Things change; things stay the same. Not surprisingly then, and somewhat ironically, the factors driving innovation in routine hematology testing today are similar to the factors that have been driving innovations for the past few years: greater volumes and responsibilities, but fewer resources. Can you stand to hear “staff shortage” one more time?

“Five years ago, institutions in the medical world realized they were businesses and not charity organizations, and they’ve had to really defend budgets and absorb cuts year after year. When you never get the money you need, you have to do something to survive. The change was scary, but once we realized what the principals of the business were, we started moving,” says Steven DeVine, chief technologist of hematology at The University of Texas Medical Branch in Galveston.

Innovations brought automation to the lab: analyzers that technologists could walk away from and trust they would produce accurate results. The benefits were evident: faster turnarounds, more productive workforces, fewer errors, and perhaps a tiny bit less worry about the crisis in staffing.

But laboratory testing volumes have continued to increase, while the staffing crisis has worsened. The aging population has contributed to greater numbers of testing specimens, and so too have new tests. Some laboratories that have managed to increase efficiency have added volume through new, revenue-generating business ventures.

“There is a big demand in the lab to become more efficient, producing better turnaround times and doing more work with fewer people,” says Robert Miller, automated laboratory supervisor for Strong Memorial Hospital in Rochester, NY. With growing specimen volumes from outside the hospital, the lab continues to see its testing numbers rise. Miller cites automation as key to managing the workload.

“The only way we’ve been able to deal with the thousands of samples coming in to the lab every day is through automation. A lot of vendors have responded with better systems, and there are many automated lines you can use to make the lab more efficient,” Miller says.

The competition doesn’t hurt innovation either, notes Patricia Mullenix, MT(ASCP)SH, hematology and satellite labs technical manager at Memorial Health University Medical Center in Savannah, Ga. Increased competition spurs companies to create products honed to meet the demands of the marketplace. With compliance a moving target, regulations can also push innovation.

Naturally, many of the lauded advances in routine hematology testing involve electronic intervention. New or advanced automation in the areas of preanalytics, decision making, autoverification, quality management, coagulation, flow cytometry, point of care, and telepathology are having a positive impact in the lab. But basics can also be advanced: new cell stains, new tubes, and even new tests are pushing the field.

Automating Preanalytics
“The biggest improvement was when the hematology vendors started producing conveyor-type systems, where you load the tubes on at the beginning and get results at the end,” DeVine says.

Abbott Diagnostics Inc (Abbott Park, Ill) estimates that the preanalytic stage represents 65% of the laboratory workflow. Automated systems that handle preanalytics have been seen to further improve turnaround times and reduce errors. The fewer times a tube is touched, the fewer chances there are for mistakes to be introduced.

Beckman Coulter claims up to 80% of manual processing sample steps can be eliminated with its automated system, including sample receiving; sample sorting and prioritization; integrated centrifugation; sample decapping; aliquoting from primary tubes; loading and unloading of instruments from multiple vendors; the recapping of samples after analysis; the transfer of samples to refrigerated stockyards; and automated reflex testing, rerun, and repeat testing.

These tasks are often repetitive and very routine. Replacing the human arm with the robotic arm increases technologist safety, reducing infectious exposure and repetitive stress injuries. Bayer’s ADVIA centrifuge and decapper module can process 240 samples per hour with a 15-minute cycle time.

Brain to Brain
More of those samples are able to move through the line without manual interference at all. Automated lines have become—well—automated lines. Samples are input and automatically sent to the necessary analyzer(s); results are output. More instruments are able to integrate into line systems, and more are able to handle larger volumes with greater accuracy.

The flexibility means that laboratories can configure systems to match their specific requirements. “There are different ways to go with it, and that flexibility is good because each operation can tailor a system to its needs,” Miller says.

“The advent of robotic sampling allows specimen loading away from the analyzers and sometimes in conjunction with chemistry. The combination of hematology and chemistry has been rare but is changing. It’s starting to catch fire,” DeVine says.

Miller’s Strong Memorial lab incorporates both hematology and chemistry testing in the same lab, but separate work cells. With the installation of new instruments, it could add coagulation to the chemistry line. “We are transitioning to Diagnostica Stago [based in Ansinières sur Siene, France] instruments and could integrate them with our line,” Miller says.

Bringing Coagulation on the Line
Adding coagulation testing to a line can mean less work for technologists, particularly as the number of coagulation tests increase. “There are more and more new coag tests coming out to keep up with the changes in coagulation therapy,” says Miller, citing tests related to treatment with low-molecular-weight heparin or Factor 5 Leiden as examples.

Diagnostica Stago’s STA-R Evolution is the company’s line-ready coagulation instrument. Its test menu includes prothrombin time (PT); activated partial thromboplastin time (aPTT); fibrinogen; D-dimer; thrombin time; reptilase time; factors II, V, VII, VIII, IX, X, XI, and XII; protein C and S activity; protein C chromogenic; heparin, UFH; heparin, LMWH; AT III activity and antigen; plasminogen; antiplasmin; total and free protein S antigen; vWF antigen; and lupus assay (PTT-LA). Heparin cofactor II, DRVV screening and confirmation, and fibrin monomer are tests the company expects to be available soon. The instrument has an onboard capacity of 200 samples.

Better Analytics
Coagulation instruments are not the only ones expanding capabilities. Almost any instrument on the hematology line is incorporating innovations. “We started off with automation of CBC, RBC, and differential analysis. We added a track line and then reticulocyte counts and nRBCs [nucleated red blood counts]. Then the analysis got better. We are now looking at adding our DM96 to the line,” DeVine says.

The CellaVision DM96 is an automated digital cell morphology and informatics system from Sysmex Corp. The system preclassifies white blood cells and precharacterizes red blood cell (RBC) morphology; it is able to process 30 to 60 slides per hour and can load up to 96 at once. The system allows comparison of cell classes side by side and can be used to quickly scan slides and locate questionable cells. “The DM96 has given us real potential for time savings,” DeVine says.

Miller notes that instrument upgrades have reduced the number of differentials done manually in his lab, and that the lab is looking to upgrade again soon.

Mullenix’s laboratory uses Bayer instrumentation for automated cell counting and differentials. The company’s ADVIA 120 Hematology System has a fixed throughput of 120 CBC/diff samples per hour, delivering results for CBC, a five-part differential, platelets, and reticulocytes. The system can also deliver similar information for CSF [cerebral spinal fluids], one of the first companies to do so. Reportable CSF results include the white blood cell (WBC), RBC, and a differential that includes neutrophils, lymphocytes, monocytes, and eosinophils.

Mullenix has found that the Bayer instrumentation handles clear and colorless liquids well, but suggests that no one has body fluid examination perfect yet. “But they are close,” she says.

“Five-part differential counting systems are more elaborate and far more accurate then in years past because of the advent of software that can do scattergrams and look at white blood cells in different quadrants,” says Steven Galante, vice president of marketing and sales with NERL Diagnostics.

Multifunction machines are becoming more common. “We are seeing analyzers envisioned as more than just cell counters. Everyone is looking for an edge up, so the more value an analyzer can give to a physician or hospital, the better,” Galante says. This includes not only CSF analysis but also flow cytometry, particularly with regard to immunology. “One manufacturer has combined serology with cell counts,” Galante says.

Mullenix concurs, saying, “Flow cytometry is expected to be added to some instruments for basic flow markers, such as T-helper cells and CD61 for platelets.”

“Certainly, major medical centers will find cytology useful as part of a package, but costs may limit such instrumentation to larger institutions,” Galante says.

Automating Quality
Generally, this is the case with most innovations. New, expensive machines are first adopted by large institutions, and eventually, as the technology matures, the instruments become accessible to smaller facilities. Computerized management systems followed this pattern, but now most facilities, if not all, have some type of laboratory information system (LIS). These systems can feature decision-making capabilities and quality-management tools. In some laboratories, the LIS integrates with a larger enterprisewide program, such as an electronic medical record. Middleware is playing an increasingly important role.

“Middleware is crucial to automate decision processes. There are lots of decisions that are made; for instance, if you get this instrument flag, what do you do? If you get it in combination with another flag, what do you do? We have a five-page flowchart that our technologists can either refer to or memorize for help with this process. But systems are getting good at performing this work now, and there are packages that can be customized to tell the technologist what to do when something specific happens,” Mullenix says. She notes that these programs are both expanding and becoming more instrument specific.

Miller cites similar benefits in his lab. “The big innovation we were able to do was autoverification of hematology results. We built in an algorithm for determining when differentials need to be done. We are now able to use the flags off the analyzer, inputting that information into the LIS to make decisions regarding whether we need to do differentials. With improved flow cytometry and better algorithms, we were able to improve,” Miller says.

Even more exciting is remote viewing of slides, or telepathology. Miller cites the CellaVision DM96 as one instrument that offers this capability. “The analyzer reads the blood smears and displays them on a computer screen, which it then uses to produce a rough differential that the technologists review. Some laboratories are going that route — the technologists don’t have to look through the microscope the entire time,” Miller says.

Better ergonomics are just one benefit. Miller notes that the system can also help with staffing issues; a newer technologist can send slides to a more experienced colleague for review. Ironically, technologist expertise becomes more important with greater automation of differentials; those differentials that need to be done manually are more difficult.

Tina Dackemark Lawesson, CellaVision’s marketing communications manager, says that technological developments, including the development of hard-disk drives, TCP/IP communication protocol, and the development of standardized database formats have contributed to this capability. “The ability to store images over a long period of time in a database in conjunction with remote access opens up completely new ways of handling manual differentials,” she says. Storing patient slides as images means not only is remote viewing possible, but patient histories are easier to access.

Like telepathology, point-of-care (POC) cell counters are expected to be a new trend, but this equipment is still primarily in development. “There are companies developing waived hematology counts on either handheld analyzers or small benchtop instruments, and when they are commercialized, it will revolutionize how many do cell counting at the physician level,” Galante says. A waived test will mean that physicians will be able to conduct these tests in-house, with far speedier turnaround times.

Galante also expects coagulation to develop further POC testing systems. A number of systems to assist with coagulation monitoring are available today from companies such as Axis-Shield, HemoSense Inc, and Roche Diagnostics.

Bettering the Basics
Of course, it’s not all about automation. Some of the basics are undergoing change, too. Mullenix expects instruments to not only continue to get smaller, but to require less reagent and smaller sample sizes. More efficient reagent packaging will suit environmental concerns.

Galante adds that environmental concerns have affected reagents themselves. “Most of the reagent manufacturers have moved away from chemicals that harm the environment, such as azides. These cost more up front, but less overall since you do not have to worry about disposal,” Galante says.

Stains are evolving as well. Barry Stokes, PhD, senior scientist at Wescor, notes the company’s newest stain system employs a technology that gets around the limitations of aqueous space stains. “The new system features centrifugal staining where the reagents are sprayed onto the slide. The high concentration of methanol is evaporated rather than diluted, and the stain mimics Wright Giemsa or May Grunwald Giemsa,” Stokes says. He adds that the instrument is programmable and the stains are customizable.

There may even come a day when the tubes change. The industry has gotten used to the rainbow of blood tubes (lavender for hematology, blue for coagulation, red for chemistry, and so on), but Galante notes that some in the industry would like to see all analyzers on one line using one tube. “You would be able to perform 10 tests off one sample. In the past, the industry talked about chematology but was unable to develop a tube that could hold a sample for both electrolytes and CBCs,” he says.

Now, Galante says, the industry is starting with the test to see if the tube fits, rather than making a tube to fit the tests. He notes that this approach has led to the discovery that the lavender tube will also work for A1C testing. For laboratories that combine hematology and chemistry, advances such as this could provide benefits tied to turnaround, safety, and patient care.

“Pretty much anything that will save time is an innovation. We want to eliminate the routines so technologists can use their minds to deal with results rather than use their bodies to handle the manual operation,” DeVine says. The more things change, the more they stay the same.

Renee DiIulio is a contributing writer for Clinical Lab Products.

All in a Day’s Work
The complete blood count (CBC) test is so routine that it has become a staple of medical comedies and dramas on television.

Routine hematology testing also includes:
• White cell differentials;
• Reticulocyte counts;
• Platelet counts; and
• Erythrocyte sedimentation rate (ESR).

Special hematology testing can include:
• Bone marrow biopsies;
• Erythropoietin;
• Hemoglobin electrophoresis; and
• Protein electrophoresis.

Routine coagulation, which often falls under the purview of the hematology lab, includes:
• Prothrombin time;
• Partial thromboplastin time;
• Fibrinogen; and
• Fibrin split products.

Special coagulation tests may include:
• Clotting factor assays;
• Antigen-presenting cell resistance;
• Anticoagulant monitoring; and
• Lupus anticoagulant.

The hematology lab also tends to handle body fluids, including CSF counts and urinalysis. —RD