDU or FEU, is it milligrams per liter or nanograms per liter? The literature is full of examples in which the units are not indicated for the D-dimer results, so we don’t know what’s being reported.
As with point-of-care assays, we have to be sure our D-dimer assays are being used appropriately. We want to be sure about this in the literature and in clinical use. Is the D-dimer assay labeled for exclusion of venous thromboembolism or to be used to aid in the diagnosis of venous thromboembolism? Depending on how it’s labeled, we have to make sure our clinicians are using it appropriately. The burden is on pathologists to educate clinicians about the tests we run in our lab. The CAP committee continues to work on addressing these various issues around D-dimer testing.
Would anyone like to raise a question or a topic we haven’t addressed?
Jeff Light (HemoSonics): We’re seeing unsolicited interest in using viscoelastic testing in areas that aren’t yet indicated. I am interested in hearing comments on that because there doesn’t seem to be a consensus among laboratories on how to approach it.
Dr. Volod, can you comment on developing laboratory-developed tests out of viscoelastic testing methods in your laboratory?
Dr. Volod (Cedars-Sinai): I’m working on this with my team because it requires an extra validation process, extra runs. I’m receiving numerous requests from the OB-GYN team for point-of-care tests because having an assay in the laboratory is not good enough for a patient who can bleed liters of blood in a minute. By the time we get results to them, it’s already not representing the current status of the patient.
There are no FDA-approved viscoelastic assays for OB-GYN. We are looking at bringing the Quantra hemostasis analyzer into the OB-GYN OR to do it as a laboratory-developed test. But it’s the role of the laboratory director to speak with the team to understand the needs of clinicians. We cannot prevent clinicians from sending an assay to the laboratory. For example, let’s say a viscoelastic assay for OB-GYN is not validated but a clinician sends it. We have to run the assay. We can’t say we will accept this specimen and reject another specimen. In certain circumstances, I saw the benefit of having the results available even though it was not approved. I discussed the results with the clinician and explained there is a limitation and even so, it does show it’s not approved and it’s their responsibility to act on it. I’m willing to take extra steps to bring an assay onboard if I see there is a use and need for it, including for viscoelastic assays.
Dr. Salazar, can you reply to that same question?
Dr. Salazar (UT Health): There’s a lack of education of our clinical colleagues on what the regulatory requirements are around viscoelastic testing and in which patients it’s allowed to be used on label and prevent us from going into the LDT realm.
I get the feeling that our clinical colleagues, broadly defined, including anesthesiologists, surgeons, perfusionists, respiratory therapists, ECMO specialists, don’t always hear that message. Often the first line of messaging is not coming from the pathologist; it’s coming from industry, from a representative of a manufacturer.
We have to be careful about the way we talk about the use of viscoelastic testing and LDTs. That’s why I mentioned it initially: Can we use viscoelastic testing to guide blood product transfusion? Yes. Can you use it to diagnose von Willebrand disease? No. I’m not sure that thinking is widely understood, so we have to educate folks on the limits. It’s like a point-of-care test to some extent. Results can be an excellent guide if you understand the limits of sensitivity and specificity. Can you use it to diagnose a particular disease? Usually, no. You have to do more specific and sensitive coagulation testing to get at that diagnosis.
Do we have enough resources in our laboratories to make sure it develops properly? I say this because of the shortage of pathologists. How are we going to interest pathologists in training to dedicate themselves to a field as complex as coagulation and thrombosis and to the education of others that it requires?
Tara Simpson (Diagnostica Stago): The onus is on us as your partner on the industry side. We have to find out what you need and understand the challenges you face. It is on us to learn more and help create excitement around coagulation, the world of viscoelasticity, and hemostasis as a whole. We’re doing that through education, advertisement, and reaching out through laboratory societies and other avenues.
Alberto Gomez (Werfen): We will continue to support laboratorians and clinicians with automated solutions and education via our Werfen Academy e-learning platform. This combination increases awareness and the ability to perform essential testing, previously considered esoteric, in central laboratories.
Jeff Light (HemoSonics): We need to focus more on earlier education, not only for pathologists but also for clinical teams, residents, and other disciplines. This way, when they come up against the coagulation issue, we can start the conversation on a higher level. For viscoelastic testing, we need health care and industry to work together to lower the barrier to entry and allow access to, and understanding of, time-critical diagnostics with insight based on good science and good clinical understanding.
Lance Trewhella (HemoSonics): The conversation needs to start in the lab, especially for the LDT questions. Education is key. I spent more than 10 years at an academic medical center in Rochester, Minnesota, and educating residents who are coming in that first year, getting them exposure to transfusion medicine and coagulation, and creating a partnership early on are key, as is getting exposure to viscoelastic testing from all the different manufacturers early.
On the topic of cybersecurity, the Cybersecurity and Infrastructure Security Agency just released its mitigation guide; it’s a good resource for the health care industry and hospitals [https://bit.ly/CISA-guide].
Jackie Hauser (Siemens Healthineers): It’s all about education and our partnership as vendors with your institutions to provide information and education not only for the technologists but also for pathologists coming onboard.
At this year’s International Society on Thrombosis and Haemostasis meeting, I saw a lot of newer, younger faces, so I think there is excitement from the next generation of pathologists to do coagulation and coagulation testing.
Dr. Volod and Dr. Salazar, how can the vendors help you? What do you need from them?
Dr. Volod (Cedars-Sinai): I’ve had the pleasure of working with each of the companies on different types of tests and we have a great professional relationship. For example, when we brought TEG in-house, initially I was giving lectures with a representative from Haemonetics to surgeons and clinicians, but I didn’t have time to give thousands of talks. Haemonetics continued the education to nurses, clinicians, and anesthesiologists. Same with HemoSonics with the Quantra. They have wonderful clinical specialists who help with validation, education, and troubleshooting.
The companies have excellent clinical teams. There is a sales team but also a clinical team, and that team is composed of nurses. Not only are they great resources but they speak the same language—perfusionists speak with perfusionists; nurses speak with nurses. The companies also provide webinars. It reduces the volume of work for the lab so we can work on bringing assays in-house for viscoelastic and coagulation testing.
Dr. Salazar (UT Health): From a tangible perspective, it’s continuing to build trust and have open lines of communication. If a vendor notices that clinical colleagues at a particular site have a large number of questions, the vendor can make them aware that a pathologist is available to serve as a resource for those types of questions.
Coagulation, in terms of medical education, is a field that doesn’t usually have a dedicated fellowship. It’s folded into other training mechanisms, whether it’s hematopathology or transfusion medicine or others. As the complexity continues to grow, it might be rising to a level of our needing to identify, for the future, defined pathways of pathologist education.