Hematology, bringing more options for laboratory professionals

The traditional concept of laboratory hematology will evolve into leveraging a variety of orthogonal techniques to produce deeper clinical insights faster and at a lower cost than ever before.

Manual methods of characterizing blood cells and blood components can be unreliable and labor-intensive. Re-processing samples and performing additional procedures, such as nucleated red blood cells and optical counting are often necessary to collect the data required for disease detection and monitoring. In addition, qualified laboratory technicians are increasing in age and less experienced technologists replacing them are yet to have sufficient training in multiple specializations and complex manual analyses, in order to address the labor requirements in multi-discipline laboratories. In contrast, fully automated hematology analyzers can accommodate a wide range of analyses, significantly minimizing manual intervention and human error.

Another advantage of utilizing hematology analyzers over traditional cell counting lies in their large-scale capacity. Hematology analyzers are capable of processing hundreds of samples simultaneously, making them ideal for high-throughput industrial, medical, and research applications. Sophisticated models with improved sensitivity can also detect not just blood cell and platelet count, but also the reticulocyte function and cell size.

Operated by advanced algorithms, modern hematology analyzers also implement data-fusion capabilities to integrate information from multiple separate modules and identify patterns, which cannot be determined by a singular module. This function leads to convenient detection and correction of interfering elements and lesser need for manual reviews.

These powerful instruments provide laboratory technicians with access to greater and more specific cell information for highly accurate CBC with differential and lower review rates. Hematology analyzers are crucial for streamlining lab processes and improving diagnostic testing. Like any other industry, hematology analyzers were also impacted by new developments in other areas, like introduction of laser, efficient pneumatic control, etc. This provided scope to manufacturers in reducing the size of analyzers and making them more efficient.

However, for a long time, focus was on making an efficient, robust, and user-friendly system. With new-age data informatics and science around algorithms, now focus is to also improve clinical utility, and exceed expectations.

Experience from hematology analyzers has also evolved greatly, and now the analyzer is helping in lot of morphology analyses than just being a cell counter. Aspirations have replaced expectations and the user is interested in what more can be achieved.

Hematology analyzers are capable of identifying the presence of abnormal cells, which eliminates the need to manually determine and review cells not within the supposed measurements. However, the reliability of a unit’s flagging system may differ, depending on the model, so it is advisable to check the system’s capability for flagging beforehand and assess the hematology analyzer in terms of sensitivity, specificity, and efficiency. In order to control the quality of your results, programmable models allow you to set range and measurements to flag cells, not within your specified limits.

Some automated hematology analyzers are equipped with 3D VCS technology to ensure accurate RBC analysis. This innovation is considered to deliver the highest sensitivity, specificity, and efficiency in terms of blood cell analysis. 3D VCS technology is capable of accurately characterizing the size and internal structure (including chemical composition) of a cell. Moreover, additional data like cellular granularity, nuclear lobularity, and cell surface structure are provided by 3D VCS technology.

Laboratories with low volume rely on 3-part differential analyzers, and busy laboratories with 5-part differential are gaining interest. The most relevant white blood cell types to count are the neutrophils and lymphocytes, which are quantified by a 3-part differential hematology analyzer (along with monocytes). Many clinics and smaller hospitals often use 3-part systems. 3-part hematology analyzer is the choice of many since it meets many basic requirements and also comes at a much lower price. However, specialty clinics and larger hospitals typically use 5-part analyzers, which are more precise and can perform complete blood counts. These types of hematology analyzers classify WBC intolymphocyte, monocyte, neutrophil cell, neosinocyte, and basicyte. Many 5-part hematology analyzers are also capable of higher sample quantities and automated sampling processes, which account for its higher price range.

New tools and parameters will continue to emerge as the market competition increases and technology evolves. Thus, the traditional concept of laboratory hematology will evolve into leveraging a variety of orthogonal techniques to produce deeper clinical insights faster and at a lower cost than ever before. Indeed, this is an exciting time in the field, and the coming years should see seismic changes that promise to bring better patient care and more options for laboratory professionals.

The pandemic has led to a renewed interest in robust, portable diagnostics. As point-of-care (POC) and at-home testing tools, CLIA has started to acknowledge novel technological advancements in blood diagnostics and waive-specific instruments for use outside of the lab. Some examples of these waivers include blood gas and hematology analyzers and molecular tests (e.g., influenza tests).

In addition, CLIA now offers individualized quality control plans (IQCP) that help leverage technological advancements in the industry, enabling a transition to greater reliance on instruments with novel internal controls. These systems contain sophisticated built-in mechanisms, sometimes referred to as electronic controls, that eliminate some of the traditional oversight and the need to run external controls.

One of these built-in mechanisms is imaging-based POC hematology, which uses imaging and artificial intelligence, or AI, to detect different interferences or failures that may compromise results.

As regulatory authorities and lab directors gain more confidence in these technologies and their internal quality control, assays should become more accessible outside the lab setting. This will provide more flexibility for healthcare providers in treating patients around the globe, from isolated rural areas to the center of bustling cities.

These developments will also reduce costs associated with maintaining highly regulated centralized laboratories and allow lab technicians to focus on the most complex diagnostic cases that require their full expertise.

Research Corner
A blood test developed at Washington University School of Medicine in St. Louis has proven highly accurate in detecting early signs of Alzheimer’s disease in a study involving nearly 500 patients from across three continents, providing further evidence that the test should be considered for routine screening and diagnosis. The study is available in the journal Neurology.

“Our study shows that the blood test provides a robust measure for detecting amyloid plaques, associated with Alzheimer’s disease, even among patients not yet experiencing cognitive declines,” said senior author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology.

“A blood test for Alzheimer’s provides a huge boost for Alzheimer’s research and diagnosis, drastically cutting the time and cost of identifying patients for clinical trials and spurring the development of new treatment options,” Bateman said. “As new drugs become available, a blood test could determine who might benefit from treatment, including those at very early stages of the disease.”

Developed by Bateman and colleagues, the blood test assesses whether amyloid plaques have begun accumulating in the brain, based on the ratio of the levels of the amyloid beta proteins Aβ42 and Aβ40 in the blood.

Researchers have long pursued a low-cost, easily accessible blood test for Alzheimer’s as an alternative to the expensive brain scans and invasive spinal taps now used to assess the presence and progression of the disease within the brain.

Evaluating the disease using PET brain scans – still the gold standard – requires a radioactive brain scan, at an average cost of USD 5000 to USD 8000 per scan. Another common test, which analyzes levels of amyloid-beta and tau protein in cerebrospinal fluid, costs about USD 1000 but requires a spinal tap process that some patients may be unwilling to endure.

This study estimates that prescreening with a USD 500 blood test could reduce by half both the cost and the time it takes to enroll patients in clinical trials that use PET scans. Screening with blood tests alone could be completed in less than six months and cut costs by tenfold or more, the study finds.

A commercial test based on Bateman’s research was certified in 2020 under the Clinical Laboratory Improvement Amendments (CLIA) program. The CLIA certification program is run by the Food and Drug Administration in partnership with the Centers for Disease Control and Prevention and the Centers for Medicare and Medicaid Services.

Known as Precivity AD, the commercial version of the test is marketed by C2N Diagnostics, a Washington University startup, founded by Bateman and his colleague David Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology. Bateman and Holtzman are inventors on a patent the university licensed to C2N.

CLIA certification makes the test available for doctors in the United States. It is intended to provide information that will aid the medical evaluation and care of patients who already have symptoms of cognitive decline. A similar certification makes the test available in Europe. The test is not yet covered by most health insurance.

The current study shows that the blood test remains highly accurate, even when performed in different labs following different protocols, and in different cohorts across three continents.

Scientists did not know if small differences in sampling methods, such as whether blood is collected after fasting or the type of anti-coagulant used in blood processing, could have a big impact on test accuracy because results are based on subtle shifts in amyloid beta protein levels in the blood. Differences that interfere with the precise measurement of these amyloid protein ratios could have triggered a false negative or positive result.

To confirm the test’s accuracy, researchers applied it to blood samples from individuals enrolled in ongoing Alzheimer’s studies in the United States, Australia, and Sweden, each of which uses different protocols for the processing of blood samples and related brain imaging.

Findings from this study confirmed that the Aβ42/Aβ40 blood test, using a high-precision immunoprecipitation mass spectrometry technique developed at Washington University, provides highly accurate and consistent results for both cognitively impaired and unimpaired individuals across all three studies.

When blood amyloid levels were combined with another major Alzheimer’s risk factor – the presence of the genetic variant APOE4 – the accuracy of the blood test was 88 percent when compared to brain imaging and 93 percent when compared to spinal tap.

“These results suggest the test can be useful in identifying nonimpaired patients who may be at risk for future dementia, offering them the opportunity to get enrolled in clinical trials when early intervention has the potential to do the most good,” Bateman said. “A negative test result also could help doctors rule out Alzheimer’s in patients whose impairments may be related to some other health issue, disease, or medication.”