Jan Hodnett, MS, MT(ASCP)

Improved instruments advance patient management

It started in the basement workroom of the Coulter’s Chicago home. According to company lore, Wallace Coulter developed the “Coulter Counter” in 1958 because he was dating a medical technologist who was often late because she had to finish manually counting WBCs and RBCs using a microscope. After waiting several times for her to finish counting all those cells he decided, “there’s got to be a better way.”

Now, of course, there is a much better way to count and identify cells, and laboratories spent about $650 million dollars on hematology products in 2000. Beckman Coulter still has the greatest U.S. market share, but Abbott, Roche and Bayer are all vying for position.

  • Diagnostic Advances
    WBC Differentiation, WBC Nonviable and IG Enumeration, Rectic, PLT, RBC Morphology, Optional Methodologies, Optical Fluorescence, etc.
  • Moving Averages QC Program
    x–B, Population Statistics, Parameters Involved
  • Flagging Criteria
    User-defined options, Result Value Flag Attachment, Multiple Parameter Flagging Logic
  • Reticulocytes
    IRF, Abnormal Population Flagging, Absolute and Corrected Retic Count
  • Linearity Range
    WBC, RBC,HGB, PLT, Dilution Capability
  • Substance Interference
    Lipemia, NRBCs, Icterus, Giant Platelets, Clumped Platelets, Hemolysis
  • Internal Rule System
    Auto Verification, Print Suppression, etc.
  • Instrument LIS Interface
    Unidirectional, Bidirectional, Host Query, other
  • User Training
    On/Off-Site, Software, Video
  • Software
    User Friendliness, Help Screens, On-Line Help, Upgrades
  • System Component Integration
    Slide Maker, Slide Stainer, Robotics, etc.
  • QC
    Upload/Download Method, QC fail auto alert/stop
  • Calibration
    Automated or Manual, Periodicity
  • Random Access Testing
    Yes or No, User-Defined Options
  • Sample Size
    µL in manual, automated, dilution
  • Modes of sample introduction
    Number, Dilution, Walk-Away, etc.
  • Efficiency
    Igs, NRBCs
  • 24-hr Stability
    CBC, Diff, Retic
  • Technical Support
    Tournaround Time, Toll-Free Number
  • LIS Integration
    Generic vs. Custom design
  • Throughput
    Number CBCD/hour
  • Tube Size Accommodations
    Adaptors, Racks, etc.
  • Maintenance
    Time Interval and Time Required
  • Service
    Local, Regional, Response Time
  • Instrument Downtime
    Scheduled, Unscheduled
  • Procedure Manual Format
    NCCLS Compliant
  • Number in Service
    Local, Regional, U.S.
  • Cost Quote
    Purchase, Lease, Package Discount, Service Contract, etc.
  • Reagent Composition/Cost Per Test
    Environmental Waste Recommendations, CBC; CBC/Diff; CBC/Diff/Retic; CBC/Retic; Retic
Adapted by CLP from Louisiana State University Health Sciences Center, Shreveport, Louisiana, and the University of Michigan Hospitals, Ann Arbor, Michigan

Abbreviations: CBCD – complete blood cell count differential; CV-coefficient of variation; IG – immature granulocyte; IRF – immature reticulocyte fraction; NRBC – nucleated red blood cell. PLT – platelet count; WBC – white blood cell count

The Coulter legacy lives on
Beckman Coulter of Fullerton, Calif., launched a new series of high-volume hematology systems in July at the American College of Clinical Chemistry meeting. “We put 100 percent effort into hematology and the laboratory,” said Mary Beth Johnson, product manager, High-volume Hematology Systems. The Coulter LH 700 series combines new hardware, software and reagents to eliminate manual presorting of samples and achieve more accurate test results.

Hematology instrument manufacturers have been working to decrease the review rate of samples, which slows down results and is inefficient. “Keeping the false positive rate down is important to all of the manufacturers and it certainly has been one of our goals, but you also have to make sure the false negative rate doesn’t go up,” said Naomi Culp, Ph.D., senior product manager. “One of the goals with the LH series was to cut down the number of manual interventions because a result was flagged. With the new AccuCount technology and faster computers processing the data, we’ve gone a long way in achieving that goal. We’ve increased the linearity of the white counts and the platelet counts, giving us wider dynamic linearity range,” said Culp. Johnson explained that white counts are linear to 400,000 and platelets are linear to 3 million, which is about 2 to 3 times that achieved previously.

In some institutions, hematology has moved into a core lab with chemistry. “There aren’t as many med techs now, which makes decision support or post-analytical decision support important. Now, users can program their own set of decision rules that decide whether a sample is normal and what needs to be done. There’s no guessing. We started decision rules with the GenS and we’ve taken it a step further with the LH and made them even easier to program,” said Culp.

Bayer is moving toward disease monitoring
Bayer Diagnostics’ market strength is in technology, according to Byron Hewett, vice president, marketing, Laboratory Testing Segment, Bayer Diagnostics, Tarrytown, N.Y. “Technology is a niche Bayer carved out in this market segment a number of years ago,” he said.

Bob Barca, director of marketing, Hematology, explained that with Bayer’s peroxidase staining for white cells and two-dimensional optical analysis for red cells, “we measure both the size and content of the red cells, retics and platelets.” Peroxidase staining, originally used in identifying leukemia, is done on every sample now for white cell analysis. “There is a wealth of information gathered during the analysis of one sample, yet analysis is done very quickly (120 samples/hour on the Advia 120),” said Barca.

Barca explained that for retic counts, Bayer instruments do more than just count the cells, they also determine if the retic is functional. “We can determine if the cell is a mature retic or a young one. The CHr measurement determines whether the cells being produced are functional and whether there is hemoglobin within those cells. If hemoglobin is not present, then something is preventing the bone marrow from producing healthy reticulocytes. It’s a means for getting information on the bone marrow erythropoietic cycle without doing a bone marrow biopsy,” said Barca. Hewett added, ”this is something we’re very excited about, because patients with anemia and those undergoing EPO treatment benefit from this analysis.”

Since platelets are measured in the red cell channel, the internal structure, as well as size, of the platelet is measured. Barca pointed out that the density of the platelet is indicative of its activity. “Platelet activation is a hot topic these days, and we have studies going on to assess whether a platelet is activated or not. Activated platelets have been associated with MI and appear before traditional monitoring tests such as troponin and CKMB, so this will have an impact on the management of cardiac patients in the ER. Results indicate that these measurements may be very useful for disease management or disease monitoring—and that’s where we’re going.”

Bayer is currently investigating the automation of CSF analysis. Their CSF test would identify not only the number of cells, but the cell type as well. “We can do this because of our broad linearity ranges. We also offer direct cytometry, which enables users to take the undiluted sample up into the flow cell, allowing the counting of more cells and an accurate differential on that type of sample,” said Barca.

In July 2001, Bayer introduced two new instruments, the Advia 70 and the Advia S60, that were designed for the mid-sized hospital. The Advia 70 does CBCs and a 5-part differential and the S60 is a mid-range semi-automated slide stainer, new for this market.

Abbott goes with the flow
Abbott Diagnostics’ MAPSS (Multi-Angle-Polarized-Scatter-Separation) technology is the “heart and soul of the WBC differential technology for the Cell-Dyn 4000, 3700 and 3200 instrumentation,” explained John Cieslewicz, marketing manager, Abbott Laboratories, Abbott Park, Ill. “The Cell-Dyn 4000 also incorporates two-dimensional optical platelet analysis and fluorescence detection, which has made flow cytometry routine in the hematology laboratory, evident with the launch of the CD61 as a platelet marker and most recently the CD3/4 and CD3/8 markers for HIV monitoring. The performance of the Cell-Dyn 4000 is comparable to that of flow cytometry analyzers, but analysis is done in a routine hematology laboratory.” Importantly, the throughput of the 4000 has not been tremendously impacted by the addition of CD61 or CD3/4 and CD3/8. Cieslewicz added, “the whole set of CD3/4, and CD3/8 markers takes eight minutes to run and it’s fully automated. There is no tech intervention or tube-top popping. Getting a result in eight minutes is pretty quick compared to the time it takes in a flow lab.” Kim Caple, commercial director, Hematology, Abbott Diagnostics offered the example of an HIV clinic, “being able to turn the result around while a patient is still in the clinic.” Cieslewicz explained that the Cell-Dyn 4000 has an argon laser, which gives it the capability to do flow cytometric tests using multi-color RNA, DNA fluorescence for monoclonal analysis. In the future, the argon laser may make it possible to analyze abnormal white cells detected during routine CBCs with markers such as the CD45, or the CD34 stem cell marker. Caple added that there is opportunity for improving differentials with the capability to identify blasts and bands and to further delineate red cell morphology. “Manufacturers seem to be focusing on both of those areas with the goal of further decreasing differentials,” she said.

In addition to focusing on automation leading to improved workflow efficiency, Abbott is looking at developing computerization and connectivity to get results where they are needed. Caple added that remote data transmission of results using wireless or web-based transmission of results to the doctor’s office is an industry trend and will eventually allow pathologists and hematologists to call up and review scatterplots away from the instrument.

Cieslewicz concluded, “Our technology is set up to take us into the future, better than ever. Just like the brain, we’ve only used about 10 percent of the MAPSS technology so far. “

Roche innovates
The emphasis at Roche, through its distribution of the Sysmex line, is on carving an innovative path in the hematology market — and their share of the market is rising. One emphasis at Roche is on systems: incorporating flow cytometers into routine analysis, connecting instruments with slide makers/stainers, linking to external systems (such as robotics specimen transport), and networking with work area subsystems, the LIS and HIS. Another emphasis is on incorporating flow cytometry into routine analysis.

The Sysmex XE-2100 incorporates fluorescent flow cytometry on the standard hematology platform, processing 150 samples per hour and simultaneously reporting 26 parameters while maintaining labor and cost efficiencies. Using advanced technology on each sample improves the early discovery of abnormalities that impact on patient health. According to Andy Hay, Sysmex Hematology Business Manager at Roche Diagnostics Corp., Indianapolis, Ind., “the most significant change in technology has been the increase in routine testing sensitivity affecting patient management in all areas of hospital care, including early diagnosis of leukemia, tumor management, infections, and the spectrum of hematology diagnoses.”

Interpreting cells, not just counting them
The hematology market is not growing much dollar-wise, but it is changing because of core labs and a shortage of trained personnel. Today’s hematology analyzers have to do more to compensate for that. Flow cytometry and computerization will allow better patient management and disease monitoring — a long way from just counting cells.