Substantial strides have been made in the diagnosis, treatment, and prevention of blood diseases. The new technologies to be used in combination with cytostatic therapy have been developed, based on increased understanding of the biology of neoplasia. The diagnosis of several diseases is based exclusively on cytogenetic and molecular analysis which has become a part of routine diagnostic management. Moreover, molecular definition has allowed the introduction of therapy targeted at molecular change characteristic for a given disease. The introduction of novel agents for the treatment of hematological disorders has resulted in great improvement in response rate and median survival.

The modern hematology instruments represent a great advance in technical capabilities, providing high-throughput and high-resolution measurements of a single RBC and characteristics for tens of thousands of cells. These next-gen instruments provide high-resolution and high-throughput characterization not just of RBC populations but also of white blood cell lineages and platelets. The characterization of white blood cell lineages and subtypes has become particularly sophisticated in recent years. Models of the population dynamics of these other cell types will likely show important details of physiology, with even greater diagnostic possibilities.

Indian Market

hematology-pie

The Indian hematology instruments and reagents market in 2015 increased by 17 percent in value terms, and there was an increase of 13 percent for instruments in quantity terms. Reagents continued to hold sway with a 62 percent share in the total market.

While all the segments are increasing, the 3-part instruments are gradually being replaced by 5-part entry level instruments. Each and every brand is strengthening its entry level 5-part analyzers product range, because that is where the increase in demand is emanating from. Semi automated instruments, which were expected to make a complete exit, continue to have presence. In 2015, intense competition has resulted in stable prices.

The private sector continues to dominate this segment. Medall Healthcare Pvt Limited, operating 60 centers across South India, procured 200 instruments in 2015. This year, government buying was slow. Large corporate chains are either replacing their instruments or having made their procurements are more or less at a saturated demand level.

Global Market Dynamics

The global hematology instruments market is expected to exceed USD 2.6 billion by 2020, growing at a CAGR of 5 percent. {mosimage}

The global large-capital equipment hematology instruments market is likely to reach USD 1.3 billion by 2020, growing at a CAGR of over 4.5 percent.

hematology-table

The global bench-top hematology instruments market is projected to exceed USD 1 billion by 2020, growing at a CAGR of around 5 percent.

The global point-of-care (POC) hematology instruments market is likely to exceed USD 349 million by 2020, growing at a CAGR of over 6 percent.

Rising incidences of blood-related disorders, technological advancements, government initiatives supporting healthcare infrastructure are some of the factors fueling the growth of the hematology instruments and reagents market. Integration of flow-cytometry techniques in analyzers, developments in POC hematology testing and introduction of digital imaging systems in labs and increasing use of microfluidics technology in analyzers are creating opportunities in the global hematology diagnostics market whereas product recalls, high cost of hematology diagnostic instruments, lesser adoption in emerging economies and poor health insurance and reimbursement coverage are the major restraints of the global hematology market.

There is a significant market shift of hematology diagnostics instruments from manual testing to semi-automated or fully automated instruments. The manufacturers compete mainly on the number of parameters measured, reagents consumed, style, and price.

Technological Trends

hematology-pie hematology-pie

Automation in laboratories. The era of computerization has not bypassed hematology instrumentation. The newest cell counters are linked to microcomputers for sample monitoring and data manipulation. Electronic, reproducibility, and carryover data are calculated and flagged on the computer terminal, if out of range. Results of control samples are directly stored in computer files. Through advances in electronic, photo-optical, and fluidic technology, new instruments have achieved high resolution and wide dynamic range in cell sizing. While previous cell counters reported seven parameters, the latest instruments can measure or compute up to 18 parameters. A key improvement enabling these instruments to accurately count platelets in the presence of red cells is hydrodynamic focusing, whereby particle-free sheath fluid centers the cells in the aperture and prevents recirculation. In research laboratories, laser light scattering measurements of cells in flowing fluid are used to provide new information about their biophysical and biochemical properties. In automated ektacytometry, laser diffraction patterns of red cells under fluid shear stress enable rapid measurements of red cell deformability in various media. Pathologic red cells may be identified by lesion such as altered surface-to-volume ratio, abnormal cell-membrane composition, or abnormal intracellular hemoglobin rather than by shape.

Point-of-care testing (POCT) in hematology. There is a growing interest in new or rediscovered laboratory technologies that can be utilized without the presence of specialized personnel, at the bedside and/or in extreme field conditions, with limited or no infrastructure and without specialized maintenance services. POCT hematology instruments are affordable, sensitive, specific, user-friendly, rapid, and robust. POCT devices that are increasingly utilized include dry-chemistry analyzers, rapid immunological tests, coagulometers and hematology analyzers. In the hospital setting, blood transfusion is an essential treatment that is available worldwide; however, the more current, sophisticated, and high-throughput technologies utilized in transfusion medicine in high-income countries are hardly suitable for blood banks in resource-constrained health services. In these contexts, few blood units are collected and transfused daily and often only in emergencies; therefore, instruments and devices that allow single or small-batch testing and rapid turnaround time are required. Improvement in transfusion safety depends on technologies that can be safely operated in disadvantaged situations.

hematology-table

Dry hematology POC instruments provide a self-contained testing solution that is perfect for prescribed POC CBC testing. Rather than sending samples away to the laboratory for analysis, one can get quantitative CBC results in just a few minutes. This promotes improved patient outcomes by allowing to make real-time treatment decisions and intervene earlier. These dry hematology instruments do not require any routine preventative maintenance and there is no need to periodically calibrate the device. The results do not drift over time due to changes in flow characteristics of filters or other components. These POCT systems have multiple built-in analytical quality control checks that maintain the overall system integrity and the quality of test results. These instruments perform numerous checks, such as centrifuge RPM, image quality, and proper cell layer formation on each and every sample to provide accurate CBC testing results.

Flow cytometry finding way to hematology laboratories. The advent of flow cytometry in hematology laboratories has led to substantial impact on the monitoring and diagnosis of diseases. It helps measuring optical and fluorescence characteristics of individual cells as they flow in single file through a stream of liquid. In hematology, immunophenotyping is used to study proteins expressed by cells, so that they can be accurately identified. Immunophenotyping by flow cytometry is used for the diagnosis of new leukemias, it allows certain acute myeloid leukemias to be distinguished from one another, and it can also be used to detect minimal residual disease. Flow cytometry can be used to identify platelet abnormalities such as autoimmune thrombocytopenia purpura and those associated with conditions such as Bernard-Soulier disease. Flow cytometry can also aid diagnosis of red cell disorders such as hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria.

Advent of microfluidics. The microfluidic device utilizes electronics to count the different types of blood cells based on their size and the properties of their membranes. In order to count white blood cells and their differentials, red blood cells are selectively lysed and the remaining white blood cells counted. Assessment of platelet function and coagulation under flow conditions can augment traditional static assays used to evaluate patients with suspected hemostatic or thrombotic disorders. Among the available flow-based assays, microfluidic devices require the smallest blood volume and provide multiple output options. These assays are based on the presence of wall shear stress that mimics in vivo interactions between blood components and vessel walls. Microfluidic devices can generate essential information regarding homeostatic regulation of platelet activation and subsequent engagement of the coagulation cascade leading to fibrin deposition and clot formation. Microfluidic assays may also reveal consistent patterns of hemostatic or thrombotic pathology, and could aid in assessing and monitoring patient-specific effects of coagulation-modifying therapies.

Challenges and Opportunities

hematology-pie hematology-pie

Automation of leukocyte differentials has been achieved by two different methods. Computerized electro-optical microscopes analyze 100 to 500 white cells on Wright-stained smears and classify cells by recognizing patterns of nuclear size, shape, and chromatin structure, and cytoplasmic color and granulation. Automated flow cytochemistry can rapidly classify much larger numbers (10,000) of white cells by joint measurement of cytochemical stain intensity (absorbance) and cell size (optical scatter); however, neutrophils cannot be sub-classified by this technique. In the future, the combination of multiple fluorescent probes and light-scattering measurements at different angles may result in rapid and complete cytofluorographic leukocyte differentials. The future of hematology will focus on new technologic developments currently in use in clinical laboratories.

POCT remains a major interest among laboratorians, and a significant growth area for in vitro diagnostics manufacturers. But access to the convenience and speed of POCT is not a solution for all diagnostic needs. POCTs are sometimes not used according to their instructions, and experts caution that proper use is essential for attaining correct test results. Many clinical labs are involved in the development of new and emerging technologies for hematology lab applications. In some cases, such efforts are focused on laboratory-developed procedures to be performed within the lab's own facilities.

But labs are also engaged with in vitro diagnostics manufacturers to examine and refine future generations of instruments and related tests, giving them advanced insight into such products long before they are ready for commercialization. Image-analysis technologies have the potential to supplant much of the manual slide review that occurs in hematology laboratories. The main challenges include obtaining a monolayer of cells and the appropriate classification of abnormal cells.

The ongoing revolution of diagnostic testing, squeezed between reduced funding and increasing volumes, carries notable implications in the way laboratory resources are organized and coagulation tests delivered. It is, therefore, predictable that the newer generation of hemostasis analyzers may be designed to face these emerging needs whilst maintaining a high degree in the quality of testing. The future of the hemostasis is currently unpredictable. The challenge of coagulation analysis in the context of the widespread use of novel anticoagulants, which is very likely increasing further in the future, is a paradigmatic example. According to ongoing reorganization of laboratory diagnostics, continuous technological innovations such as miniaturization, improvement of hardware and software components, and predictable trends of disease prevalence, some basic ideas can be proposed to envisage a next-generation coagulation analyzer.

Priyank Dubey, Product Manager - Hematology, Alere Medical Pvt. Ltd.
Industry Speak
An Increasingly Competitive Market

Hematology domain is growing at a tremendous rate. In 2015, the market grew over 15 percent compared to 2014, and the same rate of growth is expected to continue in 2016. The factors which are fueling this growth are increase in overall healthcare expenditure; rising healthcare spend from Indian government, decreasing mortality rate, increasing aging population, and lifestyle related diseases. This growth has also percolated down to Tier-II and Tier-III cities, and they too have started to move toward better medical and testing facilities. This is evident from growing number of standalone hospitals and laboratories in smaller cities and towns. Recently, corporate hospital chains and labs chains have also begun to step out of metros and A-towns to capitalize on this opportunity.{mosimage}

The market has become increasingly competitive, and vitality in this scenario can only be ensured with clear understanding of the segment and the ability to provide product and services that fit. This has led to a breed of products that are faster, have better technology, offer advanced parameters, are modular and take up minimum bench space, and importantly ensure excellent return on investment and affordability.

In the 3-part segment, factors such as customer references, certifications, throughput, support reputation, and overall brand presence are beginning to take precedence in purchase decisions. So the product should be fast, with better technology, offer seamless interface, should be compact and easily serviceable, and yet produce excellent results utilizing minimum reagents. The next thing in this segment will be systems that are still smaller and suitable for near-patient analyses, are portable, affordable and yet provide quality results. Increasing penetration of 5-part systems in smaller cities and towns is leading to stellar growth in this segment. The market for high-end systems has been driven by differentiation in detection technology, reporting of abnormal parameters, throughput, and modularity. The entry-level systems are the main drivers of this aggressive growth. These systems are compact, with touch screen operations, ergonomically designed, have very efficient reagent usage, and produce good-quality results. And thus these systems become the natural choice for 3-part customers looking to provide quality 5-part results, and for newer setups working to create differentiation in the market.

Alere's product line has been specifically designed to fulfill the requirements across segments, and paving the way for affordable and high-quality hematology testing.

Priyank Dubey
Product Manager - Hematology,
Alere Medical Pvt. Ltd.

Dr R Selvakumar, Adviser, CPC Diagnostics
Industry Speak
An Insight into Immunoturbidimetry

In a biochemistry laboratory there are hundreds of proteins, peptides, steroids, and tumor markers that cannot be quantitated by conventional methods, because these molecules are present in the body fluids in very small quantities. Immunochemical methods have replaced the chromatographic techniques in clinical diagnostics, offering fast detection of antibodies associated with specific diseases, disease biomarkers, hormones, and pharmaceuticals. Immunochemistry offers simple, rapid, robust yet sensitive and, in most cases, easily automated methods which could be easily adopted in routine clinical laboratories. {mosimage}

All immunochemical methods are based on a highly specific reaction between an antigen and an antibody. Assay specificity and sensitivity are determined by the quality of antibodies used in the method. Nowadays, monoclonal antibodies are used in many of the immunoassays.

Nephelometry and immunoturbidimetry are techniques that are adopted by many laboratories for the estimation of several parameters like high-sensitive CRP, CRP, micro albumin, ferritin, ceruloplasmin, glycated hemoglobulins, antithrombin III, fibrinogen, Rh factor, and myoglobin. The nephlometric technique uses the fact that antigen-antibody complexes in a solution scatter light at various angles to the direction of the incident light. A nephelometer uses a high-intensity light source that passes through a reaction vessel containing the immunoreactants, and a photo detector collects the light-scattering signal. The reaction requires at least a bivalent immunoglobulin and an antigen with at least two epitopes.

Immunoturbidimetric assays can also be used for quantitative measurement of certain drugs or biomarkers in body fluids like serum, plasma, or urine. The assays are based on an agglutination reaction induced by the antigen-antibody binding. When a light at a particular wave length is directed to the sample mixture, the absorbance change is measured photometrically, which is directly proportional to the concentration of the antigen. A concentration-dependent classic agglutination curve could be constructed and used.

CPC Diagnostics is launching a table-top analyzer, Turbospec, manufactured by Awareness Technologies Inc., USA, which is convenient to use in the laboratories for immunoturbidimetry. This can handle both antigen-antibody turbidimetry as well as latex-enhanced turbidimetry. The analyzer can perform onboard dilution of samples and calibrators, and has a cooling system for the reagents. The complementary reagents have good linearity, very high dose-hook effect, and good low-end sensitivity and specificity. The analyzer can perform multipoint calibration, with serial dilution of a single calibrator, and is capable of plotting any kind of curves. With all these features, the measurement of various parameters becomes as good as nephelometry.

Dr R Selvakumar
Adviser,
CPC Diagnostics

Santosh Aghamkar, Director-Central Asia and India, Medica Corporation
Industry Speak
Technologist's Assistant in Busy Laboratories

In a typical lab, there are many challenges faced when it comes to slide preparation and microscopy, which even today is done manually. The manual methods employ microscopy and depend on the lab technologist's judgment to locate and classify cells.{mosimage}

Skilled hematology technologists are difficult to be seen and are hard to find. As a result, in most of the cases, it is the generalized technologists who do the multitasking of reporting a chemistry result, a PT/APTT result, and even classifying the differential - all in one instance. Standard cell classification is hard to administer and evaluate in laboratories using manual cell differential methodology. Therefore, there may be difference in the way cells are interpreted from technician to technician and from shift to shift.

Automating the manual differential process makes considerable improvements in productivity for laboratories that need to do more with less. A new technology - automated cell image analysis - promises to help surmount most of the concerns. The automation of time-consuming manual white-cell differentials offers attractive operating, financial, and patient care benefits.

Automated cell image analysis. Many of the problems and concerns can be addressed by employing new advanced cell-image-analysis systems as laboratory assistants. These analyzers support hematology technologists by automating and simplifying substantial parts of the manual white blood-cell-differential process. The technology incorporates advanced imaging and pattern recognition software to automatically locate white cells on a blood smear, digitally store the images, pre-classify them, and then present them for review by the technologist, grouped by cell type on an LCD display.

Cells not falling in any normal category are placed in the other category. The technologists then can review the abnormal cells and re-classify them. All of the results are stored in digital form and are easily accessible for visual review. In short, the technologists need not find the cells on the slide as they did in the manual differential process - the analyzer does it for them. Now, the technologists only need to quickly review the cell pre-classification, which better utilizes their skills and expertise.

Automated cell-image-analysis systems provide substantial benefits for today's multitasking labs at a very affordable price.

Santosh Aghamkar
Director-Central Asia and India,
Medica Corporation

Dr Rajeev Gautam, President, HORIBA India Pvt. Ltd.
Industry Speak
Quality and Affordability Is Today's Need

Diagnostics is an important component of improved value chain in healthcare sector by enabling accurate detection of health risks and diseases at earlier stages, thus improving treatment and disease management while diminishing subsequent health problems and their associated costs. With improving economic indicators for India, healthcare spend has increased.

As a result of its growing research and development program, HORIBA Medical has recently developed a new product that aims to better meet the needs of today's clinical laboratories. In recent years, healthcare diagnostics manufacturers have had to adapt to changing needs. While affordability remains a key requirement for all, more advanced countries frequently seek this through increased automation and high-performance medical diagnostics, whereas emerging countries ask for diagnostic solutions to raise their quality standards.

The new Yumizen family is designed to meet all these challenging worldwide requirements. With the company's proven technologies and innovation, the Yumizen H500 is a compact and robust hematology analyzer tailored for all types of laboratories and other clinical settings demanding easy operation and reliable analysis, such as routine and satellite laboratories, emergency care, and physicians' offices.

The HORIBA Medical segment designs, develops, and distributes worldwide in IVD systems mainly destined for biological analysis in medical laboratories. These automated analyzers meet the needs of various users including patients, doctors, private laboratories, clinics, and university hospitals. HORIBA's expertise in IVD is one of the most respected in hematology worldwide and contributes today to the health of tomorrow.

Dr Rajeev Gautam
President,
HORIBA India Pvt. Ltd.

Archana Ravindranath, Sr. Business Manager-Hematology, Transasia Bio-Medicals Ltd.
Industry Speak
Unprecedented Opportunities Waiting Ahead

Hematologists today are endowed with unprecedented opportunities for usage of cutting-edge technologies for enumeration of advanced clinical parameters, thereby enhancing improvement in detection of cellular abnormalities and providing effective solutions to clinicians for better patient care.

On market trend

Enhanced awareness amongst clinicians for these parameters has been observed in the recent years. IPF (immature platelet fraction), Ret He (hemoglobin equivalent in reticulocytes) have become the sought-after parameters in today's world. Lots of investments are being made in research and development and for advancement of better technologies to improve insights for treating blood disorders. Research is ongoing for manufacturing hematology analyzers with improved sensitivity and specificity to capture abnormalities and minimize smear reviews. There is also growth in the number of corporate hospitals in Tier-II and Tier-III cities and a proliferation of satellite centers by chain labs in remote areas. Rising technological advances, adoption of basic flow cytometry technologies in modern hematology analyzers, increased demand for high-throughput hematology analyzers, development of highly sensitive POC hematology testing, and medical tourism have fuelled growth. Laboratories are now focusing on accreditations and adoption of automation.

On technology trends

There is a growing trend for automation with user-friendly interface. Analyzers are integrated with automated slide-maker stainers, tube sorters, barcode terminals, and LIS and HIS for streamlining work processes. Such advancements have led to improved TAT and elimination of errors in clinical reporting. Nowadays, analyzers are equipped with real-time quality-assurance, preventive maintenance programs to boost uptime, middleware systems, and automated digital imaging. Automated capture of digital images in abnormal findings can streamline laboratory work flow as these can be viewed thus minimizing manual microscopy smear review to a great extent. Remote review and sharing of the digital images to multiple viewing workstations and mobile devices is possible, thereby enhancing standardization of morphological reviews.

Challenges and opportunities

Space is a major constraint and hence labs choose ergonomically designed analyzers with small footprints. There is an increased demand for automation even in smaller workload standalone labs and rentals with low cost per test. Budgetary constraints, lack of skilled and experienced technologists, intense competition among players, high cost of diagnostics, and less proliferated health insurance coverage are few of the challenges. Abundant opportunities are in POC testing which is still an emerging segment. Rural India is waiting to get tapped with technological advances in diagnosis.

Archana Ravindranath
Sr. Business Manager-Hematology,
Transasia Bio-Medicals Ltd.

Nikhil Panjwani, Assistant Marketing Manager-IVD, Mindray Medical India Pvt. Ltd.
Industry Speak
Emerging Advancement and Trends

Hematology laboratory is increasingly becoming the backbone of diagnosis of all diseases and prognosis of patients. Hematology laboratory has been transforming fast and the trends are changing. Laboratory workload was expected to consolidate in the last few years in terms of sample volume, and big labs were expected to go for high-end instruments in a big way. However, the consolidation did not happen and scattering of workload is still prevalent. This has contributed to sustained growth in the high-end 3-PDA segment and the low-end 5-PDA segment. 5-PDA CBC differentials are finding their niche by providing clinicians extensive disease niceties. Hematology analyzers boast features that were developed by following the established rule of demand modulating the supply to meet and even exceed the requirements of the laboratories. Increasing adoption of automated hematology instruments, rising technological advancements, and integration of basic flow-cytometry techniques in modern hematology analyzers are some of the key factors driving the growth of the hematology analyzers and reagents market. Market growth is also fueled by increasing government programs, which support healthcare infrastructure. Nevertheless, hematology diagnostic devices market is expected to increase with growing support from private and administration associations.{mosimage}

Hematology instruments make high-value-added medical testing possible by detecting abnormal cells in addition to measuring the five types of white blood cells. Sophisticated systems are in continuous demand where one can put the samples in process and continue with other work. It is evident that clinical practitioners are well informed on the new parameters and they are using it in day-to-day practice. This has created demand for new parameters like optical platelet, IPF, RHE, MRV, and IMG. Addressing these needs, Mindray has gone ahead and provided its users with new parameters that enhance the productivity of high-end laboratories.

Nikhil Panjwani
Assistant Marketing Manager-IVD,
Mindray Medical India Pvt. Ltd.

Rajesh M Patel, Head-Business Operations, Meril Diagnostics Pvt. Ltd.
Industry Speak
Reagents-Changing Trends

Open-system analyzers provide the laboratory with a choice to opt for reagents with at par performance of analyzer manufacturer's reagents though at a much economical price. Such has been the scenario in biochemistry, immunology, and coagulation analyzers from the advent of Indian diagnostic market. But unfortunately, the point of view on hematology analyzers is unique in the sense that such systems are considered closed. The end-user does not have any choice but to accept the high cost per test having chosen the hematology analyzer for its performance and brand equity. {mosimage}

Any company trying to alter this trend and provide at par performance economical hematology reagents is termed spurious and such customers are considered non-quality-conscious customers. Hematology analyzer manufacturers also ensure no service in order to compel the customer to stop using compatible hematology reagents. The market also preys on the myth that the usage of such reagents will damage the hardware of the analyzer.

There is a change in perception of the market over the last few years with the advent of international brands launching system-compatible hematology reagents. Customers have understood the benefits of using such compatible reagents without any compromise on quality. Even recommended controls are used regularly to ensure accuracy and precision. The use of system-compatible reagents is no longer a hindrance in accreditation of laboratories provided all documents are provided by the manufacturer.

Rajesh M Patel
Head-Business Operations,
Meril Diagnostics Pvt. Ltd.


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