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Anne Paxton
October 2024—Werfen launched in July its Gem Premier 7000 with iQM3 blood gas testing system that for the first time makes hemolysis detection possible at the point of care.
“Not having the capability to detect hemolysis at the point of care has been a gap in the field for quite a long time,” says Heather Stieglitz, PhD, D(ABCC), co-director of clinical chemistry and toxicology at Ohio State University Wexner Medical Center and clinical assistant professor, Department of Pathology, Ohio State University College of Medicine.
There was no way to detect if potassium results at the point of care, whether high or low or normal, were affected by that preanalytic error, she says. If a physician or other point-of-care testing user noticed a result that didn’t fit with the clinical picture, they might question the result and recollect the sample. “But unless the user thought the result was outside the realm of possibility,” Dr. Stieglitz says, “it was accepted and we didn’t have any way of flagging the result to say, ‘This specimen is hemolyzed.’” Dr. Stieglitz is medical director for point-of-care testing at five of the medical center’s outpatient services sites. Her laboratory has five of the new Gem Premier 7000 systems.
Alan H.B. Wu, PhD, co-core laboratory director at Zuckerberg San Francisco General Hospital, says: “Most laboratorians who oversee whole blood electrolyte testing know this is a problem but are unable to do anything about it. It’s sort of like the elephant in the room. While it’s obvious to laboratorians, it is not openly discussed because that would highlight a deficiency.”
With Werfen’s new system, hemolysis detection is based on acoustofluidic technology for plasma separation, combined with photometric determination. Intelligent Quality Management 3, or iQM3, provides real-time, automated, and continuous assurance of sample quality across the most common preanalytic errors, Werfen says, including hemolysis, micro-clots, bubbles, and lipemia. The Food and Drug Administration cleared the system in 2023.
It was the laboratory community that pressed for a solution, says Kristina Powell, Werfen’s director of acute care diagnostics marketing. “Around the world, laboratories have been explicitly saying, ‘We’ve been talking about the problem of hemolysis for many years. It’s time for solutions and no one is solving it. Have this problem solved.’ And that’s what we did.” It made sense to target the blood gas analyzer, Powell says, because “every hospital has a blood gas analyzer and may be using it for potassium results that could be compromised.”
Hemolysis can falsely increase potassium measurements. “So you could potentially treat a patient for hyperkalemia who has normal potassium,” Dr. Stieglitz says. “Or you could potentially miss a hypokalemic situation because the result might appear normal when in fact it’s low. Those are probably the two most dangerous situations.”
Potassium is one of the OSU laboratory’s most commonly performed tests, she notes. But “the vast majority of our potassium tests are performed in a centralized laboratory on a chemistry platform that has the capability to detect hemolysis.” Hemolysis detection has been a point-of-care problem.
How many clinicians know the capabilities of the different instruments is unclear, Dr. Stieglitz says. “I don’t think many clinicians are aware they are getting a potassium measurement performed by blood gas analyzers that do not have the capability to detect hemolysis.”
Detecting hemolysis and recollecting a sample is no guarantee the second sample won’t have the same problem, Dr. Stieglitz says. “Detection gives the opportunity for the person who collected the blood to try again to get a better sample. If they were drawing from a venous-access device, they may decide to try a straight venipuncture next time or try collecting from a different site.”
In the past, if there was enough concern about hemolyzed samples, some laboratorians would take the blood sample and centrifuge it, then run that sample on one of the chemistry instruments that could detect hemolysis, says Dr. Stieglitz, who has read published articles on this practice. However, she knows of no institution that is routinely doing that with all blood gas samples. “At my institution that would be unfeasible. It just could not happen, especially at the point of care.”
Hemolysis detection is a breakthrough in Werfen’s development of the Gem Premier 7000, Dr. Stieglitz says. “The quality management system in its previous testing system, Gem Premier 5000 with iQM2, included control solutions and various system checks. With iQM3, there is an added module that can detect hemolysis.”
Very high amounts of hemolysis can start to dilute a sodium measurement as well and potentially other analytes. “For the other blood gas analytes like pH, PaCO2, and PaO2, we really don’t have a good understanding of how hemolysis affects them. And part of that is because we haven’t been able to measure hemolysis in these types of blood samples prior to this instrument.”
This breakthrough will encourage competitors to develop a similar capability to detect hemolysis at the point of care, Dr. Stieglitz predicts. “Every other manufacturer that’s producing blood gas analyzers will need to hop on board. Any manufacturer that is developing or producing devices that can measure potassium should be thinking about ways to detect hemolysis.” Whether hospitals will have the capital to take advantage of the breakthrough is a separate issue, she notes.
Zuckerberg San Francisco General Hospital is a Gem Premier 5000 user and hasn’t yet purchased the Gem Premier 7000 with iQM3 system.
“You can’t just go to the grocery store and pay for it,” Dr. Wu says. “It requires capital equipment, it is more expensive, and it will require more training. There are dozens of things you have to do to make this happen.”
Then, too, what blood gas analyzers are optimal will be determined by each hospital’s floor layout and workflow. For example, he notes, while almost every hospital uses Abbott i-Stat, it is not necessarily for blood gas testing. “The i-Stat reader is handheld so you can bring it to a patient’s bedside. Each cartridge is single use. You add blood, insert the cartridge into the instrument, get a reading, then discard the cartridge.”
By contrast, Dr. Wu says, “Werfen’s Gem has a totally different kind of use cartridge. Once inserted, it can do testing for up to 31 days without removal.” The Gem instrument is about the size of a computer monitor and sits on the bench and is typically not moved. “Those are two approaches that are being used for point-of-care testing. One, bring the device to the patient, and the second, bring the sample to the device.” The choice depends on a preference of styles.
The benchtop analyzer enables additional analytical quality enhancements. “Benchtop point-of-care devices have the advantage over handheld testing devices of providing real-time within-analysis quality checks on a specimen-by-specimen basis, which is not available on handheld devices,” says Dr. Wu, who is also professor of laboratory medicine, University of California San Francisco School of Medicine.
An ED’s size and location will factor into the decision on which instruments to acquire. “Our ED is pretty central. We have a couple of bench-level instruments there, so you don’t have to walk far from any patient to get to the instrument. That’s why we’ve chosen to have a base benchtop instrument.” Very large EDs might decide differently. “Due to distances, it takes a few minutes to get from one end to another, so that the handheld i-Stat meter makes more sense.”
“The beauty of i-Stat is it can do several dozen different tasks,” Dr. Wu adds. But “there’s no question” that hemolysis is the No. 1 cause of preanalytic error.
“Right now,” he says, “none of the other vendors of blood gas analyzers have the hemolysis detection feature. So if you are a customer of theirs, you have two choices: Don’t perform hemolysis testing or switch to Werfen.”
In many cases, he says, switching will be impractical. “What will more likely happen is that these other companies will come up to speed in time. They’ll know this is needed and will have a program to copy that. So you come up with something slightly different to get around the Werfen patent, you submit it to the FDA, you do clinical trials. It takes money and time and effort—maybe two or three years.” But the other companies are likely already working on similar technology, he adds.
A useful feature of the Werfen system is that it flags hemolyzed results with an icon and customizable message, Dr. Wu says. “There are different levels of hemolysis, from zero to mild to moderate to severe. The more severe, the more interference there is, the darker the color, the bigger the problem. What Werfen has done is take the measurement of hemoglobin and put it into one of these bins; then it tells you what it means,” based on parameters the user sets.
Users can define what level they will consider mild, moderate, or severe because “Werfen is not going to mandate how to use this product,” he says. “A lot of labs are going to tailor those definitions to what they’re already doing in the central laboratory so it becomes the same. Then what you do with the information is also user-defined. So if you get a severe hemolysis rating, which is available in our central lab, you can also get it on the Gem 7000.”
In his laboratory, “If it is extreme hemolysis, we won’t report the result. We’ll say, ‘Sorry, you have to recollect because the error is too great.’” But other labs may decide they’re going to report it “and then have to figure out what that means.”
For potassium results, if the hemolysis is moderate or mild, he thinks labs will generally report it with a note saying, “It’s hemolyzed and the results are going to be affected; they’ll be slightly higher and it’s up to the ordering physician to decide what to do next.” The clinician’s options are to accept the result and estimate what the potassium should be, or to cancel the test and order a repeat draw to get a more accurate result. Unfortunately, the second sample might be hemolyzed too, Dr. Wu adds. “So it’s never simple.”
A delay in turnaround time, treatment, or discharge costs money, he notes. Phelan MP, et al., quantified the direct expenses associated with poor-quality preanalytic blood samples collected in the ED (Phelan MP, et al. J Appl Lab Med. 2021;6[6]:1607–1610). They included a range of costs—$600 to $3,000 per bed-hour and inflation adjusted from 1996 to 2020—informed by a review of the literature on the topic and a range of hemolysis incidence based on previously reported data. Their finding: For an ED with 100,000 annual visits, a 40 percent draw rate for routine chemistries (including potassium), and a 10 percent hemolysis incidence, the direct cost impact of hemolysis waste is about $4 million per year as a result of the one hour of added length of stay on average for a patient with a hemolyzed blood sample.
An additional consideration should be the medical consequences of having to make decisions based on an inaccurate laboratory result, and those are harder to measure, Dr. Wu says. “How much sicker is a person going to be?” Or because you didn’t do a retest, “did you create a medical problem because you did some treatment that wasn’t necessary or indicated? Those are not as easily quantifiable as the turnaround time and length of stay, but they should be factored in.”
When a whole blood sample is inserted into the Gem Premier 7000 with iQM3, Werfen’s Powell says, “it’s able to isolate the plasma from the whole blood and then interrogate it automatically for the presence and quantity of hemolysis,” and then provide the user with information on the screen.
“It totally changes the paradigm from going blind to basically behaving like a sophisticated laboratory analyzer right there at the point of care.”
Like OSU, other early adopter sites have been using the new instrument this year. “Customers are very happy or completely ecstatic with the product,” Powell says. They all set out with a certain number of instruments, and the number grew as the months went by, she says. The Gem Premier 7000 system recently received in vitro diagnostic regulation clearance in Europe, where sales began in October, Powell says. Meanwhile, Werfen has plans for a worldwide presence. “We have a rollout plan for bringing regulatory clearance to the rest of the world, over the course of the next two years.”
Werfen does not view its new Gem Premier 7000 system as its last innovation in quality control. “As we continue to embed ourselves in the clinical settings with this technology, we’re going to learn a great deal,” Powell says. “We know that beyond in vitro hemolysis, which happens as a result of either how the sample is drawn or how it’s handled before it’s presented to the system, there are other types of hemolysis that are more specific to clinical treatment. With bypass or ECMO, for example, blood can be sheared when it’s passed through the mechanical circuit. This can impact the blood and result in hemolysis.” Addressing the full list of causes of hemolysis “can have a really positive impact on patient safety,” she says. “It goes beyond just the quality lab mindset. It transcends into the patient care paradigm, which is the most important part of the lab’s role.”
Says Dr. Stieglitz: “Hemolysis is an important preanalytical variable that’s definitely occurring in blood gas samples at the point of care, and we were not able to detect it before. Werfen’s is the first device that allows us to measure for that potential preanalytical variable in these samples.”
And as point-of-care programs continue to grow, she says, “the stakes of detecting hemolysis get ever higher.”
Anne Paxton is a writer and attorney in Seattle.