Sysmex Connect - October 2021 - Staff

October 2021

Sysmex Connect

In this issue Sysmex UK Virtual Symposium 2021 New Quality Control and Calibration Webinars Microbiology Training Week New Added Value Webinars New PMI Booking System

www.sysmex.co.uk

Sysmex Connect – October 2021

In this issue

Note from the Editor Welcome back to Sysmex Connect!

03 Sysmex Academy updates

Sysmex Connect shares updates from Sysmex UK and the latest news and innovations from the world of Pathology.

04 Sysmex Quality Concept Webinar Series

The new Sysmex Academy app is coming soon! Turn to page 9 for more information on the release date, and the flexible benefits that this offline training app can bring whilst being on the go. We are excited to launch the Sysmex Quality Concept Webinars. A free-of-charge webinar series by the haematology product specialists. Turn to page 4 to find out more about the release dates, sequential webinar material and enrolment.

05 Microbiology Training Week 06 Big digital pathology changes at Royal Southampton NHS Trust

Microbiology Training Week was a huge success, with high numbers of participants joining the 17 live webinars and utilising the 8 self-directed learning modules, for all over the UK and Ireland. On page 6, you will find the Royal Southampton NHS Trust exploring digitalisation of their histology and hematopathology workflows, and consequently taking their first steps in adopting some big changes.

07 'Sixty Seconds on Haemostasis' interview 08 Sysmex UK Virtual Symposium 2021 09 Sysmex Added Value Webinars

Moving through the issue we are given an exclusive ‘Sixty Seconds on Haemostasis’ interview with Dr. Chris Gardiner. The Sysmex UK Virtual Symposium is approaching, save the date! Find out who some of the keynote speakers are this year, and how to submit your scientific poster. Turn to page 9, to register for the October and November Sysmex Added Value Webinars.

10 CyFlowTM Monoclonal Antibodies 11 New online PMI booking system 11 New standing order process

We share an update from our Environmental Committee on the company’s policy and reveal some interesting Q1 statistics on how we manage our waste. As always, we want to continue to improve our customer services and therefore share our new online PMI (Preventative Maintenance Inspections) booking system on page 13; providing a new alternative to phone calls. In continuation of improving customer satisfaction, we would also like to introduce the valuable benefits of the new standing order process followed by a useful Q&A.

12 FOB Gold 14 The Digital Cell 16 Growing Your Knowledge Sysmex Scientific Focus

Towards the end of the issue, we share our regular features; The Digital Cell and two scientific Haemostasis based articles, supporting Growing Your Knowledge.

Please do send us your suggested areas of improvement, recommendations and proposals for topics that might benefit inclusion. We love hearing from you and how we can make our newsletter most beneficial to you.

Sysmex Publications

For more information about any of the articles included in this newsletter or to share your thoughts with us, please contact: marketing@sysmex.co.uk.

We have compiled a list of recent publications on the connection between COVID-19 and haematology and haemostasis parameters.

The publication list will be regularly updated as more studies are released. For articles of interest click the link below.

We hope that you enjoy this issue and look forward to sharing future issues with you.

Sysmex Connect Editorial Team Remember to connect with us on LinkedIn.

Sysmex

The NEW Sysmex Academy app is coming soon!

SYSMEX ACADEMY APP

Your knowledge centre to go

CLICK TO VISIT PUBLICATION SITE

To be released in November 2021 2

Sysmex Connect – October 2021

Sysmex News The Abaxis Piccolo Xpress® is small in size yet big on accuracy, reliability and reproducibility, delivering real-time blood chemistry diagnostic information for care providers and their patients. The chemistry analyser allows healthcare practitioners to perform routine multi-chemistry panels using only 100μl of whole blood, serum or plasma, utilising a range of patented single-use reagent discs which contain up to 14 chemistry tests. As the device does not come into direct contact with the patient sample or the lyophilised reagent beads present in the rotor, it requires minimal maintenance from the end user.

With the Abaxis Piccolo Xpress® deployed in the patient setting, care providers can diagnose and treat conditions in a single visit, improving both the quality and efficiency of patient care. This shortens the time from presentation to treatment planning, and patients begin therapies faster, with greater compliance and satisfaction – which are keys to a successful clinical outcome.

For further information regarding the analyser, please contact our sales team at pointofcare@sysmex.co.uk.

ACCESS THE FULL LIST OF PANELS/ROTORS

Sysmex Academy Updates Sysmex UK are committed to continuously improving the customer experience. We are pleased to inform you that we will be implementing new updates on the Sysmex Academy website in the coming weeks. These updates are designed to improve your user experience, functionality, design and appearance of the platform.

ACCESS SYSMEX ACADEMY PORTAL

Key updates to look out for: Style change

Navigation

Improved font, visuals and menu layout for easier navigation.

Removal of navigation course topics in green, replaced by a new navigation icon.

Feedback

Have you visited our course release calendar?

VISIT THE SYSMEX ACADEMY COURSE RELEASE CALENDAR VIEW CALENDAR

Addition of new feedback icon to make it easier to contact us.

The Sysmex Academy course calendar shows our new upcoming course releases.

We hope these new features will improve your Sysmex Academy experience.

If you have any further questions, please feel free to contact: SAOenquiries@sysmex.co.uk 3

Sysmex Connect – October 2021

Sysmex Quality Concept Webinar Series Sysmex UK are excited to launch the Sysmex Quality Concept Webinar series. A free-ofcharge webinar series by the haematology Product Specialists.

Due to the huge success of the Embracing Statistics in the Modern Medical Laboratory series, Sysmex have developed the Sysmex Quality Concept series. A collection of four webinars that aim to support the laboratory in assessing the performance of their haematology instruments.

What webinars are available, and what will be covered?

Calibration

XbarM

What is XN Cal material?

The features of XbarM

Explanation of the target values and range

The classification of parameters and their importance in monitoring performance

The traceability of XN Cal

How to utilise XbarM effectively in the modern medical laboratory

The calibration procedure and factor assignment

Internal Quality Control

Carephere™ XQC

IQC material

What is Caresphere XQC and how it can be used by the lab

Assay values, and the significance of these values

The features of Caresphere™ XQC, and the data presented

How to review IQC performance

The reports available from Caresphere™ XQC and how to download them

The performance of parameters throughout a batch of IQC

Self-directed learning module available on Sysmex Academy for Caresphere™ XQC

EQA and the role it plays with IQC review

When are these webinars being hosted and how do you enrol?

You can enrol on to these webinars through our Sysmex Academy platform. Here you will find the webinars listed and available for you to register.

The table below shows current dates available, but more will be listed in the future. All webinars begin at 10am and last approximately 60 minutes.

Calibration 19th October 2021 16th November 2021 15th December 2021

XbarM 26th October 2021 18th November 2021 16th December 2021

Internal Quality Control 14th October 2021 17th November 2021 14th December 2021

Caresphere™ XQC 23rd November 2021 13th December 2021

Want to know more information?

Please send your query to the Sysmex UK Haematology team: haematology@sysmex.co.uk

ACCESS SYSMEX ACADEMY 4

product and service updates from Sysmex UK. There will be an opportunity to join a live chat session with Sysmex UK experts.

We continue to dedicate our annual award in memory of Carol Briggs. The Sysmex Poster Session can be enjoyed virtually this year.

Click on the link below to view this year's poster submissions.

Sysmex Connect – October 2021

Caresphere

The CN-Series

How can Caresphere™ Digital Solutions help you realise the true potential of your operational data?

Introducing the CN-Series - the next generation family of fully automated haemostasis analysers by Sysmex.

We have elected a panel of judges to mark them on a variety of criteria including scientific content, research and design. First and second place winners will be announced in the opening session on each day of the Virtual Symposium.

Microbiology Training Week

Haematology

Poster e-gallery

Monocytosis Workflow Optimisation - a new workflow concept that has been developed by Sysmex based on published scientific data.

Browse our e-gallery of poster submissions for this year’s Carol Briggs Award.

Judges Dr Timothy Farren, Head of Immunophenotyping (SIHMDS) & Honorary Senior Lecturer, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham Dr Paul Harrison, Scar Free Foundation Senior Lecturer, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham Dr Steve Kitchen, Clinical Scientist, Royal Hallamshire Hospital Stephen MacDonald, Principal Clinical Scientist, Cambridge University Hospitals NHS Foundation Trust

Carol Briggs Award 2020

To visit the e-gallery please click the link below View e-gallery

https://issuu.com/sysmexuk/docs/sys_poster_ submissions_v5?fr=sZjY3MjE2Mjk0Mjg 8 | Sysmex UK

T h e c u r r e n t COV I D -1 9 p a n d e m i c h a s l e d t o unp re ce d ente d disr uptions in the wor kp lace .

Laboratories have had to adapt to the ever-changing demands of testing regimes and Microbiolog y laboratories in particular have had to deal with a massive influx of COVID-19 samples whilst balancing their current workloads and dealing with staff absences as a direct result of the virus or self-isolation rules.

Virtual Symposium 2020 | 9 Live webinars were conducted by guest speakers from Germany and Spain, on topics such as “how innovative technology can support to fight Antimicrobial Resistance”, and on “Urinary albumin Strip assays as a screening test to replace quantitative technology”.

Sysmex UK recognised that during this time laboratory staff have contributed significantly to the public health crisis at the detriment of their own professional development. With this in mind, the Urinalysis team delivered a week-long dedicated training programme free-of-charge to our Microbiology customers.

The Urinalysis team also introduced for the first time a third-party quality control for the UF-5000 analysers called Eurocell-Body Fluid-U which will be available exclusively from Sysmex UK. The performance of this QC was shared as well as details on how to purchase this QC and how to process it on the UF-5000 analysers.

The training week was a huge success with participants joining the 17 live webinars and utilising the 8 self-directed learning modules from all over the UK and Ireland. It also provided laboratory staff with the opportunity to utilise the brand new Sysmex Academy which was launched in May 2021, and to really see the benefits of this new platform. Due to the structure of the virtual training week, it allowed laboratory staff to pick and choose which sessions to attend for minimum disruption to the continuation of laboratory services. The agenda included a range of topics providing an opportunity for all grades of staff to participate and be involved.

Sysmex UK also provided all participants a certificate after the completion of a short test to meet all training requirements and ensure staff have evidence for their continual professional development.

Carian Barber-Colegate and Daniel Evans from Public Health Wales also shared their experience in carrying out body fluid validation on the UF-5000 analysers and highlighted the ease of testing body fluids on the analyser and the benefits of utilising automation to test body fluid samples.

This training week really highlighted the unique benefits that Sysmex UK offers its customers.

We look for ward to seeing you at the next Sysmex UK Microbiology Training week 2022.

Customer feedback from the Sysmex Academy portal: “ In North Wales we have been making use of the Microbiology training week on Sysmex Academy. All staff so far attending the webinars have found them really helpful, so thank you to all at Sysmex for putting the week together!”

“ I really enjoyed the presentation and have now been on Caresphere™ to look at results.”

“ Very interesting webinar, well delivered and interactive.” “ I enjoyed the navigating through the course and it really helped me understand more.” “ Thank you so much - really good presentation and very informative.”

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Sysmex Connect – October 2021

Big digital pathology changes at Royal Southampton NHS Trust Many NHS hospital trusts have already been exploring digitisation of their histology and hematopathology workflows for some time. As the world emerges from the COVID-19 pandemic crisis in early 2021, however, it seems as though the tipping point for digital pathology may finally have arrived.

Whilst early adopters have long been pointing out the ways digital pathology can solve problems inherent in the traditional microscope/glass slide setup, many pathologists remained skeptical until recently, mainly due to lack of tangible evidence and overall reluctance to change. With COVID-19 affecting our lives and professions in so many ways, the global pandemic and the consequent lockdowns have now exposed the myriad vulnerabilities within the analog workflow. As the current health crisis has started to impinge on the pathology community's ability and natural inclination to help, even those previously reticent to take the leap are finally getting on board the digital train.

Digital pathology's ability to solve so many immediate COVID-19-caused issues has forced many hospital administrators and clinical directors to take notice.

The availability of innovation funding from Innovate UK has enabled UHS to fully adopt digital pathology and as part of this they acquired two Pannoramic P1000s (3DHISTECH) which are next generation, high capacity-high throughput slide scanners and ideal for the busy clinical setting.

Southampton join a rapidly expanding customer base of Sysmex UK digital pathology customers and many more will join them as they discover the multitude of benefits of digital pathology.

No longer constrained by physical slides, pathologists can now access and report their case work from wherever they are located, and by as much as their current circumstances permit. The process is straightforward – scanned slides in the laboratory are uploaded to case management software in a suitable, secure server environment and reporting pathologists can access these images via secure, controlled online access. Thus reporting clinicians of many disciplines are able to continue working and reporting in times such as those created by COVID-19, when self-isolation, shielding and working at home would otherwise prevent this.

Royal Southampton NHS Trust (UHS) took a precautionary step towards digital pathology in 2018 with the acquisition from Sysmex UK of a Pannoramic SCAN II slide scanner and Slide Manager software that enables storage and remote access to high resolution whole slide images. This low-capacity option enabled the trust to feel its way in to digital pathology with a solution that was ideal for what can be a steep learning curve. The set up enabled digital pathology to be used in training and MDT meetings as a first step towards full adoption.

Sysmex UK are the exclusive distributors of 3DHISTECH digital pathology solutions.

For further information please go to: https://www.sysmex.co.uk/n/products/life-science/digital-pathology.html Alternatively, e-mail kimber.simon@sysmex.co.uk 6

Sysmex Connect – October 2021

Sixty Seconds on Haemostasis Dr. Chris Gardiner (Senior Research fellow at the formerly Haemostasis Research Unit (HRU) at UCLH, London, UK) along with colleagues at HRU-UCLH, performed a performance evaluation of chemiluminescence enzyme immunoassays (CLEIA) on the new Sysmex CN-6500 haemostasis analyser. In July this year, Dr, Gardiner presented his findings for testing Haemostatic and Fibrinolytic Activation Markers and their potential Clinical Utility in COVID-19 Patients on the CN-6500 system.

Krishna Ram - Hi Dr. Gardiner, firstly thank you for taking the time for this 60 second interview. How are you? You’re back in the lab, working in Leeds…

Dr. Gardiner - In time, I can see these assays providing useful information in patients with severe COVID-19, sepsis and atypical DIC, to facilitate personalised medicine for these patients. These assays also have potential applications in cancer medicine. The benefit with the CN-6500 is the ability to automatically perform classical haemostasis assays alongside these CLEIA assays; TM, TAT, tPAI-C and PIC from a single citrate sample tube.

Dr. Gardiner - It’s been a busy few months, I moved from Buckinghamshire to West Yorkshire in June. I’m still settling in, but I’ve taken every opportunity to explore the Yorkshire Dales.

Yes, I started work in the specialist coagulation lab at St James’ University Hospital in July.

Krishna Ram - What makes the CN-6500 analyser stand-out against other automated CLEIA systems and traditional immunoassays?

Krishna Ram - Have you missed lab-life and do you miss working with Sysmex analysers in Haemostasis?

Dr. Gardiner - The wide analy tical measurement ranges, reproducibility for all the assays, along with the ease of use of the software and sample processing speed of the CN-6500. The time taken to analyse PT, APTT, Fib and D-dimer while simultaneously performing the four CLEIA tests on the same sample was 23 minutes and 30 seconds. This is a saving of many hours based on ELISA methodology for these four CLEIA assays.

The integration of chemiluminescence detection on to a main line haemostasis analyser has achieved excellent comparability of the CN-6500 against the predicate HISCL-5000 system, a fully automated rapid immunochemistry analyser.

Comparability of TM, TAT, PIC and tPAI-C in 230 clinical plasma samples between the CN-6500 and HISCL-5000 analysers.

Dr. Gardiner - It’s good to be back in a clinical lab at the sharp end of things. It’s the first time I have worked in a haemophilia comprehensive care centre. I’ve learned new assays, with different analysers and I’m still getting to grips with the IT system, so the last few weeks have been a steep learning curve but never dull.

Krishna Ram - Having now worked with Sysmex haemostasis analysers for many years, from the CA-Series to the CS-Series and now the CN-Series, do you think the advancement in technology and software on the CN-Series meets the current and future needs of haemostasis laboratories?

Dr. Gardiner - Yes – the CN-Series certainly delivers a very wide assay range with high throughput and in a small package.

Maintenance, data backups, QC and calibration procedures are much faster and more straightforward with the CN-Series, so there is very little downtime at the start of the day. The CN software and touch screen technology is also very user-friendly.

Krishna Ram - With your experience working with the CN-6500, what key analyser features stood out most for you?

Dr. Gardiner - The ability to perform routine testing and specialist assays simultaneously, without a significant drop in throughput.

The CN-6500 incorporates two components; Coag Function, and Immuno Function testing that work independently of one another, to maintain high workflow from the analyser overall.

Krishna Ram - In your open-access published ar ticle, “A p er formance evaluation of chemiluminescence enz yme immunoassays on the Sysmex CN-6500 haemostasis analyser” your study evaluated assays for: soluble thrombomodulin (TM), thrombin-antithrombin (TAT), tissue plasminogen activator/plasminogen activator inhibitor 1 complex (tPAIC) and plasmin α2 plasmin inhibitor complex (PIC).

Comparability of TM, TAT, PIC and tPAI-C in 230 clinical plasma samples between the CN-6500 and HISCL-5000 analysers.

Krishna Ram - Thank you for your time and sharing your experience of the CN-6500.

Do you see there being a clinical need or interest in these assays for haemostasis service providers in the NHS?

Dr. Gardiner - My pleasure, thank you.

For more information on the CN-Series, please visit: https://www.sysmex.co.uk/n/products/products-detail/cn-series-analysers.html Author: Krishna Ram, Product Marketing Manager, Haemostasis.

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Sysmex Connect – October 2021

We look forward to seeing you at this year’s

ENGAGE

NETWORKING!

Register

with presentations on a range of topics

Login

Live

OPPORTUNITY

to gain CPD recognition

Live Webinars from 10am - 1pm Networking and Expo booths 1pm - 2pm

23rd - 25th November 2021

PARTICIPATE

in live Q&A sessions with keynote speakers

We are delighted that we will be joined by keynote speakers including...

Dr Tim Farren

Dr Paul Harrison

Richard Alejo Blanco

Head of Immunophenotyping (SIHMDS) & Honorary Senior Lecturer at Barts and The London School of Medicine and Dentistry, Queen Mary University of London will be presenting Integrated diagnostics SIHMDS Case Studies.

Associate Professor at Institute of Inflammation and Ageing at the University of Birmingham will be presenting the Analysis of Preplatelets and Their Barbell Platelet Derivatives

by Imaging Flow Cytometry.

Principal Component Development Scientist, Component Development Laboratory, NHS Blood and Transplant, Cambridge will be focusing on XN Blood Bank Mode.

Take the opportunity to network with other delegates between presentations and at the end of each session. Visit our Expo booth areas to discover the latest Sysmex product and service updates.

Carol Briggs Award 2021

Programme Overview Tuesday 23rd November 2021: Haematology & General Interest Wednesday 24th November 2021: Mixed session Haematology & Haemostasis Thursday 25th November 2021: Haemostasis & General Interest

60 % 60%

60 % 60%

60 60%

%

Call for Posters!

To enter the competition, please email: usermeeting@sysmex.co.uk

REGISTER NOW 8

Sysmex Connect – October 2021

Sysmex Added Value Webinars

Save the Date

The Sysmex Added Value Webinar series have been a huge success and there is still time to register your place for the final webinars of the year.

Our mission to shape the advancement of healthcare has led Sysmex to providing tailor-made product solutions together with unrivalled service and support. These Added Value Webinars have been developed to support continual staff development and are perfectly suited to meet the changing demands of laboratories of the future. They are freely available for everyone and will provide further information on the added clinical value of Sysmex’s unique offering.

In addition, Sysmex UK is accredited by the IBMS and therefore attendance at a webinar can be submitted for CPD recognition!

Webinars from: 12pm – 1pm

IBMS Accreditated

OCTOBER 2021

Approved for CPD Recognition

Tuesday 21st October 2021: Added Value: CN-Series benefits in MDA and Mixing Studies NOVEMBER 2021

Thursday 11th November 2021: Added Value: Tracked Digital Morphology Tuesday 25th November 2021: Added Value: Caresphere™ LM

Register for the October and November 2021 Sysmex Added Value Webinars We would love to see you there!

To register, please visit:

www.uk.sysmex-academy.com There are a limited number of places available, please register your interest through Sysmex Academy or by contacting the ICS Department below: ICS_department@sysmex.co.uk

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Sysmex Connect – October 2021

A new vision for flow cytometry

CyFlow™ Monoclonal Antibodies

CE IVD and Research Monoclonal Antibodies.

Discover our expanded portfolio

Sysmex is proud to introduce CyFlow™ CE IVD high quality monoclonal antibodies with exceptional stability Distinctive separation between populations is a hallmark of the CyFlow™ Monoclonal Antibodies.

CyFlow™ CE IVD monoclonal antibody reagents Robust quality and high stain index

Core markers for complex flow cytometry applications

Ever-expanding selection of available specificities and fluorochrome conjugates Consistent test size for all fluorochromes

Backed by Sysmex applications and scientific staff

Fig. Human blood stained with CyFlow CE IVD antibodies and analysed by flow cytometry

DISCOVER OUR EXPANDED PORTFOLIO

Additional specificities and fluorochrome conjugates coming soon.

Download the CyFlow™ CE IVD Monoclonal Antibodies PDF

For more information on the Monoclonal Antibodies please contact flowcytometry@sysmex.co.uk

10

Visit our website to discover over 1000 antibody reagents.

ACCESS ANTIBODIES FINDER

Sysmex Connect – October 2021

New online PMI booking system Within the Service department we are always looking for ways to improve on our customer service.

One of the things we have been looking at is the booking of PMI’s (Preventative Maintenance Inspections) and that is where the new online PMI booking system comes into effect. Customers will be able to book the online PMIs for their analysers at a time that suits them without having to take a phone call from our service department. An email will be generated to the contact email address we have on our system, advising them of the analyser that is due and when it is due.

DOWNLOAD – HOW TO GUIDE

We are hoping that the new online booking system will help save time when it comes to booking PMI’s and give the customers a piece of mind that their analysers are being maintained as required.

If you have any queries, please contact the PMI scheduling team: pmischeduling@sysmex.co.uk

New standing order process At Sysmex we are always looking to improve customer satisfaction, customer service and move forward with the times.

We have created a new process for reagents standing orders. With this new process we aim for more automation and will set up alerts to inform our reagents team when your standing order is due to expire in 30 days. This will then be communicated with yourselves to start the new standing order for the next 12 months.

The new report will include: D etails of your account Previous 12 months usage Forecasted next 12-month usage (based on previous 12 months) New delivery schedule for the next 12 months Trend analysis

Benefits of this new standing order process will be: F aster turnaround time Will take into consideration your ad hoc orders so will have a more accurate forecast for the next 12 months Less ad hoc orders needing to be placed throughout the year Accuracy that should mean no amendments, with the flexibility to adapt to your changing needs

Q&A

What we may ask from you: T o provide a stock count onsite – This will help us have a rounded view of your stock requirements and adjust usage.

Make us aware of any changes in workload that you are aware of over the next 12 months.

Update the Reagents Team if the point of contact changes – This will help us ensure the data is sent to the correct person and dealt with in a timely manner.

so we anticipate that you will not need to change the schedule. If however you do need to make amendments, we would need this in an email to help us improve system accuracy in the future.

How do we update any information on the report?

What do we do if Sysmex have the wrong contact details for this process?

If you receive the report and any information is wrong, please contact the reagents team (reagents@sysmex.co.uk) with the corrected information and this will be updated our end.

If you are the incorrect contact, please respond back to the email advising us of the correct contact. This will then be updated on our system and should stop any further incorrect correspondence.

I have not received the report but I am the person who looks after the standing orders. What should I do?

Please contact your account manager who will update the reagents team with your details.

Can we amend the schedule?

The whole point of this new process and way of working is to capture any amendments that might be needed at an early stage,

If you have any questions, please do not hesitate to get in touch with the Reagents Team.

Phone: 0333 320 3470 Email: reagents@sysmex.co.uk 11

Sysmex Connect – October 2021

Get FIT for symptomatic CRC testing

FOB Gold

Faecal immunological testing (FIT) on most common clinical chemistry analysers

DOWNLOAD BROCHURE

12

Sysmex Connect – October 2021

Quantitative FIT on your existing clinical chemistry analyser

Many analyser models have been validated, e.g. Siemens Atellica®, Roche Cobas®, Beckman Coulter AU ®, and Abbott Alinity C®. For further information as to which analyser models have been validated, please contact your sales representative.

The FOB Gold System is a flexible and universal solution with all the major benefits of quantitative results and standardisation of FIT for an easy integration into your existing laboratory routine.

Quantitative FIT on your existing clinical chemistry analyser The FOB Gold System is a flexible and universal solution with all the major benefits of quantitative results and Keyofbenefits ofeasy the FOB Gold system standardisation FIT for an integration into your existing laboratory routine.

Highly sensitive haemoglobin detection with FOB Gold latex reagent No of dietary before testing nor drug interKey benefits therestrictions FOB Gold system ference upon analysis

H ighly sensitive haemoglobin detection with FOB Gold latex reagentQuantitative results with respective calibration curve allowbefore a defined cut-off value No dietary restrictions testing nor drug interference uponHigh analysis haemoglobin stability allows batch testing Quantitative results with respective calibration curve allow Flexible to match your throughput needs a defined cut-off value High haemoglobin stability allows batch testing Flexible to match your throughput needs

Many analyser models have been validated, e.g. Siemens Atellica®, Roche Cobas®, Beckman Coulter AU®, and Abbott Alinity C®. For further information as to which analyser models have been validated, please contact your sales representative.

FOB Gold

FOB Gold Tube Screen – unique, standardised stool sampling and direct analysis The patented, universally applicable FOB Gold tube ensures the perfect FIT for each routine laboratory, thanks to its unique set of features.

FOB Gold Tube Screen – unique, standardised stool sampling and direct analysis The patented, universally applicable FOB Gold tube ensures the perfect FIT for each routine laboratory, thanks to its unique set of features.

FOB Gold | 4 FOB Gold Tube Screen with screw cap and safety seal on bottom cap.

Separation septum ensures a standardised sample

Key benefits of the FOB Gold Tube Screen

ID barcode label for automatic reading.

F or direct and immediate use on clinical chemistry analysers 2-in-1 collection tube: easy, safe and hygienic Universal sample tube design makes it compatible with the majority of clinical chemistry analysers Directly ready for analysis upon arrival in the lab without sample preparation

Standardised stool sampling with the smartly designed collector tip.

FOB Gold Tube Screen For direct and immediate use on clinical chemistry analysers

haemoglobin stability: °C

Universal sample tube design makes it compatible with the majority of clinical chemistry analysers Directly ready for analysis upon arrival in the lab without sample preparation

Coming soon – Sysmex CaliaGold for clinical chemistry analysers Quantitative latex immunoassay for calprotectin measurement Particle-enhanced turbidimetric immunoassay (PETIA) Established cut-off in IBD diagnosis and monitoring Measuring range from 22 to 2200 µg/g The easiest and quickest procedure for faecal calprotectin quantification

Patient primary sampling with no further extraction required directly analysed on clinical chemistry analyser

For any further queries, please contact: pinn.philippa@sysmex.co.uk 13

Sysmex Connect – October 2021

The Digital Cell CellaVision Remote Review Software (CRRS) Most modern laboratories have a ‘quiet space’ for the examination of blood films – this could be a quiet corner, or even a separate room. So, when a lab has an automated track system with a DI-60 attached, it can be an issue for the morphologists who don’t want to stand in front of the analyser track to perform their smear examination. We have a solution to this problem that could help in more ways than one.

The Royal Preston Hospital has a Sysmex XN-9000 track with a DI-60 incorporated which has been validated for use by Steve Hambridge (Lead BMS Haematology), Nicola Peacock (BMS Team Leader Haematology) and Brittany Houghton (Haematology STP) with the support of the laboratory staff. The DI-60 uses version 6 software and the Advanced Red Cell Application, along with 5 remote review licence dongles. The laboratory uses digital morphology for smear examination during routine working hours with the long term aim to roll this out to 24-hour working.

Working in collaboration with CellaVision, laboratories can use CellaVision Remote Review Software (CRRS) to enable authorised users to log in to the software (using secure VPN) from other locations and access the results from the DI-60. CRRS makes it possible to review and verify cell differentials from anywhere, at any time, which removes the need to be by the analyser, or even in the laboratory itself.

Steve, can you briefly describe how the lab ran before you had digital imaging and what were the main limitations?

We have a dual site so we run principally from Royal Preston and our sister site is at Chorley hospital which is a smaller ESL. All of the blood films were sent across to Preston for manual analysis prior to the introduction of digital morphology. Realistically the main problems with blood film analysis is obviously the training aspect having the experienced personnel within the department to perform this labour intensive process.

CRRS allows users to step away from the analyser and review films in an area of their choice. It is very flexible and can be implemented to suit your own laboratories requirements. Some hospitals have it set up for a single site with a few users who perform morphology on a regular basis. Some will expand the CRRS to include the clinicians so that they have access in their office, in the clinic, and even have networked access for laptops so they can assist easily on call.

How does your digital morphology set up fulfil the needs of morphology within your laboratory?

Larger hospital networks use CRRS to connect multiple sites together.

CRRS allows external users from labs to remotely access CellaVision results. Films can be remotely reviewed, differentials can be performed and comments can be added using CRRS. This enhances a workflow efficiency, by removing geographical constraints; allowing an experienced morphologist to work remotely without travelling.

Consultants can review films easily without having to travel between sites and can also assist on-call/shift staff within the network. This is beneficial to the patients’ treatment, as cases can be reviewed quicker and allows for diagnosis to be made earlier.

We tend to work on the days digitalised images, cutting through arguably the easier elements to clear and focus on the ones that are urgent following that. Going forwards if this is done throughout a 24-hour period it will certainly improve things no end because literally you could be reviewing the film almost as it's been through the DI-60 in the future and picking it out if it needed to be reviewed manually or releasing those results fairly swiftly after generation.

Are there any users that utilise the remote review access for cross site working or from a remote location?

COVID-19 has highlighted a greater need for products like CRRS, and its usefulness will continue to benefit the lab when faced with staff shortages, by allowing staff to work remotely and to support one another during tough times.

The concept has been proved by the use of the laptop at home but cross sites we’ve just got a few little internal IT things to resolve before we can introduce the licences properly in Chorley. Once we've got those licences in operation across at our sister site then that will happen. The fact that we can have access via a laptop as well means arguably people can do this from home which with COVID has been a bit of a bonus as well.

CRRS comes in two varieties, either a dongle-based licence which is placed into the PC it is to be used on, or as a concurrent licence package that can be loaded onto a number of PCs. The benefit to the license package is that there are no physical dongles which can be lost when transferring the licence from one location to another.

14

Sysmex Connect – October 2021

Are there any features of the system you feel shine through for you?

I would say absolutely the quality of the image is exceptional and the actual categorisation again is usually very very good. With the additional advanced red cell parameters it does tend to suggest some of the features occurring a little bit more frequently than our eyes would see but that's for us to adjust the limitations of it and adjust the gateway's accordingly. I would say that's one of the shining lights, the other one realistically is the training because that really really helps, particularly with junior staff. They can sit with somebody a little bit more experienced, more senior and they can review images together and go through them. It's a good training tool in that respect and that is very very helpful as it's always probably one of the more difficult skills to pick up within the lab and certainly this has helped us no end.

How do the staff feel about using the digital morphology?

All staff have been impressed by the system but I would say certainly the younger ones have been like a duck to water with this, they've really embraced it easily. There's been a big buy-in, I would say the staff understand the methodology, it has stimulated their interest and it started them on the pathway to attaining good competencies in this area.

Nicola Peacock (BMS Team Leader Haematology) looking at remote review software in the morphology room at Royal Preston Hospital.

'I would say overall the ones that have been trained have really absorbed this and taken it up and it's been a positive benefit to the laboratory in that state.'

Steve Hambridge, Royal Preston haematology laboratory.

What advice would you give to anyone who was about to begin the process of implementing digital morphology?

Don't expect 100% compliance with digital to start with and use it as a tool in your armoury. It is a machine, it's not human and you've got to work within said limitations and it's important to realise that at the outset there are limitations with this and as long as you work within those boundaries you're not going to fall far short. Do a bit of background work with the guys at Sysmex and CellaVision, lean on their expertise, find out as much information as possible. If you can get the staff on board early doors and see some benefits then ultimately it makes it easier to bring into more routine use for sure and there are plenty of benefits there. As a training tool it's absolutely essential, it's brilliant, it really is good. We'd like to thank Kate at Wolverhampton for facilitating a visit there which really helped us make some plans moving forward and obviously Sysmex and CellaVision for the support that you provided.

Picture: Steve Hambridge (Lead BMS Haematology) and Tuli Panchal (BMS Haematology) in front of DI-60 in the Royal Preston haematology laboratory.

If you have any interesting images or case studies you wish to share or discuss, please get in touch via ICS_Department@sysmex.co.uk 15

Sysmex Connect – October 2021

Growing Your Knowledge Sysmex Scientific Focus

Sysmex is one of the world’s leading healthcare companies. We work hard to retain these distinctions. One of the ways we excel at what we do is by focusing on knowledge.

Sysmex stands out from other companies in our areas of expertise in terms of substantiated, scientific knowledge and its application. As we increase the clinical significance and applicability of our analyses, however, we fully appreciate the importance of providing comprehensive backgrounds and explanations. After all, while our findings can increasingly help clinicians and other specialists determine the root causes and developments of illnesses or other scientific investigations, this also means you, as our user, have to trust these findings.

The following papers provide the scientific and, where applicable, clinical backgrounds so you can make the most of our analysers in your daily work.

Sysmex Scientific Focus 1. A comparative evaluation of the CN-6000 haemostasis analyser using coagulation, amidolytic, immunoturbidometric and light transmission aggregometry assays 2. A performance evaluation of chemiluminescence enzyme immunoassays on the Sysmex CN-6500 haemostasis analyser Read the full articles on the next page

16

DOI: 10.1111/ijlh.13271

ORIGINAL ARTICLE

Sysmex Connect – October 2021

A comparative evaluation of the CN-6000 haemostasis analyser using amidolytic, immuno-turbidometric | coagulation, | and light transmission aggregometry assays

Received: 26 February 2020 Revised: 20 May 2020 Accepted: 31 May 2020 DOI: 10.1111/ijlh.13271

ORIGINAL ARTICLE

Chris Gardiner1 | Philip Lane1 | Katy Langley1 | Hitesh Tailor2 Samuel J. Machin1 | Ian J. Mackie1

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A comparative evaluation of the CN-6000 haemostasis analyser using coagulation, amidolytic, immuno-turbidometric Abstract and light transmission aggregometry assays Background: The CN-6000 (Sysmex Corp.) is a new haemostasis analyser with blood

1 Haemostasis Research Unit, University College London, London, UK 2 Haematology Evaluations Unit, HSL (Analytics) LLP, London, UK

Correspondence 1 Chris Gardiner, Haemostasis Research Unit, 1st Floor, 51 Chenies Mews, University 1 College London, London WC1E 6HX, UK. Email: chris.gardiner@uclmail.net

coagulation, amidolytic, immuno-turbidometric and light transmission aggregometry (LTA) capabilities. Transmitted light is monitored at multiple wavelengths (340, 405,

Chris Gardiner | Philip Lane1 | Katy Langley1 | Hitesh Tailor2 | 575, 660, 800 nm), from an LED light source.

1 Samuel J. Machin | Ian J. Mackie Aims: To evaluate the performance of the CN-6000 against a predicate device.

1

Haemostasis Research Unit, University College London, London, UK 2

Haematology Evaluations Unit, HSL (Analytics) LLP, London, UK Correspondence Chris Gardiner, Haemostasis Research Unit, 1st Floor, 51 Chenies Mews, University College London, London WC1E 6HX, UK. Email: chris.gardiner@uclmail.net

Methods: The CN-6000 was evaluated against the CS-5100 (Sysmex) for 14 different tests, using 880 samples from normal subjects, anticoagulated patients, critically ill

Abstract

patients, plasmas with high or low fibrinogen content or abnormal levels of interferBackground: The CN-6000 (Sysmex Corp.) is a new haemostasis analyser with blood ing substances. Between-day assay imprecision was assessed using commercial QC coagulation, amidolytic, immuno-turbidometric and light transmission aggregometry materials (n = 10 replicates on each of 5 days).

(LTA) capabilities. Transmitted light is monitored at multiple wavelengths (340, 405, Results: Acceptable levels of imprecision were obtained for all assays. Agreement 575, 660, 800 nm), from an LED light source. between the two analysers was excellent for all assays. Throughput was 35% higher Aims: To evaluate the performance of the CN-6000 against a predicate device. using the CN-6000 (337 vs 250 tests per hour for PT, aPTT and fibrinogen). The Methods: The CN-6000 was evaluated against the CS-5100 (Sysmex) for 14 different CN-6000 also demonstrated improved clot detection in plasmas with high levels of tests, using 880 samples from normal subjects, anticoagulated patients, critically ill interfering substances as demonstrated by a 29% reduction in “vote-outs” due to low patients, plasmas with high or low fibrinogen content or abnormal levels of interferlight transmission (24 vs 34). ing substances. Between-day assay imprecision was assessed using commercial QC Conclusions: The CN-6000 demonstrated excellent comparability with the predimaterials (n = 10 replicates on each of 5 days). cate instrument and acceptable levels of imprecision in all assays. Improvements in Results: Acceptable levels of imprecision were obtained for all assays. Agreement throughput and clot detection in the presence of interfering substances were also between the two analysers was excellent for all assays. Throughput was 35% higher shown. using the CN-6000 (337 vs 250 tests per hour for PT, aPTT and fibrinogen). The CN-6000 also KEYWORD S demonstrated improved clot detection in plasmas with high levels of coagulation, substances laboratory automation, laboratory interfering as demonstrated by practice a 29% reduction in “vote-outs” due to low

light transmission (24 vs 34).

Conclusions: The CN-6000 demonstrated excellent comparability with the predicate instrument and acceptable levels of imprecision in all assays. Improvements in throughput and clot detection in the presence of interfering substances were also shown.

KEYWORDS This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, coagulation, laboratory automation, laboratory practice provided the original work is properly cited. © 2020 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd

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wileyonlinelibrary.com/journal/ijlh 643

Int J Lab Hematol. 2020;42:643–649.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd Int J Lab Hematol. 2020;42:643–649.

17

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1 | I NTRO D U C TI O N

TA B L E 1 Reagents and calibrators used on the CN-6000 and CS-5100

Clinical laboratories are under increasing pressure to eliminate

Test

errors and reduce turnaround time to improve patient outcomes,

Prothrombin time/INR

while reducing costs. This is largely achieved through laboratory automation, with increasingly complex analysers performing an expanding range of tests but with reduced operator dependency.

Haemostasis testing relies on several different technologies, and some specialist tests (eg platelet aggregation) have proved difficult to automate. The trend towards centralized multidisciplinary blood sciences laboratories and fewer specialist haemostasis tech-

ence by haemolysis, icterus and lipaemia (HIL checking). There has also been a drive towards smaller blood collection tubes and lower sample dead volume, which is necessary to avoid iatrogenic anaemia2 and is essential for analysing paediatric samples. Space in clinical laboratories is often limited, and in many core laboratories, it is essential that any new analyser can be incorporated into the laboratory's track system.

The CN-6000 (Sysmex Corp) is a new high throughput, cap-piercing haemostasis analyser with blood coagulation, amidolytic, immuno-turbidometric and light transmission aggregometry capabilities.

Transmitted light is monitored at multiple wavelengths (340, 405, 575, 660, 800 nm), from an LED light source, which combined with improved clot detection algorithms is intended to reduce sample rejection due to optical interference by HIL through wavelength switching and automatic high gain detection settings. It also has a

Dade Innovin ®

®

®

AK Calibrant

Dade Actin FS

Standard Human Plasma

Clauss fibrinogen

Dade® Thrombin Reagent

Standard Human Plasma

Thrombin time

Test Thrombin Reagent

Standard Human Plasma

Factor VIII

Dade® Actin® FS FVIII deficient plasma

Standard Human Plasma

Factor XIII

Berichrom® Factor XIII assay

Standard Human Plasma

Antithrombin

Innovance® Antithrombin

Standard Human Plasma

D-Dimer

Innovance® D-dimer

D-Dimer Calibrant

VWF Activity

Innovance® VWF Ac assay

Standard Human Plasma

VWF ristocetin cofactor activity

BC von Willebrand Reagent

Standard Human Plasma

Rivaroxaban (anti-Xa activity)

Biophen™ Dixal Rivaroxaban

Rivaroxaban calibrator

Apixaban (anti-Xa activity)

Biophen™ Dixal Apixaban

Apixaban calibrator

Edoxaban (anti-Xa activity)

Biophen™ Dixal Edoxaban

Edoxaban calibrator

Dabigatran (Antithrombin activity)

Biophen™ DTI

Dabigatran calibrator

stasis analysers capable of performing simultaneous testing using sess sample quality by checking for fill volume, optical interfer-

Calibrators

®

Activated partial thromboplastin time

nologists has driven the development of multi-parameter haemoseveral methodologies.1 Many of these instruments routinely as-

Reagent

relatively small footprint (CN-6000; 720 × 906 × 1350 cm vs CS5100; 1030 × 1150 × 1280 cm) and can readily be incorporated into

were also tested. Informed consent was obtained from normal do-

a track system.

nors (approved by the UCL Research Ethics committee: Project ID

The purpose of this study was to compare the performance of

Number: 7029/001). In total, 880 samples from normal subjects,

the CN-6000 haemostasis analyser against the predicate device

patients receiving warfarin, low molecular weight heparin (LMWH)

(CS-5100 system) for assays using clotting, amidolytic, immunotur-

or direct oral anticoagulants (rivaroxaban, apixaban, edoxaban and

bidimetric and light transmission aggregometry (VWF ristocetin co-

dabigatran), as well as patients with critical illness, lupus anticoagu-

3-5

using reagents recommended by

lant, haemophilia A or von Willebrand disease (vWD), and samples

the manufacturer (Table 1). The protocol was designed using pub-

with low or high fibrinogen levels, high levels of haemolysis, icterus

lished guidelines.6,7 This included an assessment of precision, com-

or lipaemia were tested.

factor assays) methodologies,

Due to limited clinical sample availability, citrated whole blood

parability, carryover, HIL checking and throughput.

from several normal donors was spiked with unfractionated heparin (5000 IU/mL Multiparin; Wockhardt UK Ltd) before plasma prepara-

2 | M E TH O DS

tion and dilution with autologous unspiked plasma to yield a range of concentrations. As dabigatran is seldom used in the UK, external

Citrated plasma was obtained from residual, anonymized samples

quality control samples, quality control (QC) samples and normal

(collected into 0.109 mol/L sodium citrate (Vacutainer; Becton

plasma were used to prepare plasmas with a range of dabigatran

Dickinson) after all routine testing had been completed, in compli-

concentrations.

ance with local ethical committee rules and the Human Tissue Act.

Clotting tests (PT, APTT, fibrinogen and Factor VIII), amidolytic

Samples were frozen at −80°C and thawed at 37°C immediately

(factor XIII, antithrombin, anti-Xa, direct thrombin inhibitor, and an-

prior to testing. Normal citrated plasma collected locally from ap-

ti-Xa DOAC), immuno-turbidometric (VWF activity and D-dimer)

parently normal healthy volunteers and commercially sourced

and light transmission aggregometry (VWF ristocetin cofactor assay)

plasmas (CRYOcheck™ Normal Donor Set; Precision BioLogic Inc)

methodologies were evaluated.

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GARDINER Et Al.

TA B L E 2 Between-day imprecision for the CS-5100 and CN-6000 analysers. 10 replicates of each control were performed on at least 5 different days

CS-5100

CN-6000

Test

Control

Mean

Prothrombin time (s)

Citrol 1

11.1

0.2

Citrol 2

30.3

Citrol 3

49.8

SD

CV (%)

Mean

SD

CV (%)

1.6

11.1

0.1

1.3

0.4

1.5

30.4

0.4

1.4

1.4

2.8

49.8

1.1

2.2

Activated partial thromboplastin time (s)

Citrol 1

24.9

0.2

0.9

25.0

0.3

1.1

Citrol 2

46.0

0.8

1.6

46.2

0.8

1.7

Citrol 3

72.5

72.4

Clauss fibrinogen (g/L)

Control N

Thrombin time (s)

2.83

0.7

1.0

0.11

4.1

0.7

0.9

2.72

0.14

5.0

Control P

1.01

0.11

11.0

0.93

0.07

8.1

High fbg pool

6.62

0.26

3.9

6.48

0.25

3.9

Control N

19.5

0.4

2.1

19.4

0.5

2.8

Control P

25.4

1.9

7.6

25.1

1.0

4.0

Heparin low control

33.6

4.4

13.2

33.8

4.1

12.1

Factor VIII (IU/dL)

Control N

93.3

2.2

2.3

91.6

2.7

3.0

Control P

31.4

0.5

1.5

32.4

0.7

2.0

Factor XIII (IU/dL)

Control N

85.9

3.5

4.0

88.7

2.8

3.2

Control P

31.0

2.2

7.2

31.9

1.4

4.5

Control N

95.8

1.0

1.1

96.6

1.2

1.3

Control P

32.7

33.7

Antithrombin (IU/ dL) D-dimer mg/L FEU

0.9

2.6

1.1

3.2

D-dimer control I

0.30

0.02

5.5

0.32

0.07

3.2

D-dimer control 2

2.59

0.17

6.5

2.76

0.07

3.2

6.7

6.6

103.8

4.6

4.5

VWF activity (IU/ dL)

Control N

101.3

Control P

28.3

2.0

6.9

28.6

1.5

5.3

VWF ristocetin cofactor

Control N

88.9

8.1

9.0

87.3

7.6

8.8

(IU/dL)

Control P

24.4

2.4

9.8

24.8

2.4

9.6

Rivaroxaban (ng/ mL)

Rivaroxaban C1

111.8

3.9

3.5

111.8

4.4

3.6

Rivaroxaban C2

325.7

4.8

1.5

330.3

8.8

2.6

Apixaban C1

354.7

24.7

7.0

373.0

20.2

5.4

Apixaban C2

158.9

7.6

4.8

167.7

9.3

5.5

Edoxaban C1

329.3

7.7

2.4

333.3

8.8

2.6

Edoxaban C2

158.9

7.6

4.8

167.7

9.3

5.5

Dabigatran C1

317.5

5.0

1.6

308.5

9.6

3.1

Dabigatran C2

106.1

4.4

4.4

105.8

5.7

5.4

Apixaban (ng/mL) Edoxaban (ng/mL) Dabigatran (ng/mL)

Standard curve reproducibility was studied by performing cal-

For the comparability study, samples were tested on the CS-

ibrations on five different days using the reagents and calibrators

5100 and CN-6000 within the same 2-hour period. The same re-

shown in Table 1 (All reagents from Siemens Healthcare, Marburg,

agents and redilution limits were used on both instruments. FVIII

Germany). Imprecision was assessed by testing freshly reconstituted

assays were performed in multidilution analysis mode (MDA) using

lyophilized quality control (QC) samples ten times on five separate

low normal or high dilution ranges to ensure that the clotting times

days. The QC plasmas used for each test are listed in Table 2.

were on the linear part of the calibration curve, and the mean of the

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GARDINER Et Al.

3 | R E S U LT S

three measured FVIII concentrations was reported. Von Willebrand factor (VWF:Ac) activity was measured using normal (25 - 600 IU/ mL) or low (0-25 IU/mL) calibration curves as appropriate. The di-

The between-run coefficient of variation (CV) for calibration curve

lution used to assay von Willebrand ristocetin cofactor (VWF:RCo)

imprecision for PT, Clauss fibrinogen, D-dimer, antithrombin, da-

was guided by the VWF:Ac result.

bigatran and FVIII assays was <3.0%. The CVs for the calibration

Cholesterol and triglycerides were measured using Chol2 and tri-

curves for rivaroxaban, apixaban and edoxaban anti-Xa assays

glyceride reagents using a Cobas C111 analyser (Roche Diagnostics).

were all <5%. Between-run calibration curve CVs for VWF:Ac and

Plasma haemoglobin was measured using the Hemocue system

VWF:RCo were <10% and <15%, respectively.

(Radiometer).

The between assay imprecision results are shown in Table 2. In

Sample and reagent carryover were investigated as previously

all cases, the %CV values for both instruments were lower than the

described6 Briefly, sample carryover was assessed by performing

manufacturer's specifications for within-run imprecision for a nor-

APTT testing on aliquots of normal plasma (A1-A3) and plasma con-

mal control plasma for the CS-5100.

taining 1 IU/mL unfractionated heparin (B1-B3) in the sequence A1,

The performance of the HIL checking function was assessed by

A2, A3, B1, B2, B3 ten times, then repeating the sequence in reverse.

testing 40 normal, 30 icteric, 30 haemolysed and 40 lipaemic sam-

Reagent carryover was investigated by performing APTT testing on

ples. Lipaemia was defined as triglycerides of >1.88 mmol/L or cho-

five aliquots of normal plasma before performing Clauss fibrinogen

lesterol of >5.2 mmol/L, haemolysis as plasma Hb of >0.5 g/L, and

assays on the same five aliquots. This sequence was repeated ten

icterus as bilirubin >17 µmol/L. As very high levels of any interfering

times.

substance will trigger all three HIL flags, sensitivity and specificity

Statistical analysis was performed with GraphPad Prism version

was assessed by testing the ability of the analysers to trigger HIL

8.0.0 for Windows (GraphPad Software). Deming regression analysis

flags in the presence of lipaemia, haemolysis or icterus. The sensitiv-

and Bland Altman analysis were performed to assess comparability.

ity of both instruments to HIL was 96.9%. The CS-5100 generated

F I G U R E 1 Regression graphs for CS-5100 vs CN-6000. A, prothrombin time, B, activated partial thromboplastin time, C, thrombin time, D, Clauss Fibrinogen

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GARDINER Et Al.

F I G U R E 2 Altman Bland plots for A, prothrombin time, B, activated partial thromboplastin time, C, thrombin time, D, Clauss Fibrinogen

HIL flags in the absence of any HIL in 4 samples while the CN-6000

HIL). Good agreement was observed between methods. Optical

had only one false flag, resulting in specificity of 90.7% and 97.7%,

interference was observed in seven lipaemic samples (triglyceride

respectively.

>8.0 mmol/L) on both instruments. Haemolysis (plasma Hb 0.519 g/L) and icterus (bilirubin 20-493 µmol/L) did not cause optical

Comparability for PT was assessed in 389 samples includ-

interference.

ing normal plasmas, plasma from patients receiving warfarin and DOACs, and plasmas with high levels of HIL. Excellent agreement

APTT measurements performed on 362 samples including

was obtained between the methods with no obvious trend with

plasmas from normal subjects, patients receiving LMWH, UFH or

increasing PT (Figures 1 and 2, Table 3). 10/40 and 6/40 lipaemic

DOACs, patients with haemophilia, vWD, or lupus anticoagulant,

samples failed to give PT results with the CS-5100 and CN-6000

and plasmas with high levels of HIL also showed excellent agree-

analysers, respectively (triglycerides 4.1 - 19.6 mmol/mL, cholesterol

ment. No optical interference was observed in 40 lipaemic plasmas

4.01-9.68 mmol/L). All samples with triglyceride concentrations of

(triglyceride 1.4-12.4 mmol/L, cholesterol 3.9-9.78 mmol/L), 30

<8 mmol/L gave PT results on the CN-6000. Two of 30 haemolysed

icteric plasmas (20-265 µmol/L) or 30 haemolysed plasmas (plasma

samples with plasma haemoglobin levels of 8.4 and 19 g/L failed to

Hb 1.3-25.6 g/L).

give results with either instrument. No optical interference due to

A range of plasmas were used to assess comparability for

icterus was observed in PT performed on 30 icteric samples (bili-

FVIII, FXIII, vWF:Ac, vWF:RCo, DOACs, D-dimer and antithrombin

rubin 20-493 µmol/L). Clauss fibrinogen assays performed on 327

(Table 3). Only samples giving results within the reportable range

of the same plasmas also showed good agreement. Optical interfer-

for both instruments were used for the analysis. Consequently, al-

ence occurred in two lipaemic samples (triglycerides >10.0 mmol/L)

though large numbers of samples (180-300) were tested, some tests

with both instruments, but no interference due to icterus or haemo-

produced many results outside the reportable range (eg DOAC and.

lysis was observed.

VWF:RCo) and regression analysis was performed on a relatively small number of results. Despite this, r2 values of >0.9 were reported

Thrombin time comparability was assessed in 259 samples (including normal plasmas, plasmas with high levels of D-dimer and

for all tests except VWF:RCo (Table 3).

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GARDINER Et Al.

TA B L E 3 Regression parameters and correlation coefficients for CS-5100 vs CN-6000. Only samples giving results with both instruments were used Mean CS-5100

Mean CN-6000

Range CS-5100

n

Slope

Intercept

R2

Prothrombin time (s)

374

1.007

−0.020

0.999

18.51

18.58

9.9-73.3

APTT (s)

362

1.013

−0.309

0.993

32.74

32.93

19.3-290.4

Thrombin time (s)

252

0.992

0.101

0.990

19.57

19.53

12.9-92.7

Clauss fibrinogen (g/L)

325

0.987

−0.027

0.986

3.74

3.67

Factor VIII (IU/mL)

204

0.996

0.136

0.996

108.0

107.3

1.5-456.0

Factor XIII (IU/mL)

165

0.969

4.343

0.971

87.3

89.2

1.3-183.3

83.3

83.5

18.6-148.9

Test

Antithrombin (IU/mL)

197

1.037

−2.182

0.997

D-dimer mg/L FEU

234

0.898

0.059

0.993

1.75

1.86

0.65-11.28

0.19-25.75

VWF activity (IU/mL)

148

0.977

4.298

0.994

150.8

151.7.

4.5-538.9

VWF ristocetin cofactor (IU/ mL)

123

0.976

3.530

0.887

105.4

106.4

12.1-274.4

Rivaroxaban (ng/mL)

28

0.982

1.693

0.994

183.1

181.4

39.4-425.4

Apixaban (ng/mL)

25

0.901

8.345

0.973

157.3

150.1

60.4-264.9

Edoxaban (ng/mL)

12

1.073

−37.0

0.986

203.4

181.3

97.4-475.0

Dabigatran (ng/mL)

28

0.960

9.27

0.994

258.8

247.2

60.7-532.0

Throughput was assessed by testing PT, APTT and fibrinogen in

HIL flagging was assessed in 140 samples. Although HIL flag-

60 plasma samples representative of a typical hospital laboratory

ging is only an approximation of haemolysis, icterus and lipaemia

workload. Testing was performed in cap-piercing mode, with auto-

based on light transmission, both instruments demonstrated a sen-

matic reflex testing for samples with fibrinogen results outside the

sitivity of 96.9% to optical interference due to HIL. However, the

redilution points (<0.8 g/L and > 4.5 g/L). The throughput of the CN-

CN-6000 showed improved specificity to HIL (97.7% vs 90.7% for

6000 was 337 test/hour versus 250 test/hour for the CS-5100. No

the CN-6000 and CS-5100, respectively). Importantly, haemolysis

reagent or sample carryover was detected.

and lipaemia were flagged at levels previously reported to cause clinically important discrepancies in some coagulation tests.8-10 No sample or reagent carryover was detected, and the throughput of

4 | D I S CU S S I O N

the CN-6000 was 35% higher than the CS-5100 in sample representative of a normal hospital laboratory workload. This is the result of

The purpose of this study was to compare the performance of the

an improved high-pressure rinsing system, which reduced the time

CN-6000 haemostasis analyser with the established CS-5100 system

for pipette rinsing.

for assays using clotting, amidolytic, immunoturbidimetric and light

We did not evaluate LTA on fresh platelets in this study, as quan-

transmission aggregometry (VWF ristocetin cofactor assays) meth-

titative comparative evaluation of LTA is extremely difficult. There

odologies. Intra-assay imprecision for both analysers was within the

are no standards, no quality control materials and fresh platelets are

manufacturer's specification for the CS-5100 and similar to previous

labile. For this reason, VWF:RCo with freeze-dried platelets was se-

studies of the CS-5100.3-5 Agreement between the two analysers

lected to evaluate the LTA measurement feature on the CN-6000.

was excellent for the 14 assays studied in a wide range of samples.

However, we acknowledge that formalin-fixed platelets do not be-

Optical interference was observed in some tests in a few samples

have in the same way as fresh platelets, and this is a limitation of

with exceptionally high levels of lipaemia (triglyceride > 8 mmol/L)

this study.

and haemolysis (plasma Hb > 8.4 g/L). When errors related to the

In conclusion, the CN-6000 demonstrated excellent comparabil-

amount of transmitted light (Turbidity Level Over, Trans Light High,

ity with the predicate instrument and acceptable levels of impreci-

No Coagulation and Slight Coagulation) due to the influence of inter-

sion in all assays, with improved throughput and HIL detection.

fering substances (eg HIL) are generated, the CN-6000 automatically switches to high gain. If the errors are still present, the detection

C O N FL I C T O F I N T E R E S T

wavelength is switched for clotting tests only, for example PT 660-

The work was supported by an institutional, unrestricted research

800 nm. This resulted in a slight reduction in samples for which re-

grant from Sysmex UK Ltd. However, Sysmex had no part in the data

sults could not be obtained, with the CN-6000. All samples with HIL

analysis or preparation of the manuscript. CG, IJM and SJM are con-

levels within the manufacturer's specified limits gave results.

sultants for Sysmex Corp.

22

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GARDINER Et Al.

AU T H O R C O N T R I B U T I O N S CG designed the study, performed assays, analysed the data and

6.

wrote the manuscript. PL, KL and HT performed assays and analysed data. SJM and IJM designed the study, aided in data analysis and

7.

critically reviewed the manuscript.

ORCID Chris Gardiner

8.

https://orcid.org/0000-0002-2318-0062

Hitesh Tailor

https://orcid.org/0000-0003-3615-7889

Ian J. Mackie

https://orcid.org/0000-0002-7393-2365

9.

REFERENCES

10.

1. Lippi G, Plebani M, Favaloro EJ. The changing face of hemostasis testing in modern laboratories: consolidation, automation, and beyond. Semin Thromb Hemost. 2015;41(3):294-299.

2. Stefanini M. Iatrogenic anemia (can it be prevented?). J Thromb Haemost. 2014;12(10):1591.

3. Chen L, Chen Y. Performance evaluation of the sysmex CS-5100 automated coagulation analyzer. Clin Lab. 2015;61(7):653-660.

4. Flieder T, Gripp T, Knabbe C, Birschmann I. The Sysmex CS-5100 coagulation analyzer offers comparable analytical performance and excellent throughput capabilities. Pract Lab Med. 2016;6:38-47.

5. Ratzinger F, Schmetterer KG, Haslacher H, Perkmann T, Belik S, Quehenberger P. Evaluation of the automated coagulation analyzer

CS-5100 and its utility in high throughput laboratories. Clin Chem Lab Med. 2014;52(8):1193-1202.

CLSI. H57A Protocol for the Evaluation, Validation, and Implementation of Coagulometers. Approved Guideline.

2008;28(4).

Gardiner C, Kitchen S, Dauer RJ, Kottke-Marchant K. Adcock DM. Recommendations for evaluation of coagulation analyzers. Lab Hematol. 2006;12(1):32-38.

Hernaningsih Y, Akualing JS. The effects of hemolysis on plasma prothrombin time and activated partial thromboplastin time tests using photo-optical method. Medicine (Baltimore). 2017;96(38):e7976.

Woolley A, Golmard J-L, Kitchen S. Effects of haemolysis, icterus and lipaemia on coagulation tests as performed on Stago STACompact-Max analyser. Int J Lab Hematol. 2016;38(4):375-388.

Gardiner C, Lane P, Tailor H, Mackie IJ. A practical method for reducing the interference due to lipaemia in coagulation tests. Int J Lab Hematol. 2020;42(2):140-144.

How to cite this article: Gardiner C, Lane P, Langley K, Tailor H, Machin SJ, Mackie IJ. A comparative evaluation of the CN-6000 haemostasis analyser using coagulation, amidolytic, immuno-turbidometric and light transmission aggregometry assays. Int J Lab Hematol. 2020;42:643–649. https://doi. org/10.1111/ijlh.13271

23

DOI: 10.1111/ijlh.13656

ORIGINAL ARTICLE

Sysmex Connect – October 2021

A performance evaluation of chemiluminescence enzyme immunoassays on the Sysmex CN-6500 haemostasis analyser Chris Gardiner1,2 Ian J. Mackie1

| Philip Lane1 | Hitesh Tailor3

| Samuel J. Machin1 |

1 Research Department of Haematology, University College London, London, UK

Abstract

2

Background: The Sysmex CN-6500 is a new haemostasis analyser with an integrated

Chris Gardiner Consulting Ltd. Aylesbury, Buckinghamshire, UK 3

Haematology Evaluations Unit, HSL (Analytics) LLP, London, UK Correspondence Chris Gardiner, Chris Gardiner Consulting Ltd, Aylesbury, Buckinghamshire, HP17 8JP. UK. Email: chris.gardiner@uclmail.net

immunoassay module that performs chemiluminescence enzyme assay (CLEIA) in addition to coagulation, turbidimetric, chromogenic and platelet aggregation tests.

Aims: To evaluate the analytical performance of the CN-6500 against the predicate device (Sysmex HISCL-800) for soluble thrombomodulin (TM), thrombin-antithrombin (TAT), tissue plasminogen activator/plasminogen activator inhibitor 1 complex (tPAIC) and plasmin α2 plasmin inhibitor complex (PIC) assays.

Methods: Imprecision was assessed by testing two levels of quality control plasmas 10 times on 5 separate days. Comparability was studied in 230 plasmas from normal donors (n = 30), patients with suspected disseminated intravascular coagulation (DIC, n = 100), sepsis (n = 20) or liver disease (n = 20), lipaemic (n = 20), haemolysed (n = 20) and icteric samples (n = 20). Limit of detection, limit of quantitation and linearity were determined by testing serial dilutions of normal plasma. Sample carryover was assessed by testing samples with high and low normal levels of the analytes concerned.

Results: The CN-6500 performed 21 CLEIA tests per hour, while simultaneously performing coagulation tests. Acceptable between-run imprecision was obtained using commercial controls with normal and high activity for each analyte (%CV <4%), for all four assays. Excellent linearity was observed (slope 0.89-1.03; r2 >0.99) across

the measurement range. The lower limits of detection and quantitation were as follows: TM <0.3/0.6 TU/ml, TAT >0.1/<0.2 ng/ml, PIC <0.004/<0.008 µg/ml and tPAI-C < 0.01/<0.1 ng/ml, respectively. All four assays showed excellent correlation between analysers and were unaffected by haemolysis, icterus or lipaemia. No carryover was observed.

Conclusions: Our data demonstrate that the performance of the CLEIA assays on the CN-6500 is comparable to that of a stand-alone immunoassay analyser.

KEYWORDS

coagulation, DIC, fibrinolysis, laboratory automation

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2021 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.

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wileyonlinelibrary.com/journal/ijlh 1

Int J Lab Hematol. 2021;00:1–6.

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GARDINER Et Al.

1 | I NTRO D U C TI O N

beads, the ALP chemiluminescent substrate (CDP-Star®) was added and luminescence intensity measured. TAT and tPAI-C were reported in ng/ml, TM was reported in TU/ml (thrombomodulin units),

The Sysmex CN-series (Sysmex Corporation) is a range of highthroughput compact haemostasis analysers.1 The CN-6500 analyser

and PIC was reported in µg/ml, as per the manufacturer's instruc-

has an integral immunoassay module which performs chemilumi-

tions. Precision was assessed using Controls L and H (normal and

nescence enzyme immunoassays (CLEIA) in addition to coagulation,

high QC materials) provided by the manufacturer tested 10 times on

chromogenic, immunoturbidometric and light transmission platelet

each of 5 separate days.

aggregometry testing. CLEIA is an immunoassay technique in which

Citrated plasma was obtained from residual, anonymized sam-

the label is a luminescent molecule. It typically offers a wide linear

ples (collected into 0.109 mol/L sodium citrate (Vacutainer; Becton

measurement range, with a high signal intensity, and an absence of

Dickinson) after all routine testing had been completed, in compli-

interference, resulting in high sensitivity and specificity. 2 In common

ance with local ethical committee rules and the Human Tissues Act

with other automated CLEIA systems, the CS-6500 is much faster

2004 (UK). Samples were frozen at −8°C and thawed in a 37°C water

than traditional immunoassays.

bath immediately prior to testing. Normal citrated plasma collected

The CN-6500 currently has four CLEIA assays available; soluble

locally from apparently normal healthy volunteers and commer-

thrombomodulin (TM), thrombin-antithrombin (TAT), tissue plasmin-

cially sourced plasmas (CRYOcheck™ Normal Donor Set; Precision

ogen activator/plasminogen activator inhibitor 1 complex (tPAI-C)

BioLogic Inc) were also tested. Informed consent was obtained from

and plasmin/α2 plasmin inhibitor complex (PIC). The performance

normal donors (approved by the UCL Research Ethics committee:

of these assays has previously been evaluated on the HISCL-5000

Project ID Number: 7029/001).

(Sysmex Corporation),3 a stand-alone fully automated rapid immu-

Linearity, lower limit of detection (LLoD) and lower limit of quan-

nochemistry system which utilizes CLEIA technology. The HISCL

titation (LLoQ) were determined by serial dilution of pathological

system uses biotinylated primary antibodies, streptavidin-coated

plasma samples in assay diluent across the reportable range. For

magnetic beads, alkaline phosphatase (ALP) labelled secondary anti-

LLoD and LLoQ determination, each dilution was tested six times.

bodies and an ALP chemiluminescent substrate (CDP-Star®). These

The LLoD was the lowest concentration showing a statistically sig-

assays are reported to have clinical utility in the diagnosis of dis-

nificant difference from the assay blank. This was achieved by de-

seminated intravascular coagulation (DIC) and its subtypes.3-5 They

termining the mean concentration at each dilution and performing a

6

also have potential applications in cancer medicine. The diagnostic

T test relative to six blank measurements. The LLoQ was the lowest

criteria for DIC proposed by the Japanese Society for Thrombosis

concentration which gave a %CV of <10%).

Sample carryover was investigated as previously described.11

and Haemostasis recognize different subtypes of DIC, which reflect 4

fibrinolytic status. Consequently, the measurement of TAT and PIC

Briefly, aliquots of normal plasma (A1-A3) and plasma containing

is frequently included in the diagnostic workup for DIC in Japanese

high levels of the analyte of interest (B1-B3) were tested in the se-

laboratories. Endogenous soluble TM may be assayed as a marker of

quence A1, A2, A3, B1, B2, B3 five times, then repeated with the

endothelial injury, as it is cleaved and released from the vessel wall

sequence in reverse.

in many inflammatory conditions.7 tPAI-C may also be a useful assay

Unfractionated heparin (5000 IU/ml Multiparin, Wockhardt UK

in the investigation of DIC, and increased levels are associated with

Ltd) was added to samples at 2.0 U/ml and compared with the un-

multiorgan failure.8 More recently, it has been observed that TM,

adulterated samples to study possible interference.

TAT, PIC and tPAI-C may have prognostic value in assessing patients

Comparability was assessed in 230 plasmas from normal donors

with cancer6 COVID-19.9,10

(n = 30), patients with suspected DIC (n = 100), sepsis (n = 20), liver

The purpose of this study was to compare the performance of

disease (n = 20), lipaemia (n = 20), haemolysis (n = 20) and icterus

four CLEIA tests on the CN-6500 haemostasis analyser against the

(n = 20). The samples from patients suspected DIC were from the

same reagents on the predicate device (HISCL-800).

intensive therapy unit (ITU) with low platelet counts. Samples with haemolysis, icterus or lipaemia were selected by visual inspection.

Plasma haemoglobin was assayed using the HemoCue system

2 | M E TH O DS

(Radiometer). Cholesterol and triglycerides were measured using Chol2 and triglyceride reagents using a Cobas C 111 analyser (Roche Diagnostics).

The analytical performance of the CN-CLEIA system was compared with that of a stand-alone immunoanalyser (Sysmex HISCL-800) for

Throughput was assessed by three different exercises. All

TM, TAT, PIC and tPAI-C.6,7 The CN-6500 performed the CLEIA

throughput exercises were started from when the instrument was at

method as follows: 10-30μl of sample was incubated with a primary

rest, in reflex testing mode.

biotinylated antibody in the liquid phase to allow antibody-antigen • measurement of TM, TAT, PIC and tPAI-C alone in 12 samples

binding. Streptavidin-coated magnetic beads were added to bind

from patients on ITU

antibodies, and free antigen was removed by washing. Following a brief incubation with an ALP labelled secondary, unbound secondary

• simultaneous measurement of the four CLEIA methods, plus pro-

antibody is removed by washing. Buffer was added to disperse the

thrombin time (PT), activated partial thromboplastin time (APTT),

25

Clauss fibrinogen assay (Fib) and D-dimer (Innovin®, Actin® FS,

concentration. Excellent linearity was observed for all four as-

Thrombin Reagent and INNOVANCE® D-dimer, all Siemens, across the reportable range, with r2 values of 0.998 or better Sysmex Connect –says October 2021 Marburg, Germany) in 12 samples from patients on ITU

(Figure 1). The lower limit of quantitation (LLoQ) for TM, TAT, PIC

• measurement of PT, APTT, Fib and D-dimer only on 12 samples

and tPAI-C was 0.6 TU/ml, 0.2 ng/ml, 0.008 μg/ml and 0.1 ng/ml,

from patients on ITU

respectively. Lower limit of detection (LLoD) was 0.3 TU/ml, 0.1 ng/

• PT, APTT, Fib and D-dimer in 100 samples selected at random

ml, 0.004 μg/ml and 0.01 ng/ml.

from the clinical workload.

Optical interference was assessed in 60 samples with lipaemia, icterus or haemolysis with triglycerides up to 26.1 mmol/L, choles-

Statistical analysis was performed with GraphPad Prism version

terol up to 10.3 mmol/L, bilirubin up to 531 μmol/L and haemoglo-

9.0.0 for Windows (GraphPad Software). Reference intervals were

bin up to 15.5 g/L. No optical interference was evident, with good

calculated as the 2.5th-97.5th percentiles after determining that the

agreement between the two methods, and results were obtained for

data had a non-normal distribution. Comparability was assessed by

TM, TAT PIC, and tPAI-C in all 60 samples. Activation in two haemo-

Deming regression analysis, and non-parametric methods were used

lysed samples caused unstable levels of TAT, and these samples were

throughout. Probability values (P) <.05 were considered statistically

excluded from the analysis. In vitro haemolysis is known to be associated with activation of the coagulation pathways.13 No significant

significant. Systemic bias was obtained by Bland-Altman analysis.

sample carryover was detected in the TAT and tPAI-C assays; TAT normal to abnormal carryover 2.16%, abnormal to normal 0.00%,

3 | R E S U LT S

tPAI-C normal to abnormal carryover 1.4%, abnormal to normal −0.07%. Carryover testing was not performed on the TM and PIC

Ten replicate tests of high and low QC preparations tested over

assays. Unfractionated heparin added to samples at a level of 2.0 IU/

5 days gave coefficients of variation of <4.0% for both within- and

ml had no demonstrable effect on the CLEIA assays, with differences

between-run imprecision (Table 1) for all four assays. The target

of 2.07%, 0.00%, 1.30% and 0.88% for TM, TAT, PIC and tPAI-C,

values for the QC materials were assigned for the HISCL-800 only,

none of which were statistically significant.

so these values were used for both instruments. It was not always

The two instruments demonstrated excellent correlation across

possible to use the same QC lots on both instruments. Some of the

the reportable range in 230 samples tested (Figure 2). The CN-6500

mean values, particularly for TM and PIC, showed bias of up to 25%

displayed the following systemic bias (calculated from the Bland

relative to manufacturer's target values for both the CN-6500 and

Altman analysis), relative to the predicate device; TM −0.3 TU/ml,

the HISCL-800. The manufacturer's reference (RI) was verified by

TAT 0.2 mg/ml, PIC −0.009 μg/ml (0.1%) and tPAI-C −2.5 ng/ml

testing 30 samples from normal donors by all four assays on both

(Figure 3). tPAI-C showed increasing proportional bias with rising

instruments, with ≥90% of values lying within the stated RI12 with all

concentration. TAT also demonstrated a small but statistically signif-

methods, except PIC on the CN-6500 (Table 2).

icant proportional bias. Three plasmas with tPAI-C results above the

To assess linearity, doubling dilutions of four plasma samples

reportable range by both methods were excluded from the analysis.

with high levels of TM. TAT, PIC and tPAI-C, as determined by the

The CLEIA throughput was 21 tests per hour (12 samples tested

predicate method, were made manually in assay diluent. The mea-

by all 4 methods in 2 hours 15 minutes), with the first result avail-

sured concentrations were plotted against the expected, calculated

able in 17 minutes. The CLEIA throughput rate was not significantly

TA B L E 1 Between-run imprecision for low and high QC preparations HISCL-800 QC H

CN- 6500 QC H

Assay

Target

Mean

Bias

SD

%CV

Target

Mean

Bias

SD

%CV

TM (TU/ml)

91.8

113.0

23.1%

2.5

2.17%

91.8

115.0

25.3%

3.8

3.29%

TAT (ng/ml)

39.1

36.9

−5.6%

1.4

3.77%

38.1

33.6

−11.8%

0.9

2.78%

PIC (μg/ml)

7.217

7.257

0.6%

0.254

3.49%

8.007

7.160

−10.6%

0.193

2.70%

17.6

15.6

−11.4%

0.62

3.98%

17.5

17.46

−0.2%

0.50

2.85%

tPAI-C (ng/ml)

HISCL-800 QC L

CN-6500 QC L

Assay

Target

Mean

Bias

SD

%CV

Target

Mean

Bias

SD

%CV

TM (TU/ml)

22.6

27.4

21.2%

0.7

2.48%

22.6

27.7

22.6%

0.8

2.93%

TAT (ng/ml)

10.0

9.6

9.6%

0.3

3.36%

9.5

8.5

−10.5%

0.2

2.27%

PIC (μg/ml)

2.071

1.773

−14.4%

0.056

3.22%

2.071

1.620

−21.8%

0.046

2.84%

tPAI-C (ng/ml)

4.6

4.1

−10.0%

0.15

3.75%

4.7

4.6

−2.6%

0.13

2.79%

Note: 10 replications on each of 5 different days. The mean bias of measured values against the manufacturer's assigned target value for HISCL-800 are also shown.

26

Sysmex Connect – October 2021

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4

GARDINER Et Al.

Manufacturer's reference interval (HISCL-800)

HISCL-800 (n = 30)

CN- 6500 (n = 30)

TM

3.8-13.3 TU/ml

6.3-11.3

6.9-14.5

TAT

0.6-3.9ng/ml

0.40-3.12

0.40-3.25

PIC

0.24- 0.89㎍/ml

0.254-1.258

0.293-1.319

tPAI-C

3.76-14.0ng/ml

1.82-13.46

2.23-18.72

Assay

TA B L E 2 Reference interval verification in 30 samples from normal donors (2.5th–97.5th percentiles)

Note: 3, 5 and 3 samples gave values above the manufacturer's RI for TM, PIC and tPAI-C using the CN-6500. 3 samples produced a PIC value above the manufacturer's RI using the HISCL-800.

4 samples gave TAT gave values below the manufacturer's RI with both analysers. The HISCL-800 and CN-6500 produced tPAI-C values below the manufacturer's RI in 11 and 7 samples, respectively.

F I G U R E 1 Linearity for TM, TAT, PIC and tPAI-C assessed in doubling dilutions of plasma

affected by simultaneously running coagulation tests. The time

coagulation tests and CLEIA tests simultaneously, with no drop in

taken to analyse PT, APTT, Fib and D-dimer while simultaneously

throughput (CLEIA throughput 21 tests per hour). When performing

performing the four CLEIA tests on the same samples was 23 min-

coagulation tests simultaneously with CLEIA, the CLEIA throughput

utes and 30 seconds, while the time taken for PT, APTT, Fib and

is not significantly altered but coagulation test throughput is slightly

D-dimer alone was 19 minutes 35 seconds. The throughput for PT,

reduced, due to increased sampling time. The manufacturer states

APTT, Fib and D-dimer was 369 tests per hour. These times are in-

that the onboard stability of the reagents is 30 days, but that was

clusive of reflex testing for samples with high Fib and/or D-dimer

not verified during this evaluation. Although the level of imprecision

results.

obtained by repeated testing of high and low QC materials was acceptable, significant bias was observed between results obtained with both analysers and the manufacturer's assigned target values

4 | D I S CU S S I O N A N D CO N C LU S I O N S

for the HISCL-800. Specific target values for the CN-6500 were not available. We have raised our concerns regarding the QC target val-

The CN-6500 is the first routine haemostasis analyser to incorpo-

ues with the manufacturer.

rate a chemiluminescence module. At present, only TM, TAT, PIC and

Excellent linearity was obtained in a range of dilutions covering

tPAI-C assays are available on the CN-6500 but it is expected that

the reportable range. LLoD and LLoQ were within the manufacturer's

other assays will be added following this successful proof of concept.

specifications for all four assays. All were significantly lower the bot-

At present, twenty immunoassays are available on the HISCL-800

tom of the reference interval. No carryover issues were identified,

for a wide range of analytes associated with coagulation

5,14

(eg

and no interference due to heparin, lipaemia, icterus or haemolysis

PIVKA), tumour markers, virology and immunology.15,16 During this

was observed. The multiple washing processes used the CN-6500,

performance evaluation, we verified that the CN-6500 can perform

coupled with chemiluminescent detection should eliminate optical

27

F I G U R E 2 Comparability of TM, TAT, PIC and tPAI-C in 230 clinical plasma samples. The 95% CI for the slopes were TM 0.947 to 1.036, TAT 0.875 to 0.971, PIC 0.970 to 1.040 and tPAI-C 1.117 to 1.189, The 95% CI for the y-intercepts were TM −0.238 to1.131, TAT −0.381 to 1.283, PIC −0.0455 to 0.0155 and tPAI-C −0.241 to 0.598. The p value indicates the significance of the slope of the linear regression from zero. The p value indicates the significance of the slope of the linear regression from zero

Sysmex Connect – October 2021

F I G U R E 3 Bland-Altman analysis of TM, TAT, PIC and tPAI-C in 230 clinical samples. The bias and 95% limits of agreement were TM −0.3 TU/ml (−3.4 to 2.8 TU/ml), TAT 0.2 ng/ml(−5.9 to 6.4 ng/ml), PIC −0.009 µg/ml (−0.307 to 0.289 µg/ml) and tPAI-C −2.47 ng/ml (−7.34 to 2.39 ng/ml). The solid vertical lines represent the upper limit of the reference interval

28

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GARDINER Et Al.

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2020;42:387-393.

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16. Xu W, Tong Y, Li Y. Comparison of roche elecsys and sysmex HISCL immunoassays for the screening of common blood-borne pathogens. Ann Transl Med. 2019;7:300.

17. Lutsey PL, Cushman M, Steffen LM, et al. Plasma hemostatic factors and endothelial markers in four racial/ethnic groups: the MESA study. J Thromb Haemost. 2006;4:2629-2635.

interference. We felt that comparison to the predicate method was sufficient in this instance, as it has previously been shown to be unaffected by optical interference.3 The manufacturer's reference intervals were verified for TM, TAT, and tPAI-C, but we obtained a higher RI for PIC with both analysers. This may be due to the ethnicity of the normal donors (the manufacturer's RI was determined in Japanese donors).17 We would recommend establishment of a local RI in at least 120 normal healthy individuals representative of the local population prior to introducing these assays into clinical use.

The correlation between the HISCL-800 and CN-6500 was excellent in a wide range of clinical samples covering the reportable range for all four CLEIA parameters and gave results that were comparable to a previous study.5 However, the CN-6500 produced t-PAIC values with a significant bias, which indicates a problem with the calibration of this assay. However, agreement within the reference interval was acceptable (Figure 3), so the differences at higher concentrations are unlikely to be of clinical significance. Nevertheless, we have raised concerns regarding possible calibration issues with the manufacturer.

We conclude that the performance of the CLEIA assays on the CN-6500 is comparable to that of a stand-alone immunoassay analyser.

AC K N OW L E D G E M E N T S We are grateful to Dr Steve Kitchen, from the Royal Hallamshire Hospital, for providing samples for this study.

C O N FL I C T S O F I N T E R E S T This work was supported by an institutional, unrestricted research grant from Sysmex UK. CG, IJM and SJM are consultants for Sysmex Corp.

DATA AVA I L A B I L I T Y S TAT E M E N T The data that support the findings of this study are available from the corresponding author upon reasonable request.

ORCID Chris Gardiner

https://orcid.org/0000-0002-2318-0062

Hitesh Tailor

https://orcid.org/0000-0003-3615-7889

Ian J. Mackie

https://orcid.org/0000-0002-7393-2365

REFERENCES 1. Gardiner C, Lane P, Langley K, Tailor H, Machin SJ, Mackie IJ. A comparative evaluation of the CN-6000 haemostasis analyser using coagulation, amidolytic, immuno-turbidometric and light transmission aggregometry assays. Int J Lab Hematol. 2020;42:643-649.

2. Cinquanta L, Fontana DE, Bizzaro N. Chemiluminescent immunoassay technology: what does it change in autoantibody detection?

Auto- Immun highlights. 2017;8:9.

3. Chen Q, Shou W, Wu W, Wang G, Cui W. Performance evaluation of thrombomodulin, thrombin-antithrombin complex, plasminα2-antiplasmin complex, and t-PA: PAI-1 complex. J Clin Lab Anal.

2019;33:e22913.

How to cite this article: Gardiner C, Lane P, Tailor H, Machin SJ, Mackie IJ. A performance evaluation of chemiluminescence enzyme immunoassays on the Sysmex CN-6500 haemostasis analyser. Int J Lab Hematol. 2021;00: 1–6. https://doi.org/10.1111/ijlh.13656

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