SCIENCE BOOK Europe Issue 02-2010 SUBSCRIBE Sciencebook keeps you informed of the latest diagnostics news. Sign up now and receive your copy of sciencebook at abbottsciencebook.com MISSION PAGE 2 Working directly with humanitarian partners to help address the growing health care crisis, Abbott is expanding its support for relief efforts in Haiti. EXPERIENCE PAGE 6 Find out from the Chief Techni- cian Hematology, Ms Tanja van Weel about her experiences with the CELL-DYN Emerald. Every result has a face HOPE Excellence in Transplantation Solid organ transplantation has given people with end stage organ disease and other diseases the opportunity to resume a normal life through the receipt of an organ from a donor. Once an organ is transplanted a rather complex therapeutic regimen starts to pre- vent rejection of the graft so that the transplanted organ remains functional for years within the recipient. Immunosuppression therapy is necessary to prevent destruction of the graft by the host immune system – and close monitoring of immunosuppressive drug levels is essential to ensure that transplant recipients can lead normal and productive lives. A well balanced combination of im- munosppressive drugs prevents the development of acute rejec- tion without severe side effects of immunosuppression such as increased risk for infection, malig- nancy, toxicity, and other complica- tions. Close monitoring is impor- tant to keep the balance between optimal graft function and chronic rejection. The two main drugs used in immunosuppression therapy are cyclosporine and tacrolimus, and less frequent sirolimus. These drugs are used alone or more fre- quent in conjunction with steroids and other co-therapeutic drugs such as azathioprine and MMF (MPA). Sirolimus may sometimes be used in conjunction with tac- rolimus or cyclosporine, but since tacrolimus and cyclosporine have the same mechanism of action, they are not used together. To- gether, the steroids, primary drug and co-therapeutic drug make up an immunosuppressant cocktail. Unfortunately, there are serious side effects to these medications which are nephrotoxic and result in progressive loss of renal function with the concomitant increased risk of diabetes and cardiovascular disease. Goal of the Efficacy Limit- ing Toxicity Elimination (ELITE) by Ekberg et al., 2007 – the Symphony study was to assess whether a mycophenolate mofetil (MMF)- based regimen would permit lower doses of adjunct immunosuppres- sive agents (e.g., cyclosporine, tacrolimus, and sirolimus) yet still maintain an acceptable rate of acute rejection and a more favorable tolerability profile. Un- like other studies, this trial used low dose maintenance levels of these adjunct agents from the day of transplantation. Outcome of the study: – Low dose tacrolimus therapy is an important step for- ward in reducing the nephrotoxic- ity of the drugs. Coni et al. (2008 Transplant Immunol), showed that reducing the levels of tacrolimus as low as 2 ng/mL still allows optimal immunosuppression with significant reduction in side effects. Monitoring of low levels tacrolimus is important, but the accurate and precise effects of low blood levels present a real challenge to the diagnostic laboratory. In 2009, the report of the European Consensus Conference was published by Wal- lemacq et al. in Ther Drug Monit. Their conclusion is as follows: “due to the trend to use lower tacrolimus concentrations it’s important to use a tacrolimus method display- ing a Limit of Quantitation (LOQ) around 1 ng/mL”. At the moment the ARCHITECT Tacrolimus assay is the only automated assay on market which meets this recom- mendation. Transplant whole blood immunoasay testing on ARCHITECT is designed for the complex monitor- ing of the immunosuppressant drugs. Put science on your side. Since the beginning of the 1970s, Abbott has dedicated itself intensively into diagnostic assays for infectious diseases starting with the first commercially available assay for detection of Hepatitis B surface antigen. In recent years, additional markers have been pursued, like the development of a quantitative HBsAg assay for chronic Hepatitis B therapy monitoring and HCV Core Antigen assay for easy differentiation between an active or past infection with Hepatitis C virus. These scientific advancements have been driven by a constant goal: help people live healthier lives. READ MORE PAGE 4 AD0001EU2010
Transcript
S c i e n c e b o o k E u r o p e I s s u e 0 2 - 2 0 1 0
SubScrIbE Sciencebook keeps you informed of the latest diagnostics news. Sign up now and receive your copy of sciencebook at abbottsciencebook.com
MISSIon PagE 2 Working directly with humanitarian partners to help address the growing health care crisis, Abbott is expanding its support for relief efforts in Haiti.
ExPErIEncE PagE 6 Find out from the Chief Techni-cian Hematology, Ms Tanja van Weel about her experiences with the CELL-DYN Emerald.
Every result has a face
HOPe
Excellence in TransplantationSolid organ transplantation has given people with end stage organ disease and other diseases the opportunity to resume a normal life through the receipt of an organ from a donor. Once an organ is transplanted a rather complex therapeutic regimen starts to pre- vent rejection of the graft so that the transplanted organ remains functional for years within the recipient. Immunosuppression therapy is necessary to prevent destruction of the graft by the host immune system – and close monitoring of immunosuppressive drug levels is essential to ensure that transplant recipients can lead normal and productive lives. A well balanced combination of im - munosppressive drugs prevents the development of acute rejec- tion without severe side effects of immunosuppression such as increased risk for infection, malig-
nancy, toxicity, and other complica-tions. Close monitoring is impor- tant to keep the balance between optimal graft function and chronic rejection. The two main drugs used in immunosuppression therapy are cyclosporine and tacrolimus, and less frequent sirolimus. These drugs are used alone or more fre- quent in conjunction with steroids and other co-therapeutic drugs such as azathioprine and MMF (MPA). Sirolimus may sometimes be used in conjunction with tac- rolimus or cyclosporine, but since tacrolimus and cyclosporine have the same mechanism of action, they are not used together. To- gether, the steroids, primary drug and co-therapeutic drug make up an immunosuppressant cocktail. Unfortunately, there are serious side effects to these medications which are nephrotoxic and result in progressive loss of renal function
with the concomitant increased risk of diabetes and cardiovascular disease. Goal of the Efficacy Limit- ing Toxicity Elimination (ELITE) by Ekberg et al., 2007 – the Symphony study was to assess whether a mycophenolate mofetil (MMF)-based regimen would permit lower doses of adjunct immunosuppres-sive agents (e.g., cyclosporine, tacrolimus, and sirolimus) yet still maintain an acceptable rate of acute rejection and a more favorable tolerability profile. Un- like other studies, this trial used low dose maintenance levels of these adjunct agents from the day of transplantation. Outcome of the study: – Low dose tacrolimus therapy is an important step for- ward in reducing the nephrotoxic- ity of the drugs. Coni et al. (2008 Transplant Immunol), showed that reducing the levels of tacrolimus as low as 2 ng/mL still allows
optimal immunosuppression with significant reduction in side effects. Monitoring of low levels tacrolimus is important, but the accurate and precise effects of low blood levels present a real challenge to the diagnostic laboratory. In 2009, the report of the European Consensus Conference was published by Wal- lemacq et al. in Ther Drug Monit. Their conclusion is as follows: “due to the trend to use lower tacrolimus concentrations it’s important to use a tacrolimus method display- ing a Limit of Quantitation (LOQ) around 1 ng/mL”. At the moment the ARCHITECT Tacrolimus assay is the only automated assay on market which meets this recom-mendation. Transplant whole blood immunoasay testing on ARCHITECT is designed for the complex monitor- ing of the immunosuppressant drugs.
Put science on your side.
Since the beginning of the 1970s, Abbott has dedicated itself intensively into diagnostic assays for infectious diseases starting with the first commercially available assay for detection of Hepatitis B surface antigen. In recent years, additional markers have been pursued, like the development of a quantitative HBsAg assay for chronic Hepatitis B therapy monitoring and HCV Core Antigen assay for easy differentiation between an active or past infection with Hepatitis C virus. These scientific advancements have been driven by a constant goal: help people live healthier lives. Read moRe Page 4
To Help Respond to Growing Health Crisis, Abbott Increases Aid to $2.5 Million for Haiti Relief and Recovery Efforts
background on abbott’s Existing Philanthropic Work in Haiti
Haiti relief efforts build on Abbott’s existing philanthropic partnerships to expand access to health care in the country. Since 2007, Abbott and the Abbott Fund have provided more than $34 million in grants and product donations to help address health needs in Haiti, including maternal and child health, diabetes, HIV/AIDS and malnutrition.
additional Information on abbott’s relief Efforts in Haiti
“The earthquake has had a devas-tating impact on Haiti’s limited health care system, which was already
facing significant challenges,” said Catherine V. Babington, president, the Abbott Fund. “Building on our existing partnerships with humani-tarian organizations in Haiti, we are providing funding and product donations to help address the im- mense and immediate health needs.”Initial support from the Abbott Fund for earthquake recovery efforts includes $150,000 in grants to four of Abbott’s trusted humanitarian aid partners: American Red Cross, CARE, Catholic Medical Mission Board and Partners In Health. All of these organi- zations have an established presence in Haiti, and are already mobilizing relief efforts in the country.
Abbott also is actively working with AmeriCares, Catholic Medical Mission
Board, Direct Relief International, Heart to Heart International, MAP International, Project Hope and additional organizations to identify and distribute critical nutritional and pharmaceutical products that will provide immediate relief for people affected by the earthquake in Haiti.
In addition, Abbott volunteers in the Dallas area are planning to support the efforts of the American Red Cross to respond to the disaster in Haiti. Through the American Red Cross program, “Ready When the Time Comes”, nearly 30 Abbott volunteers have received training over the past year, and are ready to assist with fundraising and other activities in Dallas to support American Red Cross relief efforts.
WeLCOMe
Innovating for the Future
Scientific discovery and innovation are the hallmarks
of Abbott’s business – and the core of our commit-
ment to advancing health and well-being. Our broad
scientific expertise enables us to create new health
care products, carry them through the critical stages
of development and then deliver them to patients
and health care providers like you around the world.
Abbott’s diverse portfolio of pharmaceuticals,
nutritionals and medical and diagnostic devices share
a common framework of excellence in science,
research, development and engineering. In 2009,
Abbott invested $ 2.7 billion in research and devel-
opment. Our ongoing investment in R&D enables us
to address the ever-changing global disease burden
and to foster new, improved solutions for emerging
health care challenges. As health care systems become
increasingly integrated, health care payers, govern-
ments, patients and others are demanding that health
care companies demonstrate clinical comparative
effectiveness, and these stakeholders increasingly
negotiate for value-based pricing. Abbott understands
these expectations and works to meet the changing
needs of our customers and stakeholders.
Regards,
Luc Ruysen
Divisional Vice President
Abbott Diagnostics Europe
Established Partnerships Lay Foundation for rapid relief; Pre- Positioned Health care Products Provide Immediate aid Following Earthquake in Haiti.
Abbott Park, Illinois — working directly with humanitarian partners to help address the growing health care crisis, Abbott is expanding its support for relief efforts in Haiti. The company will provide $ 2.5 million in grant funding and donations of
critical pharmaceutical and nutritio- nal products to humanitarian aid organizations. An initial quantity of Abbott pharmaceutical and nutritio- nal products are already in use in several locations in Haiti as a result of prior work with Direct Relief Inter- national to strategically pre-position essential health care products in preparation for potential natural disasters. These products include antibiotics, rehydration solutions and additional nutritional products
that are in critical need following the earthquake in Haiti. Abbott will continue to work with relief partners to assess and respond to ongoing needs for longerterm recovery efforts. Video of Abbott products being packed by Direct Relief Inter-national for use in Haiti is available at http://agendanyc.com/clients/abbott/preparedness.htm. Shot in mid-2009, this footage highlights ongoing efforts to pre-position aid.
about abbott FundThe Abbott Fund is a philanthropic foundation established by Abbott in 1951. The Abbott Fund’s mission is to create healthier global communi-ties by investing in creative ideas that promote science, expand access to health care and strengthen communities worldwide. For more infor-mation on the Abbott Fund, visit www.abbottfund.org.
ISBT 2010 in Berlin, GermanyThe XXXIst International Congress of the ISBT took place from June 26 to July 1, 2010 and was jointly held with the 43rd Congress of the DGTI in Berlin, Germany. Abbott Diagnostics took the opportunity to celebrate 25 years of HIV testing in the blood screening industry with an 80 m2 booth at the exhibition centre. Delegates were able to learn more about Abbott’s PRISM and ARCHITECT bloodbank solutions. Booth visitors were able to make contact with ADD scientifi c and marketing personnel and discuss product developments, view on-screen presentations or enjoy coffee in the lounge area of the booth. During the congress, Abbott Diagnostics was able to reinforce its worldwide leadership in blood screening and presented several posters to highlight recent scientifi c achievements.
Prior to the congress, Abbott Diagnostics hosted more than 125 customers in a scientific workshop on Saturday, June 26. The symposium “Advances in Viral Safety – History and Outlook” was chaired by Dr. Michael Schmidt from the German Red Cross Blood
Donor Service. His introduction was followed by a presentation by Dr. Catherine Brennan (R&D, Abbott Diagnos tics, USA) discuss-ing 25 Years of HIV Diagnostics, Historical Perspectives and Future Challenges. Finally, Prof. Richard Tedder from the Health Protection Agency, London, UK gave a fascinating update on a new retrovirus called XMRV.
The scientifi c workshop was closed by a social event where delegates could interact with speakers and Abbott was able to gather valuable feedback about future product development initiatives.
innOvaTiOn
Global Program Shows that Labs Are Vital
UniQUe
The fi rst diabetes map for smartphones
Laboratory professionals worldwide are enthusiastic about Labs Are VitalTM, an innovative program sponsored by Abbott Diagnostics in partnership with the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and professional societies around the world. Launched initially in the United States in 2006, Labs Are Vital has now spread across four continents including countries such as Brazil, United Kingdom, Ireland, and Australia.
With the clinical lab’s tremendous contribution to patient care, Labs Are Vital was designed to elevate the status of lab professionals within the health care community and the general public, address issues that face the profession, and serve as a community for laboratory professionals to ex-change ideas and get new infor-mation. Bottom line, the goal is to enhance the profession’s contribution and future.
Labs Are Vital has now grown into a multi-pronged, multi-year aware-ness program with more than 14.000 registered supporters
worldwide. The centrepiece www.LabsAreVital.com offers laboratory professionals one-stop shopping for news about the profession, downloadable tools and resources and professional meeting annou-ncements. Using social media to attract students to the profession, Labs Are Vital launched a Face-book group and a scholarship contest in the US – reaching nearly 1.8 million students interested in science. One of the European success stories of this program is the UK. Labs Are Vital has been running there since 2007, fi ve associations including the British Invitro Diagnostics Association are working together with Abbott and a communications company to promote and grow the initiative. The website www.LabsAreVital.co.uk is managed on a local level with
UK specifi c topics and information. Germany will follow in September with www.LabsAreVital.de after the offi cial announcement of the partnership with the German Association for Clinical Chemistry and Laboratory Medicine (DGKL). Labs Are Vital will have its fi rst offi cial appearance within this new cooperation end of September at the annual congress of the DGKL.
A shared booth with print materials in German language and a photo casting searching for the “Ambas-sadors for Labs Are Vital Germany” are just a few activities to mention here. With more exciting news in the works, Labs Are Vital is well on the way to setting the laboratory profession on a new course. Watch for more information coming in the next months.
“The German Society for Clinical Chemistry and Laboratory Medicine (DGKL) supports Labs are vital to draw public attention and acceptance to lab professionals and their absolutely essential – often life-saving – work.”
Dr. Jens Klabunde, Executive Director DGKL/Germany
a new diabetes care tool for I-phone
abbott just launched a really useful app to be made available to patients. “our diabetes map is an intelligent and easy-to-use tool that will help patients locate and select addresses in germany that have anything and every-thing to do with diabetes”, as Dr. Ingo Spiess, customer Development Manager with aDc, points out. With the small diabetes map, patients will be able to locate diabeto-logists, for example, or foot treatment facilities (institutions that attend to conditions of the diabetic foot), psycho-therapists or even self-help groups, and then have them-selves directly navigated there. The program that is free of charge is the fi rst of its kind on the market. “above all we want to appeal to the younger generation of diabetic patients, those who are young of heart and of course the Internet fans.” The planning of other apps is already ongoing.
The diabetes map can be found online at http://itunes.apple.com/us/app/diabetesmapp/id358721000?mt=8.
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Prof. Dr. Heiner Wedemeyer is senior physi-cian/attending physician in the department of gastroenterology, hepatology and endocrino-logy at Hannover Medical School (MHH) and Secretary General of the European Associa-tion for the Study of the Liver (EASL). Since 1996, Dr. Wedemeyer’s special area of interest has been hepatitis B, C and D viruses. He became head of a separate working group studying viral hepatitis T-cell immunology in 2001 and has been coordinator of the MHH hepatitis diagnostics lab 2004. Abbott Diagnostics since conducted an exclusive interview with Dr. Wedemeyer.
Dr. Wedemeyer, you treat a large number of patients with hepatitis b infection in your hepatitis outpatients’ department every year. How successful is hepatitis b therapy today?
Basically, we are now in a position to signifi-cantly reduce the morbidity and mortality of chronic hepatitis B for the vast majority of patients. To achieve that goal, surrogate markers need to be used during and after
treatment to check the response to therapy. Sustained seroconversion from HBsAg to anti-HBs would be ideal, but can be achieved with interferon alpha only in about five to 20 percent of cases, depending on the hepatitis B genotype. Eradication of HBsAg with HBV polymerase inhibitors is even less frequent. However, it’s very often possible to reduce virus replication to such a low level that even a highly sensitive test for HBV-DNA no longer detects virus genomes.
What are the main drugs available for treatment and what are the selection criteria?
The main treatment options currently are (pegylated) interferon alpha or specific nucleo - side or nucleotide analogs that inhibit viral replication. The type of treatment employed depends on a number of factors, e.g. patient’s age, stage of liver disease, viral load at the start of therapy and genotype. An ideal candi- date for interferon therapy for instance is a patient who is infected by genotype A, has a low viral load and about five-fold increase of
COnfidenCe
Impact of Monitoring HBsAg Levels During Therapy of HBVInfected Patients
transaminase levels. In patients matching those criteria, interferon achieves a sustained response in a shorter time than with antiviral drugs, some of which have to be given life-long. However, since interferon therapy is associated with severe side effects for patients, treatment should not be administered for longer than absolutely necessary. On the other hand, antiviral drugs with fewer side effects may cause resistance to develop.
What diagnostic markers do you use to monitor therapy, and what are the criteria for classifying treatment as successful?
The main parameter for evaluating success-ful treatment is HBV viral load. If it doesn’t decline continuously during treatment within six months, therapy needs to be modified so as to stop resistances from developing. It has been shown that non-detection of HBV-DNA in serum is no guarantee for suc- cessful elimination of hepatitis B virus. The DNA of HBV is integrated into the genome and so it can happen that viral proteins like HBsAg are synthesized, despite non-detec-tion of HBV-DNA in serum. The use of a quantitative assay for HBsAg makes it very easy to monitor long-term treatment response and may facilitate better prediction of the individual treatment duration and prognosis of long-term virologic response.
can you give examples where this diag- nostic marker was particularly useful?
The standard duration of interferon therapy is 48 weeks. If HBeAg seroconvertion occurs within this period and HBV-DNA becomes negative, treatment can be terminated. If you can additionally observe the course of HBsAg concentration and see that HBsAg was redu-
ced throughout that period but is not yet eliminated, you may continue treatment so as to achieve HBsAg elimination in the end. We observed this for instance in the case of a 49-year-old female patient who had chronic hepatitis B and C infection (see case history). We often see patients who show no reduc-tion in HBsAg concentration despite non-detectable virus load. Cases like these can point to hepatitis delta (HDV) infection.
What lies ahead for HbV treatment in your opinion, and which markers might be useful for monitoring?
Nucleotide inhibitors and combinations of various substances are attracting a lot of attention at the moment. We’re also seeing doctors make individual choices about treat- ment and treatment duration tailored to the patient’s benefit and the trend is bound to increase in future as new substances and combinations gain market approval.The goal of any treatment must be to achieve sustained response on the basis of a limited, defined treatment period. Quantitative measurement of HBsAg is essential, in particular prior to ceasing treatment after long-term therapy with HBV polymerase inhibitors, in order not to miss out on the chance of complete serologic cure (HBsAg seroconversion). I believe that the HBsAg assay should be a routine marker in long-term therapies and I would advocate testing every six months.
Finally, we recently obtained interesting data that quantitative HBsAg data may indicate if an untreated low-replicative HBsAg-positive carrier is at risk to develop clinical reactivation of hepatitis B. This paper will be published in April in the Journal of Hepatology.
case history:
• a 49-year-old female patient with chronic hepatitis b and c (genotype 2) was treated with a combination of Peg-InFα 2b and ribavirin. The patient tested negative for HbV-Dna, Hbe antigen and positive for Hbsag, anti-Hbc and anti-Hbe before starting treatment.
• Treatment duration was planned for 48 weeks.• a significant reduction in HcV-rna was evident within 12 weeks, but Hbsag
reduction was linear only.• after 48 weeks Hbsag levels were further reduced, but still slightly positive
at 0.06 Iu/mL.• Treatment was continued for another four weeks and therapeutic HbV
vaccination was also given.• 43 weeks after this treatment, the patient has shown robust Hbs sero con version
(anti-Hbs = 260 Iu/mL) and reliable HcV-rna suppression.This case demonstrates that monitoring of Hbsag concentration during treatment is a useful tool to determine optimal treatment duration. (Source: Potthoff et al., EJgH 2007)
The Virology Department of Toulouse University Hospital (CHU) is part of the Federal Institute of Biology (IFB) of Purpan consolidating activities relating to biochemistry, hematology, cellular biology, genetics, pharma-cology/toxicology, bacteriology and virology. A characteristic feature of the IFB is its shared facilities (welcome desk, general secretariat, sample center, pre-analysis division, supplies/logistics, maintenance), so that hospital activities are optimized, at the same time preserving a strong innovative potential. The Virology Department carries out its specific activities in line with medical require- ments and the teaching and research assignments of a university labora-tory. The services offered by the laboratory relate to biological exami- nations in the following areas:
• Hepatitis virus and retrovirus• Neurotropic viruses and viruses
of the immunocompromised• Respiratory and enteric viruses• Viruses of medical significance
to reproduction
The working mode of the depart-ment meant that at the outset it
could aim at a high level of services in line with a COFRAC accredita-tion subject to the standard ISO 15 189, such as was obtained in April 2007. In point of fact it can continu-ously adjust to technological evo- lution and to the overall require-ments of the various departments of CHU, Toulouse, and to the externals who place requisitions in terms of advice, analytical per - formance, time span for producing results and cost management. The laboratory is structured in three technical levels: serology, viral culture in P2 and P3 regions and molecular biology.
Historically speaking how was your lab organized before the arcHITEcT?
One important stage with the launch of AxSYM was the transition from various serological microplate tech- niques to single-tube techniques. This new concept meant that organizational improvements were possible (optimizing workplaces, polyvalence of personnel, reduction of the time span for obtaining results) and a reduced loss of reagents. The ARCHTECT helped us consolidate our organization, at the same time enabling us to run
through larger volumes.
now you have transferred the tasks previously carried out with axSYM and some of your micro- plate assays to an arcHITEcT i2000sr, what were the reasons for this choice?
There were two main criteria that dic- tated our choice of the ARCHITECT. First of all, the assay performance of the ARCHITECT range in terms of sensitivity and specificity. As a hospital lab and a reference lab, we need to equip ourselves with performing assays. Whereas sensi - tivity is a determinant factor for a virology assay, the specificity is of no less importance. In fact the number of false positive results obtained with ARCHITECT is minimal, so that as a result, the number of check-ups is reduced; consequently we have a faster speed of transmission of the results to the clinician. For our lab, the transmission time for the results to the clinician is a most important parameter. The second criteria is that of practicality, such as given by the ARCHITECT and not pro- vided by microplate-type assays. Given its principle of the one single test run and its full-scale automa-
tion, the ARCHITECT meets our requirements for productivity and our organizational objectives.Not only this, we were able to inte- grate quickly into this system of new markers like the quantitative HBs antigen, the clinical relevance of which seems interesting in the context of current antiviral regimes of treatment.
Just how is the results trans-mission time an important parameter for your lab?
We have been accredited since April 2007. One of the major indicators in the scope of this accreditation is the time span for delivering results. 90% of our results need to be transmitted within a given time. We need to provide clinicians with a maximum service in the shortest time possible. Our pre-analysis division works 24 hours a day. The tubes conti-nuously arrive in the lab and are handled as soon as possible. As a rule the results are transmitted the same day (J0), or more rarely day one (J1). This level of demand for quality in results and service does not trigger a rise in working costs. The practicality and the pace kept by the ARCHITECT system is perfectly adapted to this organization. This idea of results transmission time is vital for the qualification of donated organs or for regimes of cellular therapy. The urgency and the quality of results are of prime importance here.
What parameters do you set on the arcHITEcT?
We focus on serological testing for the viruses HAV, HBV (all markers). HCV, HIV, HTLV, CMV (including IgG avidity), Rubella.
and your top priority parameters on the arcHITEcT?
These largely relate to three clinical situations:
• Qualification of potential organ donors: serology for HIV, HBV, HCV and HTLV
• Patient report – source of accidental exposure to blood serology HIV, HBV and HCV
• Severe hepatitis report: serology for HAV, HBV and HCV
These are emergency tests carried out 24 hours a day subject to technical and biological constraints in non-working hours. In this context, the ARCHITECT is very much appre- ciated for the simplicity of its use, keeping of reagents on board and broad assay panel available, notably serology for example the availability of HTLV. The specificity of these parameters is crucial for qualifying donor organs and as an example, the new anti-HBc assay has been improved considerably.
How does your technical personnel view the arcHITEcT in your lab?
All round, they view it as an excellent instrument. It is easy to use, in fact the most user-friendly. The rate that suits our activities and the large panel are highly appreciated elements. Likewise the follow-up of quality controls independent of the manufacturer confirms the equipment’s good reproducibility.
after more than 2 years of routine with the arcHITEcT in your lab, what are your conclusions?
We can say that we benefit from better organization, most specifi-cally with the following gains:
• Reduction in result transmission times
• Optimization of resources (personnel, material) thanks to automation and the dependability of the system.
• Opportunity to develop innovative activities and to maintain constant improvement in the quality of the results produced.
feedbaCk
Integration of the ARCHITECT in a Laboratory Specializing in Virology
Part of our r&D innovation is driven by collaborations with custo-mers. We test early stage products with expert customers from the beginning. Situated around the globe, our coEs are collections of scientists, researchers and key opinion leaders who come together on a formal basis with a shared vision and purpose. a Perfect exam- ple of this collaboration is the team in university of Munich in germany, where their involvement in development of an ovarian cancer bio- maker began early on, with review and assessment of our design goals, selecting the appropriate protocols for testing the robustness of the assay, using their difficult patient samples, to testing of the final format of the assay. Their collaboration with our scientists is in- valuable at every step of the development of the assay. These centers of Excellence are the incubators for the pioneering innovations that are the future. and they make sure a robust product makes it into your hands. They are the way we will meet your needs tomorrow as we continue to Put science on your side. Learn more on abbott.com
WOrLdWide
Centers of Excellence
The virology laboratory of the Purpan hospital in Toulouse (cHu) was one of the very first hospital labs to be accredited. consequently the top priority of the laboratory is to respond to the needs of the various specialized departments of the cHu. The arcHITEcT system, at the heart of serological analysis, is adjusted to the organizational criteria called for today. Professor Jacques Izopet, Department Head, tells us about his own experience with the system.
COnfidenCe
Impact of Monitoring HBsAg Levels During Therapy of HBVInfected Patients
Since 12 years the blaricum loca- tion, in the netherlands, is an abbott Hematology customer, that started with a cELL-DYn 4000 and moved over to a cELL-DYn Sapphire two years ago. as a back-up instrument next to the cELL-DYn Sapphire, the cELL-DYn Emerald is in use for 24 hours/7 days in the laboratory of the general Hospital with in total 900 beds over two locations.
We want to find out from the chief Technician Hematology, Ms Tanja van Weel how she feels about cELL-DYn Emerald. Here is what Tanja van Weel says:
For how long are you using the cELL-DYn Emerald in your laboratory now? Since july 2009 the CELL-DYN Emerald is in use in our laboratory.
How many samples do you run on the cELL-DYn Emerald per day and how is the daily Qc proce-dure performed?On daily basis we run +/–10 pa-tients on the CELL-DYN Emerald, not that many as the CELL-DYN Emerald is used as a back-up beside our CELL-DYN Sapphire. Our Quality procedure is to run once a day a sample in triplicate and then compare the results with
our main routine analyser, the CELL-DYN Sapphire.
Which are the three features of the cELL-DYn Emerald you value most? The small sample volume allows us to run pediatric samples in duplicate if needed, first on the CELL-DYN Sapphire and then when needed on the CELL-DYN Emerald. The ease of use of the CELL-DYN Emerald makes it a perfect back-up analyser. As our technicians do not use it that often, they are still able to run sam-ples when they have not touched the CELL-DYN Emerald recently. The CELL-DYN Emerald helps us to solve the problems we see with resistant Red Cells, the CELL-DYN Emerald lyses all red cells and we can report the WBC in any case.
How long did it take to train each member of your lab staff running samples on the cELL-DYn Emerald? After half an hour training a techni-cian is capable to run a sample that is really fast.
What is the opinion of the people who work with the cELL-DYn Emerald regarding maintenance?They love it because there is no daily maintenance and only about once a month I perform
maintenance, a simple cleaning procedure. Did you know our CELL-DYN Emerald has a nick name because everybody says she’s cute, we named her “Emmy“!
can you describe the acceptance and implementation process of the cELL-DYn Emerald? We performed a reproducibility test with one sample run 20 times and a correlation with 20 samples between CELL-DYN Emerald and our CELL-DYN Sapphire. Both the reproduc-ibility and the correlation tests were in acceptable ranges.
What was your main reason to decide for cELL-DYn Emerald?Our CELL-DYN 1700 was getting old and in use for almost 13 years. We needed a suitable replacement and Abbott made a nice offer that we could accept. As we prefer to stay with the same supplier for our main analysers, Abbott was the first choice.
With the CELL-DYN Emerald in our laboratory we have an absolute certainty that we can provide results to the clinic 24 hours 7 days long, even from patients where it is a problem to get enough blood samples for CBC testing.
IntroductionModern hematology analyzers are able to process blood samples with high speed and generally good reliability. Many published evaluation studies show that for samples without obvious abnor-malities precise and accurate analytical results can be obtained with few differences between various instruments (1, 2). In such samples, the need for operator intervention is generally low, i.e. the instrument shows high first- pass efficiency. However, it appears to be more challenging analyzing samples containing cells that are not normally present in blood, like nucleated red blood cells (NRBC), immature granulocytes, and blasts (1, 3). Depending on the instrument, such abnormal cells may be posi- tively identified or their suspected presence indicated by a flag. Although these flags demonstrate reasonable performance (4, 5), different instruments show large variations in the detection of abnor- mal cells. Therefore it is mainly in the area of abnormal cell detection and flagging where differences between analyzers become evident, due to differences in technology applied. Before valid results can be reported of many abnormal blood samples in particular, operator intervention is necessary by re- peating the sample analysis, run- ning reflex tests and/or verification by microscopic examination.Tradi- tionally, analyzer evaluations have focused on analytical aspects.
Since most laboratories are nowa- days faced with pressure on their resources, it becomes increasingly important to address work process- ing efficiency as a factor when selecting new instruments for the hematology laboratory. The present report describes a recent evalua-tion study comparing a CELL-DYN Ruby with a Sysmex XT-2000i, with special regard to their operational efficiency performance.
Study designHematology analyzers: The CELL-DYN Ruby and Sysmex XT-2000i hematology analyzers are both designed for use in medium-sized laboratories. The CELL-DYN Ruby is a fully optical instrument that uses four-angle laser flow cytometry for blood cell counts including a 5-part white blood cell (WBC) differential count and reti- culocytes (6). The Sysmex XT-2000i uses a combination of impedance and optical methods and similarly generates a complete blood count (CBC) with a 5-part WBC differential count and optional reticulocytes (7, 8). Setting: The study was performed in the laboratory for Clinical Chemis- try and Hematology of the Atrium Medical Centre Parkstad in Heerlen, the Netherlands, under the direction of Dr. M. Leers. His laboratory serves a large general teaching hospital in the south of the Netherlands as well as general practitioners in the region. The laboratory routinely uses the Sysmex XE-2100 hematology analyzer with a Sysmex XT-2000i
as a backup instrument.Samples: During a period of one month the laboratory analyzed a total of 313 samples that were randomly taken from the daily workload. Analyses using the CELL-DYN Ruby and Sysmex XT-2000i were performed on residual blood samples within
6 hours from the time of blood collec- tion, after all requested assays had been completed. Blood samples were anticoagulated with K2-EDTA. Once chosen for the evaluation study, the identification was removed from the sample, guaranteeing anonymous processing. All samples were run in CBC mode and 100
samples with supplementary reticu- locyte analysis. Both instruments were calibrated according to manu- facturers’ recommendations, and quality control was performed twice daily at three levels. Com- mercial blood-derived material was used for calibration and quality control. Blood smears were
exPerienCe
Small and Powerful
TeCHnOLOgy
Comparative efficiency study of CELL-DYN Ruby and Sysmex XT-2000i
Table 1: criteria for analyser rerun and smear review
analyser analyser reflex and rerun criteriaa Smear review criteriab
abbott cELL-DYn ruby • Presence of FWBC flag in CBC mode Reflex to CELL-DYN Ruby NOC mode
• Presence of RRBC flag in CBC mode Reflex to CELL-DYN Ruby RRBC mode
• WBC >250 x 109/L Dilute and rerun in CELL-DYN Ruby CBC mode
• PLT >2000 x 109/L Dilute and rerun in CELL-DYN Ruby CBC mode
• MCHC >38 g/dL Incubate in 37°C waterbath and rerun in CELL-DYN Ruby CBC mode
Suspected Wbc/nrbc abnormalities• Samples with one or more of the following flags; NRBC,
FWBC, RRBC, and BLAST• Samples with an IG or IG/BAND flag and a neutrophil
count of >0.5 x 109/L• Samples with a VarLym or VarL/BLAST flag and a
lymphocyte count of >3.0 x 109/L• Samples with a BAND flag and a neutrophil count of
>6.5 x 109/L
Suspected platelet abnormalities/aggregates• Samples with URI flag and a platelet count of <50 x 109/L• Samples with severe thrombocytopenia (<50 x 109/L)
in the absence of neutropenia (WBC > 2.5 x 109/L)• Samples with a NWBC flag
Sysmex xT-2000i • WBC >300 x 109/L Dilute and rerun in XT-2000i CBC mode
• PLT >2000 x 109/L Dilute and rerun in XT-2000i CBC mode
• PLT <50 x 109/L Reflex to XT-2000i CBC+RET mode to obtain optical platelet count
• MCHC >38 g/dL Incubate in 37°C waterbath and rerun in XT-2000i CBC mode
• NRBC or RBC Lyse Resistance Flags Reflex to Sysmex XE-2100 analyser
Suspected Wbc/nrbc abnormalities• Samples with any WBC/NRBC related flag• Samples with WBC differential (partially) suppressed• Samples with isolated severe neutropenia
(<0.5 x 109/L) in the absence of thrombocytopenia (PLT > 150 x 109/L)
Suspected platelet abnormalities/aggregates• Samples with PLT Clumps? Or PLT Clump(s) flags
when platelet count is <150 x 109/L• Samples with PLT Abn Distribution flag when platelet
count is <150 x 109/L • Samples with isolated thrombocytopenia (<150 x 109/L)
in the absence of neutropenia (WBC > 2.5 x 109/L)
a CELL-DYN Ruby reflex processes and film review criteria defined by the Operators Manual and the Abbott Diagnostics study coordinator. Sysmex XT-2000i reflex/review criteria adopted from the laboratory’s Standard Operating Procedures (SOP). For CELL-DYN Ruby NOC and RRBC correspond to ‘Nucleated Optical Count’ and ‘Resistant RBC’ modes respectively. b Smear review criteria applicable to nucleated cell (WBC/NRBC) and platelet components only. Review criteria defined for detection of red cell abnormalities were not applied in this study. Flag abbreviations: NWBC (Non-White Blood Cell), NRBC (Nucleated Red Blood Cell), FWBC (Fragile White Blood Cell), RRBC (Resistant Red Blood Cell), IG (Immature Granulocyte), BLAST (Immature blast cell), and URI (platelet Upper Region Interference).
At May 10 – 12th the International Society of Laboratory Hematology symposium was held in Brighton in the United Kingdom. The ISLH is a global symposium for Laboratory Hema- tology with the emphasism on daily/routine testing performed at the Clinical Hematology laboratory and is in its sort the only global scientific event. Nearly 750 people attended the meeting where Abbott Hematology was present with a booth; a busy meeting point during the event for many CELL-DYN users and interested customers to find out the latest news and updates in Abbott Hematology.
Customer feedback was gained for the Sapphire V3 software with its new extended Optical RBC parameters and also the first HSQ project Advisory group meeting was held at the ISLH.
The HSQ project is Abbott’s new Hematol-ogy platform that is currently in feasibility state and expected to go on market when ready in 2013. During this Advisory group meeting key-opinion leaders in Hematology were informed on the status of this project, followed by an open and interactive discus- sion. Close relationship with and willingness to listen to the Voice of the Customer are examples of what Abbott Hematology is undertaking to develop the right products on the market.
At the Abbott booth the CELL-DYN Emerald, CELL-DYN Ruby and the Pathfinder 350S were demonstrated. Video demonstrations showed the potential of AbbottLink and AMS Hematology, Abbott’s European Middle-
ware solution. The Pathfinder 350S is a benchtop sorting device that runs at 350 tubes per hour, in combination with CELL-DYN instruments and AMS Hematology Middleware, the PF350S is Abbott’s answer, so called High Efficiency Hematology pro- gram, to automation where tracks are too expensive, not needed and showing to be not economical.
The High Efficiency Hematology (HEH) solution will allow Abbott Hematology to step into mid-high volume hematology laborato-ries and compete with track automation. The high First Pass Efficiency from CELL-DYN instruments will in most cases reduce the need for reruns, reflex or manual smears signifi-cantly, and minimize the need to move sample tubes by a track. A LeanPathway workflow analysis will help to identify how operational efficiency can be optimized and transform to a High Efficiency Hematology laboratory.
At May 11th an Abbott Luncheon was organised with approximately 125 people listening to scientific topics while enjoying their lunch. The Luncheon showed Abbott’s dedication to Hematology, good speakers on the program and again like last year in Las Vegas Abbott’s luncheon was the best visited sponsor session. Giacommo Vacca (Abbott Santa Clara) presented Laser Raster- ing, Abbott’s promising new technology for the next generation of Hematology analysers.First basic data from the Laser rastering showed excellent correlation with the MAPSS technology, still MAPSS is considered to be best in class technology in routine hematol-
ogy todays. Prof W.W. van Solinge (UMC Utrecht, NL) presented the clinical utility of the new xRBC parameters of the CELL-DYN Sapphire available in the new V3 software. With these new extended parameters Abbott Hematology did fulfil a long lasting promise to their Hematology portfolio. Dr J. Cid (Hosp de Tarragona, Spain) expressed the need and use of CD61 platelet counting at patients undergoing platelet transfusions.CD61 an immunological marker for counting platelets is available on the CELL-DYN Sapphire allowing laboratories to report the correct Platelet results within 4 minutes, especially needed in difficult samples/cases where
patients are in critical condition and the platelet result will determine whether a transfusion is needed yes or no. Having the possibility to run CD61 on the Sapphire shows the technology leadership of Abbott in Hematology, as no competitor can run monoclonal markers like CD61 on their instrument routinely. Overall Abbott’s presence with booth and Luncheon confirmed that Abbott is being recognised as an important, innovative player in Hematology, building the future based on the Voice of the customer with a high-end technology called Laser Rastering to become a Leader in Hematology!
aCTive
ISLH 2010 in Brighton, UK
prepared and stained of all samples, irrespective of the results from the analyzers. A second part of the original study comprised samples that were selected because they contained specific abnormalities; these samples are not included in the present report.Data analysis: The results of the initial sample analysis on both analyzers were reviewed using the criteria shown in Table 1. For each sample it was thus decided if further action was necessary, repeated sample processing by the analyzer (reflex and rerun) or microscopic examination (smear review) or both. The numbers of samples in each of these process-ing pathways were counted.
resultsThe present report only includes the operational efficiency analysis of the subset of unselected samples. The analytical and efficiency com- parison of the two analyzers, using all samples enrolled in the study, is the subject of a full report elsewhere (9). As Figure 1 shows, there were six out the 313 samples (1.9%) run on the CELL-DYN Ruby that needed a reflex test: four in NOC mode due to a FWBC (fragile WBC) flag and two in RRBC (resistant RBC) mode because of the possible presence of lyse-resistant RBC. Five of these six samples also needed smear review according to the criteria applied (Table 1). In addition to the reflex tests, there were 17 samples that required smear review for various reasons. In total, 22 smear reviews were performed: 20 for
suspected WBC or NRBC abnor-malities and two for platelet-asso- ciated reasons. The total smear review rate was 7.0%. Eventually, 28 additional operator interventions were required before the results could be reported (Figure 1). When the samples were run on the Sysmex XT-2000i, 18 (5.8%) needed a reflex or rerun: 12 required a reflex optical PLT analysis in reticulocyte mode and one had to be rerun after dilution due to exceeding the upper limit of linearity of the WBC count. The remaining five had to be referred to an alternative analyzer since the Sysmex XT-2000i does not have the capability for measuring samples with NRBC (n=4) and lyse-resistant RBC (n=1). Apart from reflex and rerun, all these 18 samples also needed smear review. Another 13 samples required smear review, bringing the total smear reviews to 31 (9.9%): 24 for suspected WBC abnormalities and seven due to platelet flags. Processing the 313 samples with the Sysmex XT-2000i yielded a total of 49 additional operator interventions (Figure 1).
Discussion and conclusionsIt is only in some recent publica-tions that operational efficiency of hematology analyzers is addressed as an issue of interest (10). Many laboratory professionals realize that it is essential to reduce manual (second-pass) interventions when- ever possible in order to cope with the continuing pressure on labora- tory resources. Because the need for second-pass processes
(additional reflex tests, analyzer reruns and microscopic smear reviews) may differ between ana- lyzers, the subject of operational efficiency should become an inte- gral component of comparative evaluation studies. In the present study we have shown that there are considerable differences in operational efficiency between two analyzers that are analytically rather similar (9). Processing the samples with the CELL-DYN Ruby required a total of 28 operator interventions (8.9%), whereas the Sysmex XT-2000i needed significantly more, namely 49 interventions (15.7%; p < 0.014). Important to realize is the fact that the samples in this study were randomly taken out of the daily workload without any prior selection and thus form a good representa-tion of the patient population handled by the laboratory of Atrium Medical Center Parkstad. This patient popu- lation mainly consists of in-patients and out-patients of a general hospi- tal as well as a smaller number of patients sent by general practition-ers. In other laboratories the patient mix can be different and this may reflect in different intervention rates. In addition, the local criteria for rerun and smear review may also differ between laboratories, which will also have an effect on the rerun and review rates. On the other hand, since the difference is largely influ- enced by the technology used in the respective analyzers, we con- sider it likely that the general finding in this study (CELL-DYN Ruby more efficient than Sysmex XT-2000i) can be similar in other laboratories.
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2008;130:104 – 16. 2. Kang S-H, Kim HK, Ham CK, Lee DS, Cho HI. Comparison of four hematology analyzers,
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4. Buttarello M, Bulian P, Temporin V, Rizzotti P. Sysmex SE-9000 hematology analyzer: Performance evaluation on leukocyte differential counts using an NCCLS H20-A protocol. Amer J Clin Pathol 1997;108:674 – 86.
5. Müller R, Mellors I, Johannessen B, Aarsand AK, Kiefer P, Hardy J, et al. European multi-center evaluation of the Abbott Cell-Dyn Sapphire hematology analyzer. Lab Hematol 2006;12:15 – 31.
6. Lehto T, Hedberg P. Performance evaluation of Abbott CELL-DYN Ruby for routine use. Int J Lab Hematol 2008;30:400 – 7.
7. Fernandes B, Hamaguchi Y. Performance characteristics of the Sysmex XT-2000i hematology analyzer. Lab Hematol 2003;9:189 – 97.
8. Langford K, Luchtman JL, Miller R, Walck D. Performance evaluation of the Sysmex XT-2000i automated hematology analyzer. Lab Hematol 2003;9:29 – 37.
9. Leers MPG, Goertz H, Feller A, Hoffmann JJML. Performance evaluation of the Abbott CELL-DYN Ruby and the Sysmex XT-2000i haematology analysers. Int J Lab Hematol 2010;32:in press.
10. Böer K, Deufel T. Workflow restrictions on hematology analyzers XE-2100 and XS-800 when assaying pediatric samples with limite volume. Clin Chem Lab Med 2009; 47:607 – 11.
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