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Hematology roundtable: rules, reference ranges, POC testing

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November 2018—Reference intervals, point-of-care testing, the use of rules for efficiency, and the display of results in patient records. That and more is what a panel of experts weighed in on when CAP TODAY publisher Bob McGonnagle assembled them in September to talk about hematology instrumentation. What they told us follows.

Members of the panel were Parul Bhargava, MD, of the University of California San Francisco; Tracy George, MD, of the University of Utah and ARUP Laboratories; Dylan Camfield of TriCore Reference Laboratories; Danette Godfrey and Brian Riley of Sysmex; and Matt Rhyner, PhD, MBA, of Beckman Coulter. McGonnagle spoke too with Krista Curcio of Roche Diagnostics about the end-of-year launch of the m 511 instrument and more. See Hematology analyzers product guide.

What are two or three of the questions or problems or dilemmas you’re facing in the world of hematology instrumentation or hematopathology that are current concerns for you and your laboratory staff and for the clinicians and patients you’re serving?

Dr. Bhargava

Parul Bhargava, MD, professor of clinical laboratory medicine and director of clinical laboratories, Moffitt-Long Hospital, University of California San Francisco: A big issue we face in the hematology laboratory is building appropriate flagging rules to make sure the instrument serves our population appropriately. As medical director, I want to ensure a good balance between sensitivity and specificity; put in other words, rules should be sensitive enough such that all clinically significant abnormalities are flagged, yet should not be overly sensitive for our population, creating unnecessary manual reviews. Technologist time is probably our most precious commodity, and we need to create efficiencies to allow best use of their time. Another challenge is an ever-increasing demand, by clinical services, for shorter turnaround times and in some situations point-of-care testing.

Another issue facing the world of hematology at large is instrument calibrations and traceability. Having looked at a lot of proficiency testing data, I am struck by significant differences across platforms in some parameters, including, for example, the MCV. While there are significant differences in what different laboratories/platforms report for the same analyte, it is well known that individual reference ranges in many laboratories are often taken from published data validated internally using a small sample size. Thus while reference intervals for CBC parameters tend to overlap significantly across laboratories, there is more variability in instrument output.

Dylan Camfield, hematology technical specialist, TriCore Reference Laboratories: Point-of-care testing is definitely a priority in our system. We have numerous branch laboratories that are staffed by clinical laboratory assistants who do not perform high-complexity testing, so we have struggled in the past to find instruments that perform CBC and partial differential analyses that our staff could positively result and won’t be abnormally or excessively flagged for review. We still face that challenge with our existing instrumentation at the branch laboratories with the smaller Sysmex instruments; the majority of the flags indicate a possible corrective action, a peripheral smear review, which they can’t do at that location. At that point, they will release results that are not flagged and then reorder a stat sample to be sent to the core reference laboratory for confirmatory analysis.

I believe Sysmex now has new, smaller-scale instrumentation that’s fully FDA approved as moderate complexity but includes a five-part differential. I’m still a little unfamiliar with this new line of smaller instrumentation. Currently at those smaller labs we are using only a three-part differential.

November 2018 Hematology Analyzers product guide

As far as the larger-scale instrumentation comparability among different platforms and their parameters, we found fairly good correlation when we switched between vendors. We had to make only a few minor changes in our reference ranges, and we did that based off a large patient population that we could pool for months at a time and for which we gathered thousands of patient samples.

We have found the use of middleware is productive in building rules that target any number of patients—outpatients, oncology patients, and so on—to minimize review rates and optimize the clinical results that are important to the targeted population.

Danette, can you tell us about the moderately complex Sysmex offering for a five-part differential?

Godfrey

Danette Godfrey, director of IVD product marketing, Sysmex: The new XN-L automated hematology analyzer provides a standardized result with our flagship XN series but for smaller-volume hematology laboratories, clinics, and physician office labs. It uses the same technology of the XN scalable automation, including a result for immature granulocyte on every sample. This extends standardization from the hospital and reference laboratory segment to the physician office lab segment. So the XN-L is the same technology that is experienced throughout the full-scalable automation series product line.

When you talk about these needs at the point of care, are you talking only about physician office labs and clinics, or are you talking about, say, infusion centers—we think of the qualification for chemotherapy and things of this nature? Tell me a little more about these locations you’re looking at.

Dylan Camfield (TriCore): For us it’s more of the physician-operated laboratories. These are outpatient clinics that perform stat testing, so it’s not so much the infusion-type clinics as well.

Tracy George, MD, professor of pathology, University of Utah, and executive director, clinical trials and pharmaDx, ARUP Laboratories: I’m at a large central reference laboratory and the issues there are the arrival of older samples: getting accurate results on those samples and reducing the number of false-positive flags—for example, platelet clumps, variant lymph-type flags.

Dr. George

The other issue I see is the pediatric reference range. Hematology instrument manufacturers have a lot of newer parameters that look exciting and potentially have a lot of clinical utility or have shown clinical utility in the literature, but making sure we have appropriate reference ranges in adults and children is still a challenge.

Each laboratory will have slightly different reference ranges they have validated or should have validated. It’s not uncommon to have a sample coming in because the patient is anemic, and then we run it in our laboratory and the patient is not anemic at all. And you wonder if the reference range, for example in the child, was not established appropriately for, say, hemoglobin. But there are newer parameters that people would like to use, and we do struggle with what the appropriate reference range is. It’s hard to even validate reference ranges in pediatrics; we don’t have a lot of healthy children, toddlers, or babies volunteering their blood.

Matt, what do you hear and see in the field from Beckman Coulter customers and potential customers, in particular on reference ranges? Is Beckman providing guidance on reference ranges on the instrumentation—or how do you go about addressing this problem?

Matt Rhyner, PhD, MBA, senior director of product management and global marketing for hematology, Beckman Coulter: From my perspective, there’s sort of a splitting of customer needs. One set of needs are those of the high-complexity core lab with high sample volumes where an automated instrument is needed that does high-complexity testing, minimizes the need for manual intervention, and adds more clinically relevant parameters and insights. That’s a lot different from what we’ve been talking about, which is the other end of the market that’s also growing—the smaller point-of-care, physician office lab-type devices that are moderate or low complexity and could be run without a certified lab technician, for example. It’s like a barbell effect on the market, where those two ends seem to be the ones that are growing and probably reflect broader health care changes.

In short, we are continually developing products. In April 2018, we launched internationally for the physician office lab market our DxH 520 series [CE marked and pending FDA clearance], which is a simple analyzer that does a five-part differential. On the high end, for emergency departments, we recently launched our Early Sepsis Indicator [CE marked and pending FDA clearance] and we’re working through regulatory clearances on that. We are committed to establishing detailed pediatric reference intervals for all our new instruments, so often we partner with third-party hospitals and labs that have access to samples. We collaborate with testing houses that specialize in pediatrics and work with them, and we have active studies underway.

Dr. Bhargava, I think it’s only fair that we note that pediatric reference ranges tend to be a problem for a wide array of analytes and this problem is not restricted to hematology. Do you agree?

Dr. Bhargava (UCSF): Yes, I do.

Brian, let me ask you about your colleague’s comment on the barbell effect on the market, because I know it affects the physicians as well. They too see a growing business at the high end—high volume, high complexity—and yet at the same time great demand for efficiency at the point of care, whether that be a clinic, a doctor’s office, or on the floor of a health care system in a specialized application. Is that how Sysmex sees this market shaping up?

Riley

Brian Riley, director of brand content and engagement strategy, Sysmex: We’re talking about the full scalability of the solution. The CLIA-waived market was a way to close that loop.

Danette Godfrey (Sysmex): We see the full picture, from the physician’s office laboratory, with the first CLIA-waived hematology analyzer with the 12-parameter CBC and three-part differential, to the full scalability of the hematology analyzers to full automation—the idea is to create those efficiencies for customers that has been so successful for Sysmex hematology to this point. The standardization and the same parameters, the same access to body fluid monitoring, is what makes Sysmex unique in the market for customers to meet the needs of various markets. Whether that’s an integrated health network or a reference laboratory or a POL, there’s a scalable solution.

Dr. Bhargava, beyond the minimizing of manual differentials, which is a big issue, what more is there to this need for rules?

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