1 2020 How to Buy ESR Analyzers st EDITION Your guide to gold standard Westergren erythrocyte sedimentation rate analysis 2020 Cell Counting How to Buy ESR Technology Analyzers An introduction to erythrocyte sedimentation rate and its uses The erythrocyte sedimentation rate (ESR) is a simple and inexpensive clinical laboratory test that detects increases in protein in the blood and is used as a non-specific marker of inflammation and infection. Despite the introduction of alternative methods for rapidly determining ESR, the traditional Westergren method is still considered the gold standard for testing. Both the International Council for Standardization in Haematology (ICSH) and the Clinical & Laboratory Standards Institute (CLSI) recommend this as the method of choice and use it as the standard for comparison for emerging techniques. In this eBook, we will provide a comprehensive overview of ESR analysis, including why ESR remains a valuable clinical tool, best practices for determining ESR Contents 1. Why use ESR? 2. How to determine ESR 3. Key considerations 4. Meet the ESR experts 5. ESR and COVID-19 management 6. Summary & acknowledgments 7. Editor’s picks using the Westergren method, and important considerations for choosing your ESR analyzer. Plus, hear from ESR experts and find out how this tool is aiding the management of COVID-19 in hospitals. 2 2020 Cell Counting How to Buy ESR Technology Analyzers 1. Why use ESR? ESR testing works by measuring the rate at which red blood cells (RBCs or erythrocytes) gradually aggregate and settle as a sediment at the bottom of a vertical sample tube, separating from the clear liquid plasma above. The separation of RBCs and blood plasma is influenced by the number of proteins that are bound to the RBCs. In inflammation, proteins such as acute reactive proteins bind to the surfaces of RBCs, changing their morphology and causing them to aggregate and form what is known as a rouleaux. This rouleaux sinks much more rapidly than RBCs in a normal blood sample. An ESR measurement is expressed as millimeters per hour (mm/hr), where the amount of clear plasma at the top of the sample tube (in mm) is measured after a set amount of time (traditionally one hour). The higher the ESR value, the more inflammation that is present in the body. ESR varies by individual and can fluctuate depending on normal considerations, such as: “ •D rug use (oral contraceptives and antibiotics can increase ESR; aspirin and steroids can decrease ESR) However, a very high ESR is associated with infection and can also be elevated in many inflammatory conditions, including anemia, autoimmune diseases, muscular and connective tissue disorders, some cancers and tumors, renal failure, and organ transplant rejection. Some conditions also lower the ESR, such as heart failure and some liver and kidney diseases. The test is used to indirectly detect both acute and chronic inflammation, whether to initiate a diagnosis, monitor disease activity or discern the response to treatments. However, whilst ESR detects inflammation, this test alone does not provide information on where the inflammation is in the body, nor what is causing it. As a result, ESR is often the first point of call for determining whether there is a problem and is used in conjunction with other tests. These could include cultures to investigate bacterial infection; antinuclear antibody (ANA) and rheumatoid factor (RF) tests for suspected autoimmune diseases such as rheumatoid arthritis; or serum electrophoresis to investigate cancers such as multiple myeloma and lymphoma. The higher the ESR value, the more inflammation that is present • Weight (elevated in obesity) •G ender (elevated for females, also during pregnancy and menstruation) “ • Age (moderately elevated in old age) 3 2020 How to Buy ESR Analyzers 2. How to determine ESR The gold standard technique for ESR determination is the Westergren method. Despite the introduction of new alternative techniques that promise faster and more economical results, systems based on Westergren remain the method of choice among clinicians around the world. In a typical ESR workflow for manual systems: •A 2ml whole blood sample is collected from a patient •T his is transferred into a standardized Westergren tube with a 200mm calibrated scale •T he sample is accessioned, and the tube barcode is scanned •T he sample is thoroughly mixed with anticoagulant and diluted to 4:1 • The tube is placed in a vertical rack •A fter one hour, the distance between the surface of the clear plasma and the top of the RBC sediment is measured in millimeters a. Whole blood sample b. Normal ESR after 60 minutes c. Example of an elevated ESR after 60 minutes There are several factors that must be considered that could otherwise impact the quality of results and potentially lead to false reporting. For optimal performance, a number of factors should be taken into consideration when performing ESR measurements and choosing the right ESR analyzer for your lab. Normal ESR values •0 -22 mm/hr for men •0 -29 mm/hr for women •C RP < 3 mg/L •P V 1.50-1.72 mPA 4 2020 How to Buy ESR Analyzers 3. Key considerations “ value that can be measured is much lower. The material and composition of the tubes must also be considered. Plastic tubes improve safety in the lab by promising no exposure to glass sharps and potential pathogens in case of breakage. However, there is the additional consideration of the plastics’ adhesive properties and contained plasticizers, which risk affecting the sample. Glass tubes address the risk of contamination and provide the additional benefit of reusability, promoting more sustainable practices. “ Sample quality Quality control is an essential consideration for any hematological test to ensure confidence in the accuracy and precision of results. To retain quality in blood samples, ESR tests should be performed within four hours of sample collection. This reduces the risk of associated crenation and sphering of stagnated RBCs, which would otherwise interfere with normal sedimentation rates. The use of vacuum tubes allows for closed-tube testing Tube type Uniformity of tubes is essential in ensuring reliability in results. Tube length and diameter must be kept constant throughout the lab. It is recommended that tubes are at least 200mm and 2.55mm in diameter for manual testing, but many automated analyzers use tubes that are 8x120mm. Shorter tubes will decrease the ESR as the maximum abnormal Orientation The orientation of the ESR tube can also influence ESR, as tilting the tube causes RBCs to aggregate along the lower side while plasma rises along the upper side, causing the appearance of a falsely raised or reduced ESR. 5 2020 How to Buy ESR Analyzers Safety Collecting hematological samples from patients incurs the risk of exposure to bloodborne pathogens. However, the use of vacuum tubes allows for closed-tube testing. This provides direct sample collection and eliminates the need for sample transfer, saving time and reducing the risk of exposure to patient blood samples. The use of vacuum tubes also requires less blood to be drawn (1ml) and reduces the risk of air bubbles in the sample, which can lead to a falsely increased ESR. Vacuum ESR tubes, such as those from ELITechGroup, allow for closed-tube testing and can come prefilled with sodium citrate for automatic sample dilution. Anticoagulant and dilution Anticoagulants, such as sodium citrate or ethylenediaminetetraacetic acid (EDTA), are added to blood samples prior to ESR measurement to prevent coagulation and preserve normal RBC morphology. The Westergren method requires a 4:1 ratio of blood to anticoagulant. An excess of anticoagulant will decrease the natural ESR, and too little anticoagulant will cause your blood sample to clot and increase the ESR. Vacuum ESR tubes can come prefilled with an anticoagulant, which allows for automatic and controlled dilution of samples. Liquid-based anticoagulants, such as sodium citrate, can cause errors in dilution of the blood sample if measured inaccurately, consequently affecting the ESR rate. This has led many clinicians to modify the Westergren method and use solid-based EDTA instead. Temperature If uncontrolled, temperature will impact the ESR. Increases in the temperature of the sample will cause an increase in the ESR. As a result, testing temperatures should be kept constant, between 18°C and 25°C, and any refrigerated samples should not be tested until they have reached a standardized room temperature once again. Run time By default, ESR testing by the Westergren method takes 60 minutes. However, with the introduction of automated instrumentation, some analyzers allow for the extrapolation of data from a 30-minute or even 15-minute test. This allows for more rapid testing, along with the assurance of accuracy and reliability. Analyzer capacity When choosing an ESR analyzer, an important consideration is the expected frequency of ESR testing and throughput required. This will determine the number of tube positions required in your analyzer. Automation Many of the above considerations can be accounted for using automation. Many automated ESR analyzers incorporate the traditional gold standard Westergren method, whilst making analysis safer and more accurate than manual methods. Automation can be used to control for variables, such as temperature and tube tilting, that may otherwise influence the results from manual analysis. Automation also allows for the integration of features that help streamline a clinical laboratory and optimize its workflows, including: arcode scanning allows clinicians to keep B track of blood samples and patient results more easily. Integrated quality control capabilities ensure accuracy and reliability in results, whilst reducing analyzer downtime. On-board mixers ensure samples are well mixed, providing standardization not easily achieved through manual methods, as well as removing the need for additional mixing equipment. Alternative methods The Wintrobe method is very similar to the Westergren method, but the tubes used are much shorter (100mm) and thinner. As a 6 2020 How to Buy ESR Analyzers result, this method is less sensitive and is now often used for demonstration purposes only. Newer methods of analysis, such as Test-1 and iSED analyzers, promise faster results (20-second readouts) from much lower volumes of blood. However, it takes approximately ten minutes for RBCs to fall at a steady rate, therefore tests that claim to provide results before this physical process is complete could lead to false negatives and increase the risk of missed diagnosis. There are also other tests that are used as an initial indication of inflammation, such as C-reactive protein (acute phase protein or CRP) and plasma viscosity (PV). Of these tests, CRP changes most rapidly in response to inflammation and PV can be more sensitive and specific for certain disorders such as rheumatoid arthritis. However, the attraction of ESR for busy clinical environments such as hospitals is the ease of use and lack of complex laboratory equipment required. ESR also takes many different proteins into account, making it the method of choice for doctors wanting an initial, broad test for inflammation. 7 2020 How to Buy ESR Analyzers 4. Meet the ESR experts Kathy Kalinowski founded ProSource Lab Consulting, LLC in 2014 and has since been providing a variety of consulting services to a diverse mix of physician practices for their in-office laboratories. What are the common challenges or pitfalls of ESR analysis? The ESR test is a good example of how rapidly new test methods have been introduced to achieve safer and more efficient testing and it deserves a good quality review. Many of the challenges with ESR analysis are method dependent and have been resolved with many modified Westergren methods. Since there are many new technologies and instruments that are addressing the concerns of ESR testing, it is vitally important to address the harmonization of ESR testing. re-analytic testing phase: Proper specimen P collection and mixing is required to prevent hemolysis and to avoid coagulation. Specific package insert guidelines should be reviewed and followed for proper collection and storage. Generally, ESR testing should be performed within four hours if left at room temperature, but specimens may be refrigerated for up to 12 hours if brought to room temperature and mixed well prior to testing. Due to this short stability window, referred specimens often have a high sample rejection rate. Analytic testing phase: •Q uality control must be performed following the package insert guidelines and in accordance with state and federal regulatory agencies. Proper mixing of the tube is essential, and the tube or vial will have a minimum fill line to ensure an accurate read. Manual methods also require the ESR rack to be placed on a level surface, free from vibration. •O ne very serious consideration when selecting methods is the exposure risk to the testing personnel. Manually filling tubes with whole blood (and manipulation 8 2020 How to Buy ESR Analyzers of pipettes with manual methods) requires personal protective equipment (PPE) and adequate barriers. Positive sample identification can also be particularly challenging with manual analysis as the pipette needs to be free of labels for a proper read. •T he timing of manual tests needs to be exact; if this read is missed, a new test needs to be set up, thereby increasing the turnaround time and risking the possibility of insufficient whole blood for repeat testing. This one-hour method places practical limitations on laboratory workflow. ost-analytic testing phase: Alternate P methods, such as erythrocyte aggregation, and Westergren methods are not interchangeable and the chosen method should be identified on the patient report. “It is vitally important to address the harmonization of ESR testing” What should one look for in an ESR analyzer? Most important are features that provide maximum employee and patient safety, and accurate and reliable testing, such as closed-tube systems, positive sample identification, onboard mixing, random access testing, interface capability, and adequate throughput to meet the lab needs. I would recommend the Excyte automated ESR analyzer as this line contains scalable products with many of the key features mentioned above. Most importantly, the Excyte can be operated using the closed-tube system with random access capabilities. Other features such as interfacing, barcode scanning, results printing, and a 30-minute read time ensure positive patient identification and efficient operations. Todd Proud is a medical technologist with American Society for Clinical Pathology (ASCP) certification and is currently the technical support manager at ELITechGroup. What are the common challenges or pitfalls of ESR analysis? It is my opinion that all methods should be compared to the gold standard Westergren method. Over time, ESR analysis has drifted away from this method and it has caused a lot of confusion concerning accurate testing. Therefore, providing education, of all the different methods of ESR analysis, is of great importance. The collection and timely delivery of the sample can also sometimes be challenging and the preparation of the sample for testing can be more difficult with some methods and create biohazard challenges. “Providing education is of great importance” What are the benefits of a tried and tested method? The Westergren method was developed in 1921 and is still considered the gold standard for ESR testing. This is because it has provided a consistent method that has been used for almost 100 years and still gives the most accurate and consistent results. What should one look for in an analyzer? The first thing you should be looking for is how the analyzer compares in terms of methodology and result correlation to the gold standard Westergren method. You also need to look at ease of sample collection, ease of sample analysis, and the dependability and technical support, which is essential to ensure your analyzer is always operational. Finally, the reputation of the system you are purchasing is important and the Excyte range is designed to surpass every one of the above points. 9 2020 How to Buy ESR Analyzers What ESR solutions does ELITechGroup offer? The Excyte portfolio offers all you need to ensure quality in your ESR analysis, including a wide range of analyzers to meet the needs of any sized lab, such as the Excyte Mini, Excyte 20, and Excyte 40. There is also an Excyte line of direct-draw blood collection tubes, available in glass or unbreakable plastic, or you can use tubes that you pour the appropriate blood into before analysis. ELITechGroup also has the ACCU-SED quality control material and a peer group quality assurance program called VQC to help assure the most accurate results. Top tips from the experts: • Choose a method that closely follows and correlates to the Westergren ESR method • Automate to improve safety and efficiency in sample collection, preparation, and analysis • Use a closed-tube system to minimize exposure and eliminate a possible sharps incident • Train your testing personnel thoroughly and perform competency assessment as required • Utilize a proven quality control and quality assurance program 10 2020 How to Buy ESR Analyzers 5. ESR and COVID-19 management Though ESR lacks diagnostic specificity, this measurement could be a particularly valuable tool for the management of patients affected by COVID-19. Measured ESRs increase with the severity of inflammation present in the body and recent studies have also shown that more severe COVID-19 cases show more prominent “Common laboratory findings among hospitalized patients with COVID-19 include elevated inflammatory markers such as Ferritin, CRP, and ESR. Many studies focus on the relevance of CRP levels in these patients, but there have been some cases of significant ESR findings that make this a relevant test in the management of COVID-19 cases.” Kathy Kalinowski, ProSource Lab Consulting elevations in ESR. This reflects the heightened inflammatory response and subsequent expression of acute-phase proteins. Therefore, ESR could help clinics rapidly distinguish between severe and non-severe COVID-19 cases, ensuring early diagnosis, effective screening, and improved prioritization of care. “This is still a new and uncharted subject. We are just finding out that monitoring inflammation in Covid-19 patients can be helpful in determining a patient’s progress or lack of progress. ESR is the most widely used method for monitoring inflammation so it is logical that it may be a useful method to assist physicians with the treatment of these patients.” Todd Proud, ELITechGroup 11 2020 How to Buy ESR Analyzers 6. Summary & acknowledgments We hope that this eBook has provided you with some key considerations when choosing an ESR analyzer and complementary technology. Many different types of ESR instrumentation and analysis methodologies exist in the market and selecting the right equipment for your lab’s needs may seem like an overwhelming task. However, SelectScience has a comprehensive range of resources, videos, and exclusive interviews that capture expert opinions and showcase the latest developments in technologies like this to help simplify your choice. Plus, you can read reviews written by fellow scientists and healthcare professionals, adding a valuable dimension to your purchasing decision. We’d love to hear from you, so please feel free to share your experience and successes by leaving a 2-minute review. Acknowledgements This eBook was produced with help and guidance from the following individuals: •D ianna Poissant, Senior Director of Global Sales and Business Development, ESR, ELITechGroup •K athy Kalinowski, Founder and President, ProSource Lab Consulting, LLC • Todd Proud, Director, Technical Support, ELITechGroup 12 2020 How to Buy ESR Analyzers 7. Editor’s Picks Excyte® 20 Automated ESR Analyzer by ELITechGroup Excyte® Mini Automated ESR Analyzer by ELITechGroup “This is a great sedimentation rate analyzer and is very reliable and accurate. This analyzer is very easy to use: it positively identifies each specimen, mixes it and sends results across to our LIS, all with minimal user effort.” Spencer Waitman, Medical Park Family Care Inc “Best decision ever! This is a great product! We were using the Westergren method and making the switch to this automated method was probably the best thing our lab did. This instrument is user friendly, quick, easy, and reliable. Highly recommend this product.” Michael Iodice, Beth Israel Deaconess Hospital-Milton ESR-Chex Plus by Streck Inc. EZ-Rate™ ESR Pipette by Globe Scientific Inc. “Definitely would recommend this product. It is a great product for the clinical laboratory.” Terri Tucker, Frances Mahon Deaconess Hospital “The EZ-Rate allows an easy procedure for the ESR. It is a good selection for ESR manual method. Globe Scientific is a good company for laboratory consumables.” Carlos Alfredo Torres, Labcare de Colombia ltda 13