towards new horizons from the land of explorers … · the sysmex european haematology symposium...

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Sysmex Journal International Vol.17 No.2 (2007) 106 When people think of Lisbon they usually think of a beautiful city at the Atlantic coast in the very West of the Iberian Peninsula, they think of castles, monasteries, Fado music and sparkling lights at night in the Old Town. From the 15 th century on Portuguese sailors embarked on expeditions to Africa, Asia and South America, driven not only by dreams of wealth and riches but also by the desire to discover new horizons. The Monument to the Discoveries in Lisbon is also symbolic for the Sysmex European Haematology Symposium 2007, devoted to the exploration of new clinical applications of new and exist- ing haematological parameters. The symposium which took place on June 13 th and 14 th , 2007, was the fourth in a row of biannual haematological symposia in different European countries: 2001 in Pfäffikon, Switzerland, 2003 in Sirmione, Italy, and 2005 in St. Wolfgang, Austria. Perhaps due to the reputation of its high quality this year's symposium could attract close to 400 visitors from 38 different countries, mostly European but also from Africa, Asia, America and the Austral-Pacific region. After the opening of the symposium by Dr. Rolf Hinzmann, Head of Medical & Scientific Affairs at Sysmex Europe, the introductory lecture was held by Dr. Michael Schaefer , President, Sysmex Europe. Dr. Schaefer asked the question "Clinical information from the IVD laboratory - end in itself or appreciated support for optimised patient management?" and made it very clear that laboratories will have to provide more direct support to patient management in the future instead of delivering "just data". Necessary is a collaborative, multi- specialty approach that puts the focus where it belongs - on the patient and the disease - breaking down depart- mental barriers that can delay diagnosis and treatment. This has become possible by using computerized patient records. Essential, however, is to guarantee adequate, respectful communication between the different special- ists and the patient since this is the only way to build up confidence. Growing confidence is actually the key term for improvement and success - try it ! The Sysmex European Haematology Symposium 2007 in Lisbon, Portugal Towards New Horizons From The Land Of Explorers Towards New Horizons From The Land Of Explorers Towards New Horizons From The Land Of Explorers Rolf Hinzmann, MD, PhD Head of Medical & Scientific Affairs Sysmex Europe GmbH, Germany [email protected] View over the Tejo River and the City of Lisbon. The Monument to the Discoveries faces West towards the Atlantic Ocean, depicting former voyagers as a symbol of the ambition to explore new horizons.

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Page 1: Towards New Horizons From The Land Of Explorers … · The Sysmex European Haematology Symposium 2007 in Lisbon, Portugal ... measurement on the Sysmex KX-21N haematological analyser"

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When people think of Lisbon they usually think of abeautiful city at the Atlantic coast in the very West of theIberian Peninsula, they think of castles, monasteries,Fado music and sparkling lights at night in the Old Town.From the 15th century on Portuguese sailors embarked onexpeditions to Africa, Asia and South America, drivennot only by dreams of wealth and riches but also by thedesire to discover new horizons. The Monument to theDiscoveries in Lisbon is also symbolic for the SysmexEuropean Haematology Symposium 2007, devoted to theexploration of new clinical applications of new and exist-ing haematological parameters.

The symposium which took place on June 13th and 14th,2007, was the fourth in a row of biannual haematologicalsymposia in different European countries: 2001 inPfäffikon, Switzerland, 2003 in Sirmione, Italy, and 2005in St. Wolfgang, Austria. Perhaps due to the reputation ofits high quality this year's symposium could attract closeto 400 visitors from 38 different countries, mostlyEuropean but also from Africa, Asia, America and the

Austral-Pacific region.

After the opening of the symposium by Dr. RolfHinzmann, Head of Medical & Scientific Affairs atSysmex Europe, the introductory lecture was held by Dr.Michael Schaefer, President, Sysmex Europe. Dr.Schaefer asked the question "Clinical information fromthe IVD laboratory - end in itself or appreciated supportfor optimised patient management?" and made it veryclear that laboratories will have to provide more directsupport to patient management in the future instead ofdelivering "just data". Necessary is a collaborative, multi-specialty approach that puts the focus where it belongs -on the patient and the disease - breaking down depart-mental barriers that can delay diagnosis and treatment.This has become possible by using computerized patientrecords. Essential, however, is to guarantee adequate,respectful communication between the different special-ists and the patient since this is the only way to build upconfidence. Growing confidence is actually the key termfor improvement and success - try it !

The Sysmex European Haematology Symposium 2007 in Lisbon, Portugal

Towards New Horizons From The Land Of ExplorersTowards New Horizons From The Land Of ExplorersTowards New Horizons From The Land Of Explorers

Rolf Hinzmann, MD, PhDHead of Medical & Scientific Affairs

Sysmex Europe GmbH, [email protected]

View over the Tejo River and the City of Lisbon.

The Monument to the Discoveries faces West towards the Atlantic Ocean, depicting formervoyagers as a symbol of the ambition to explore new horizons.

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Session 1:It's all about red blood cells: News on blood doping,fragmented red blood cells and malaria

Blood doping has been a persistent problem in endurancesports for a long time. Dr. Neil Robinson from the SwissLaboratory for Doping Analyses in Lausanne,Switzerland presented on "Fighting for fair competition -Blood doping, a persistent challenge and smartapproaches to detect it". In the light of the fact that just afew weeks before the symposium a Belgian ex-cyclingprofessional had published a book on systematic dopingin cycling and that shortly later members of the Germancycling team Telecom confessed what many had suspect-ed for long - that doping seems commonplace inendurance sports - made the lecture red-hot. Dr.Robinson described the race between professionals andscientists who develop more and more sophisticated teststo detect blood doping. The blood profiling or bloodpassport strategy that uses long-term monitoring of theathletes' haematological parameters and looks at devia-tions from the individual "normal values" is possibly thebest tool to exclude from competition all athletes withabnormal data without knowing necessarily the origin ofthe abnormality.

Diagnosis of thrombotic microangiopathies must be rapidsince they can be fatal when left untreated. The measure-ment of red cell fragments contributes to the detection ofthese conditions. Prof. Dr. Gina Zini from Rome, Italy,presented her investigations on the "Clinical usefulnessof red cell fragments identified by the Sysmex XE-2100haematological analyser". The most frequent cause oferythrocyte fragmentation is formation of thrombi in themicrovasculature in thrombotic microangiopathies suchas thrombotic thrombocytopenic purpura (TTP) orhaemolytic uraemic syndrome (HUS). Fragmentationoccurs after the passage of red blood cells through the

fibrin of microthrombi. Fragmented red blood cells areusually evaluated on peripheral blood films using opticalmicroscope observation and are estimated as a percentageafter counting 1,000 erythrocytes. The availability ofautomated haematological analysers which provide enu-meration of fragmented red cells is very useful in termsof accuracy and precision. The measurement of frag-mented red blood cells can be used for diagnosis, duringthe follow-up of patients with thrombotic microan-giopathies as well as for routine screening to promptlyidentify positive, clinically still unsuspicious cases. Themain value of the automated enumeration of fragmentedred blood cells in daily routine work resides in its highnegative predictive value.

In Europe malaria infection may go unnoticed since it isoften unsuspected in patients without a history of recenttravel to Plasmodium-infested regions. Dr. ErzsébetPintér from Budapest, Hungary, revealed the "Secret ofthe clouds - Detection of malaria infection by the SysmexXE-2100 haematology analyser" by explaining that insome cases malaria infection can cause atypical patternsin the reticulocyte and / or white blood differential chan-nel of the Sysmex XE-2100 analyser. The appearance of"pseudo-reticulocytes" with elevated fluorescence or of"pseudo-neutrophil" or "pseudo-eosinophil" cloudsshould always trigger a suspicion of the presence ofmalaria parasites although the instrument is not consid-ered sensitive enough to serve as a screening device formalaria. (For more details see Dr. Pintér's separate articlein this edition of the Sysmex Journal International.)

Session 2:It's all about leukocytes: AIDS, sepsis and radiation-induced haematological malignancies

AIDS is a global human tragedy that has its strongestimpact in the sub-Saharan countries where the number ofinfections with HIV is still on the rise. During the 3rd

South African AIDS Conference in Durban this month, itwas reported that in the 15 to 49 year age group 71 per-cent of all deaths in South Africa are due to AIDS, whilemore than 500,000 new infections occurred in 2005alone. Anti-retroviral treatment requires careful stagingand monitoring using CD4+ T cell measurements. Dr.Ilesh Jani from Maputo, Mozambique, is an expert inthis field. In his lecture "The monitoring of HIV infectionin countries with limited resources by point-of-care CD4measurement on the Sysmex KX-21N haematologicalanalyser" he presented the results of a method measuringCD4+ T cell nuclei after immunomagnetic separation on aSysmex KX-21N system. The method has been designedto provide CD4+ T cell counts and a complete bloodcount with 3-part differential leukocyte count inresource-limited settings where flow cytometry is notavailable. He concluded that in the hands of a welltrained technician, the precision of the method is compa-rable to that of a CD4+ T cell count on a conventionalflow cytometer. The KX-21N system generates absoluteCD4+ T cell counts that are in close agreement withthose yielded by a Becton Dickinson FACSCalibur forboth adult and paediatric HIV positive patients. The per-centages of CD4+ T cells generated by the KX-21N sys-

Dr. Michael Schaefer during his introductory lecture.

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tem also closely agree with those yielded by theFACSCalibur but mainly for paediatric patients. In sum-mary, this is a technology that can potentially be used insettings with a low- to medium-throughput of specimens.

Sepsis is still a severe and heavily underestimated prob-lem, having a death-toll in the industrialised countriesexceeding that of myocardial infarction. Important isearly detection of sepsis since this is a prerequisite forearly treatment. Prof. Dr. Kurt Herkner from Vienna,Austria, works on the detection of early-onset (EOS) andlate-onset (LOS) sepsis in - primarily pre-term - infants:"When time is vitally important: SIC - A novel approachfor early detection of sepsis on the Sysmex XE-2100".The aim of his ongoing study is to find a new marker forearly diagnosis of infection and sepsis by mathematicaltransformation of instrument parameters generated by theSysmex XE-2100 haematology analyser, e.g. an algo-rithm based upon the quantitative information aboutmyeloid precursor cells (IMI). The parameter is calledsingle haematological infection marker and control para-meter (SIC). In 155 sepsis episodes SIC presented withsignificantly increased values more than 24 hours earlierthan clinical signs or traditional sepsis markers such asinterleukin-8, immature to total granulocyte ratio (I/T-ratio) or IMI. For proprietary reasons details of the math-ematical calculation of SIC could not be provided at thisstage. The study is still continuing.

The next lecture was likewise focussing on sepsis: Mr.Jo Linssen, Scientific Marketing Manager, SysmexEurope, gave a presentation on "Highly fluorescent lym-phocyte count (HFLC) on the XE-5000: Can these T-cellindependent plasma cells help to differentiate betweeninfectious and non-infectious SIRS in adults?". Firstly,Mr. Linssen compared HFLC on the Sysmex XE-2100 in85 selected patients (systemic haematological diseaseswere excluded) with immunophenotyping flow cytometryon the Becton Dickinson FACSCalibur and morphologi-cal assessment of the peripheral blood film with the auto-mated microscopic blood cell recognition systemCellaVision DM96. HFLC showed an excellent correla-tion with activated B lymphocytes and no other cell lin-eage. For clinical utility he then investigated HFLCkinetics in 240 adult intensive care patients (including 68

classified as having systemic inflammatory response syn-drome (SIRS), sepsis, severe sepsis, or septic shock) and320 neonate intensive care patients (including 65 withclinical and serological signs of early-onset bacterialinfection (EOBI)). The preliminary data are promisingand demonstrate a significant increase of HFLC in sepsispatients compared to non-infectious SIRS patients.

The explosion at Chernobyl Nuclear Power Plant inUkraine on April 26, 1986, was followed by radioactivecontamination of the surrounding geographic area. Theextent of contamination by radioactive fallout and thesize of the affected population far exceed that of any pre-vious nuclear accident. Radioactive fallout drifted overparts of the Western Soviet Union, Eastern, Western andNorthern Europe, and Eastern North America. Largeareas of Ukraine, Belarus, and Russia were badly conta-minated, resulting in the evacuation and resettlement ofapproximately 300,000 people. Prof. Dr. DanyloGluzman from Kiev, Ukraine, investigated "The develop-ment of haematological malignancies in clean-up work-ers after the Chernobyl nuclear accident". In a follow-upstudy a representative sample of 246 cases withleukaemia or lymphoma was compared to an age-matched control group of 2697 individuals. Although adramatic increase in the incidence of thyroid cancer hasbeen observed among those exposed to radioactive iodinein most contaminated areas, at present a clear radiation-related increase in the risk of other forms of solidtumours has not been demonstrated. The question as towhether the incidence of leukaemia and malignant lym-phomas among Chernobyl clean-up workers is increasedis still a point of much controversy. In this comprehen-sive study increased incidence for multiple myeloma, atendency for increased non-Hodgkin's lymphoma and anincreased rate of chronic lymphatic leukaemia (CLL)were demonstrated. A peculiar feature of acute myeloicleukaemia (AML) in the clean-up workers under studywas the development of leukaemia on the background ofa preceding myelodysplastic syndrome (MDS) in 19% ofall AML cases studied. The overall incidence of AML,however, was higher in the control group. At this stagethere is no explanation for this observation.

Session 3:The Sysmex Outstanding Science Award 2007 - Theparticipants presented their results

Sysmex has embarked on spearheading the developmentof modern technology for the clinical laboratory andstrongly supports the endeavour to develop clinical appli-cations for new and existing parameters. As a logicalconsequence, Sysmex Europe has initiated the SysmexOutstanding Science Award which is focused on haema-tological cellular diagnostics involving Sysmex technolo-gies and available to all healthcare institutions. Theaward is supervised by an independent Scientific ExpertCommittee and coordinated through local Sysmex repre-sentatives. It is well financed with prizes worth 50,000altogether to honour excellent scientific work improvingcellular diagnostics in haematology and its clinical appli-cations. The first of these awards is called The RobertMartin Rowan Memorial Award in memoriam Dr. R. M.

The event took place at the superb Corinthia Hotel.

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Rowan, the former scientific advisor of Sysmex, enthusi-astic teacher, chair in many symposia and good friend tomany of us. The award was opened in 2005. Out of allapplications the Scientific Expert Committee, consistingof Prof. Dr. Giuseppe D'Onofrio, Rome, Italy, Prof. Dr.Andreas Huber, Aarau, Switzerland, Prof. Dr. SamMachin, London, United Kingdom, Prof. Dr. PranavSinha, Klagenfurt, Austria, and Prof. Dr. LotharThomas, Frankfurt, Germany, selected ten to finallycompete for three prizes. Each project received initialfunding of 1,000. In May 2007 the three winners wereselected by the committee. At the symposium eight of theten investigators presented their data:

Ms. Kim Alexander from Johannesburg, South Africa,presented her "Evaluation of the immature platelet frac-tion (IPF) in HIV/AIDS and malaria in the SouthernAfrican population". The elevated IPF levels seen inthrombocytopenic HIV patients could potentially assist inexplaining the pathophysiology which is as yet poorlyunderstood. The elevated levels seen in the patients withmalaria and thrombocytopenia possibly prove peripheralplatelet destruction.

Dr. Caroline Brusselmanns and Dr. Willy Goossensfrom Leuven, Belgium, did "A feasibility study of theCellaVision DM96 in a tertiary care hospital" to investi-gate the correctness of the instrument's pre-classificationof ca. 1.5 million randomly selected cells from pathologi-cal blood samples. They concluded: The CellaVisionDM96 is an automated cell analysis system with suffi-cient intrinsic qualities to be capable of satisfactory clas-sification of leukocytes in peripheral blood films. Theinstrument's pre-classification of cells correlates wellwith microscopy for most cell types at all leukocytecount ranges, including leukopenic samples.Repeatability of the differential is significantly betterthan microscopy for any cell type. Blood sample ageingeffects are observed after 24 hours.

Dr. Mauro Buttarello from Padova, Italy, showed in his"Evaluation of immature platelet fraction (IPF) andmean platelet volume (MPV) as risk index of vascularcomplications in patients with type 2 diabetes" that IPFand MPV were not different between controls and dia-betes type 2 patients with and without micro- ormacrovascular complications and are therefore not usefulas markers of vascular complications in these patients.

Except in the neonatal period, the presence of nucleatedred blood cells (NRBCs) in peripheral blood is alwayspathological - even if the concentration is low. The inves-tigation of the blood film has some natural limitations todetect and quantify NRBCs. The routine quantification ofNRBCs on a haematological analyser can shed more lighton the role that NRBCs play in a variety of diseases. Dr.Paolo Danise from Naples, Italy, undertook a compre-hensive "Evaluation of NRBCs in peripheral blood inhaematological diseases". He could show by analysingmore than 4,000 blood counts from 1,149 patients thatNRBCs are indeed present in peripheral blood in a highnumber of haematological diseases. This new automateddiagnostic tool forms the starting point for studies inves-

tigating the diagnostic, therapeutic and prognostic conse-quences of the presence of NRBCs.

"The immature platelet and immature red cell fraction -Novel and potent markers for targeted therapy and bonemarrow regeneration after stem cell transplantation inchildren?" asked Dr. Andreas Weimann from Berlin,Germany, in his presentation. Contrary to earlier work byothers Dr. Weimann could not derive decision criteria forplatelet transfusion after stem cell transplantation fromthe measurement of immature platelets. He stated, how-ever, that at his hospital platelet pools were transfusedfrequently and only due to clinical symptoms in allpatients and presumably often in a rather prophylacticway. Since platelet transfusion temporarily inhibitsthrombopoiesis IPF is rather useless under this condition.As a conclusion, IPF is most likely a much more clinical-ly useful and potent predictive marker in a rather strictsetting for platelet transfusions.

Session 4:The Sysmex Outstanding Science Award 2007 - Thethree happy winners !!

Ms. Marianne Schoorl from Alkmaar, The Netherlands,received the 3rd prize, worth 5,000, for her study about"Changes in platelets in morphology and RNA contentduring treatment with haemodialysis". In subjects treatedwith haemodialysis haemostatic balance is disturbed as aconsequence of extracorporeal blood circulation.Hypercoaguability is demonstrated to be strongly influ-enced by surface characteristics of the dialyser membraneand anticoagulation mode. Thrombogenicity may resultin reduced haemodialysis efficacy because the membranearea does not function appropriately. During treatmentwith haemodialysis, platelet interaction with the dialysismembrane results in activation, adhesion to the mem-brane surface, and release of platelet-derived factors. In

Ms. Marianne Schoorl is happy about the 3rd prize.

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case of platelet activation, increased amounts of degranu-lated platelets are present in the peripheral blood circula-tion. Degranulated platelets are less viable and demon-strate a shortened life span. In a longitudinal study devia-tions in platelet morphology and RNA content wereestablished in combination with analysis of markers ofplatelet activation during haemodialysis. In a group of 20patients Ms. Schoorl took blood samples at various pointsof time during haemodialysis and determined platelets,platelet distribution width (PDW), mean platelet volume(MPV) and immature platelet fraction (IPF) on theSysmex XE-2100. Blood films were microscopicallyscreened for qualitative evaluation of morphologicalaspects of platelets with a CellaVision DM96 analyzer.CD62p expression on platelets, secretion of PF4 fromalpha granules and release of serotonin from dense gran-ules in plasma are indicative for the degree of plateletactivation. CD62p expression on platelets was detectedflowcytometrically with a Beckman Coulter EPICS-XLand PF-4 and serotonin were measured with immunoas-says. Apparently healthy subjects and uraemic subjectsnot undergoing haemodialysis served as controls. Theresults are indicative of continuous platelet activationduring haemodialysis. Alterations concern decreasedmean values for platelet counts, IPF, and MPV andincreased mean values for the percentage of degranulatedplatelets. Increase of CD62p expression on platelets andrelease of PF4 and serotonin in plasma occurs simultane-ously with an increase of the percentage of degranulatedplatelets.

The 2nd prize, worth 10,000, went to Dr. CarmenCanals Suris from Barcelona, Spain, for her study"Haematopoietic stem cell mobilisation and transplanta-tion: Clinical utility of the immature reticulocyte,haematopoietic progenitor cells (HPCs) and immatureplatelet fraction (IPF) assessed by the Sysmex XE-2100haematological analyser". Several studies have shown

that HPCs correlate with CD34+ cells circulating inperipheral blood after stem cell mobilization and can beused as a guide for initiating apheresis. It has also beenreported that the immature reticulocyte fraction can beused to predict adequate harvesting of peripheral bloodprogenitor cells and serve as an early indicator of engraft-ment following haematopoietic stem cell transplantation(HSCT). Finally, some studies have suggested that thequantification of IPF can be useful in evaluating throm-bopoietic recovery after chemotherapy. Aim of the studywas to investigate the kinetics of immature reticulocytefractions, HPC, and IPF in patients mobilised for stemcell collection and during the haematological recoveryphase after autologous HSCT (ASCT). The clinical utili-ty of these parameters in timing apheresis, predictingengraftment, and optimising red blood cell and platelettransfusion after ASCT was studied. During 74 mobilisa-tion courses including 142 samples HPC showed a goodcorrelation with CD34+ cells in peripheral blood frommobilised patients. Using the two thresholds >10,000 and<3,000 HPC/mL, HPC values can successfully guideapheresis timing in 70% of the patients. For the remain-ing 30% a determination of the CD34+ cells is neededbefore taking the final decision of starting apheresis. Thestudy also suggests that the enumeration of HPC can bevery useful in evaluating the efficiency of differentchemotherapy regimens to mobilise stem cells to periph-eral blood. Reticulocyte parameters are good indicatorsof engraftment after ASCT, correlating not only with thered blood cell transfusions needed, but also with thekinetics of leukocyte and platelet recoveries. However,the absence of circulating HPCs does not preclude a suc-cessful haematological recovery. After ASCT an increasein IPF was observed in all the patients, reflecting recov-ery of thrombopoiesis after the aplastic period. Theirpotential utility to optimise the use of prophylacticplatelet transfusions needs further investigation.

Winner of the 1st prize, worth 25,000, was Prof. Dr.Florence Cymbalista from Bobigny, France, with herstudy "Usefulness of NEUT-X determination in routinediagnostic procedures: Application to myelodysplastic

Dr. Canals Suris receives the 2nd prize.

Prof. Florence Cymbalista receives congratulations for the 1st

prize from Prof. D'Onofrio, Mr. Azuma, Dr. Rolf Hinzmannand Dr. Michael Schaefer (right to left).

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syndromes". Myelodysplastic syndromes (MDS) aremalignant disorders with a poor prognosis. There havebeen recent advances in the treatment of MDS, moretreatments are available for high risk MDS, and earlydiagnosis of these forms is warranted for optimal benefitfrom treatment. MDS diagnostic features are polymor-phic and non-specific. They include anaemia in themajority of cases. All the haematological features arehighly non-specific and the standard parameters given byan automated haematology analyser rarely brings anydiagnostic argument towards the diagnosis of MDS. Theaim of this study was to investigate if certain structuralparameters which are not routinely provided by bloodanalysis with the Sysmex XE 2100 analyser could helpthe diagnosis of MDS in a simple way and be adapted toroutine practice. In this study 184 MDS cases and 3545control patients were investigated. Dr. Cymbalista suc-cessfully demonstrated that the neutrophil parameterNEUT-X (= mean value for side scatter of the neutrophilpopulation), representative of the structure of the neu-trophils, could be used for this purpose. She convertedNEUT-X into a semi-quantitative parameter, the granu-larity index GI. Negative GI in the context of anaemiaproved highly suggestive of MDS. The association of iso-lated anaemia and low GI was taken as an additional cri-terion for blood film review. Thereby, the number ofMDS that received blood film review increased from67% to 96%. This proves that this association as highlysuggestive of MDS and extremely useful to flag other-wise unrecognised MDS in routine practice. Moreover,Prof. Cymbalista confirmed that this rule was not leadingto a large excess of unnecessary blood film reviewsamong non-MDS patients as concomitantly only 2% ofcontrols were reviewed in excess. For example, isolatedanaemia in controls mostly had a GI index = 0.Therefore, Dr. Cymbalista proposes to include the GIindex in the routine parameters of the blood counts pro-vided by the Sysmex XE-2100 analyzer.

Session 5:Learn your lesson on prevalence & incidence, hardfacts about functional iron deficiency and automatedanaemia diagnostics

Do you believe in sensitivity and specificity? Perhaps

most people would be impressed by tests that can demon-strate something like 99% sensitivity and 99% specifici-ty. "These two figures alone tell you nothing" said Dr.Hans-Hermann Dubben from Hamburg, Germany, inhis interactive lecture on "Sense and crime and prophecy- Some aspects of the art and science of prediction".Prevalence and incidence are the magic words. Theydetermine the so-called positive and negative predictivevalue (PPV and NPV, respectively) which tell you thelikelihood that you are ill when your test is positive orthat you are healthy when your test is negative. PPV andNPV depend not only on sensitivity and specificity but aswell on the prevalence. A 99% specific test might befalse positive much more often than correctly positive ifthe disease measured by it is very rare. This influence ofprevalence of PPV and NPV is often neglected. Althoughintellectually understandable, our mind is often fooled bythis phenomenon when intuitive guessing is performedinstead of analytical calculation. Another intuitive misun-derstanding is that the feature a test measures and theconclusions we draw from the measurement are two dif-ferent things: A hair sample found at the site of a crimewith a DNA pattern identical to that of a suspect might -or might not, depending on the circumstances - prove thatthe hair belongs to the suspect. It does not prove that hecommitted the crime. The question how the hair got tothe site of the crime is an entirely different one. Oursuperficial belief that DNA samples can identify the gen-itor in paternity issues or the culprit of a crime simply bydemonstrating genetic identity with a sample of a suspectis entirely wrong. Likewise, diagnostic tests must be usedand interpreted intelligently. A diagnostic test shows thata marker is present or absent, elevated or decreased. Itdoes not tell why this is the case. This is left to the swiftinterpretation of the physician in the laboratory or of theclinician.

In his presentation "The red revolution - 2007" Dr. IvorCavill from Cardiff, United Kingdom, described theproblems associated with prediction of the effect of ery-thropoiesis stimulating agents (ESAs) such as erythropoi-etin and its artificial homologues. The chief factor limit-ing the effectiveness of ESAs in both renal anaemia andthe anaemia of chronic disease is functional iron defi-ciency (FID). This is most readily detected by looking atthe haemoglobin content of newly produced red bloodcells, i.e. reticulocytes. (This test is called RET-He onSysmex analysers and CHr on Bayer analysers). Therecognition of FID and the administration of intravenousiron to correct the iron supply to the marrow is the key tounlocking the full potential of ESAs. It's impossible tomake red blood cells red without an adequate iron sup-ply. It is important to recognise that erythroid iron supplyis not the same as the iron "stores". These "stores" arereally iron that has been deposited in quarantine - mainlyin the macrophages - and play no active part in iron sup-ply to developing red bloodcells. It is quite common tofind FID at the erythroid level albeit normal or raisedstorage iron levels as detected by the serum ferritin con-centration. The ability to detect decreased reticulocytehaemoglobin content gives a rational and specific basisfor the administration of intravenous iron. The optimumway to detect the failure of iron supply is to measure the

The audience is listening with passion to the discussions.

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haemoglobin content of the reticulocytes. Automated cellcounters which can do this give us the tools to do the job.Long live the revolution!

Anaemia remains as an enormous problem worldwidewith more than 2 billion people affected. Despite the highnumber of individuals living with anaemia, the impor-tance and the impact of this disease has been neglectedand the health care community has not focused onanaemia as a serious and common problem, said Dr.Sebastián Garzón from Jerez de la Frontera, Spain.Anaemia is not only a frequent condition, it also has anadverse impact on the patients' health and wellbeing andcauses a large economic burden that is difficult to calcu-late since many factors must be taken in considerationsuch as laboratory tests, drug prescriptions, hospitaladmissions, physicians' office visits, absenteeism, etc.Anaemia is often underrecognised and undertreated.Frequently it is masked by symptoms of the disease bywhich it is caused. Its very high prevalence means thatnearly all type of medical specialists must managepatients with anaemia and obviously not all of them havean equal skill and knowledge for it. In addition, there aremore and more new parameters with difficult standardis-ation and interpretation. For all that, it is common toobserve a long delay in the diagnosis and investigation ofanaemia. As a solution, Dr. Garzón presented"Automated diagnostic algorithms for the investigation ofanaemia - Towards more efficacy and efficiency in thehaematological laboratory". The process starts with acomplete blood count and the measurement of creatinineand C-reactive protein. If anaemia is detected a reticulo-cyte count and a blood film inspection will be performed.Depending on the results, parameters of iron metabolism,vitamin B12, folic acid, or haptoglobin will be deter-mined. The approach uses defined algorithms and reflextesting via the laboratory information system to screenevery patient for anaemia and to investigate the cause.

Session 6:The new Sysmex XE-5000 haematological analyser -and what comes next in laboratory medicine?

Ms. Tanja Tornow , Product Marketing ManagerHaematoloy, Sysmex Europe, presented the "Extension of

the X-Class concept - The new features of the XE-5000haematology analyser". Sysmex's new top-end analyserXE-5000 is the first haematology analyser enabling theuse of diagnostic concepts for case management and ther-apy monitoring. With its Case Manager software it assiststhe physician in the laboratory not only to report but alsoto interpret the relevant and important clinical informa-tion about the patient's condition, supporting the clinicianmost efficiently in quick diagnosis and therapy monitor-ing. Hence, new product performance specifications aswell as advanced analytical parameters with proven clini-cal utility such as immature granulocytes (IG), haemo-globin content of reticulocytes (RET-He), or humanprogenitor cell counts (HPC) are used together with theavailable patient information to help laboratory profes-sionals and clinicians in managing patients. Especiallysome of the newer extended parameters of the XE-5000like the immature platelet fraction (IPF) have proventheir clinical utility only in recent years. But their poten-tial is not always known to all users in the laboratory norto clinicians on the ward. Using the information out ofthe 76 parameters provided by the XE-5000 that is rele-vant for a particular case and helping to correctly inter-pret it is the clear aim of the new diagnostic concept ofthe Case Manager. The Case Manager is realised by atiered software concept including discrete disease andcase related information. Body fluid analysis completesthe holistic concept of the XE-5000. A dedicated bodyfluid mode capable of measuring and differentiatingblood cells of even very small numbers in body fluidscompletes the abilities of this new first-class haematol-ogy analyzer. Now a fully automated measurement tech-nique can replace a process that currently takes muchlonger by microscopy with a two-minute automatedprocess. Moreover, the classification of leukocytes inpolymorph-nucleated cells (PMN, equivalent to granulo-cytes) and mononuclear cells (MN, equivalent to lym-phocytes plus monocytes) provides additional informa-tion about the possible cause of the disease. [Editorial remark: The Case Managersoftware is cur-rently only available from Sysmex Europe and its distrib-utors.]

"Going beyond blood - Evaluation of the new body fluidmode on the Sysmex XE-5000 analyser" was the lectureprovided by Dr. Joke Boonstra from Rotterdam, TheNetherlands, who was the first to evaluate this new fea-ture of the XE-5000. Quantitative and qualitative analysisof different body fluids such as cerebrospinal fluid (CSF)and ascites is an essential tool in the diagnosis and treat-ment of patients. Microscopic analysis of body fluids istraditionally used for determination of the total leukocytecount and the leukocyte differential count. There are sev-eral disadvantages of microscopic evaluation of body flu-ids: high imprecision, high costs, a relatively long timebefore results are reported to the clinician, requirement ofskilled personnel, and finally, not everywhere are micro-scopic analyses available 24 hours a day. The obviousanswer to these problems could be automated analysis.Dr. Boonstra evaluated the body fluid mode of theSysmex XE-5000 analyzer in a prospective study usingCSF, pleural fluid, ascites, continuous ambulatory peri-toneal dialysis (CAPD) fluid, and synovial fluid. RedInspiring conversation during dinner.

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blood cell, total leukocyte, and leukocyte differentialcounts were made using a Fuchs-Rosenthal chamber andstained cytospin slides. The extended cell counting in thebody fluid mode was reflected by an improved "function-al" detection limit (= cell concentration where CV=20%)for leukocytes which improved from 50×106/L on theXE-2100 to 10×106/L on the XE-5000. In summary, thebody fluid mode on the Sysmex XE-5000 offered fastand accurate red blood cell, total leukocyte, and leuko-cyte differential counts in clinically relevant concentra-tion ranges in CSF and other body fluids. Furthermore,the exclusion of high fluorescent cells from leukocytecounting may reduce the number of manual analyses inpleural fluids and ascites.

"Where will we go from here? The near future of labora-tory medicine" is the title of the outlook to the future thatwas presented by Prof. Dr. Germano Sousa fromAmadora, Portugal. The last ten years have seenadvances in all medical sciences, with astonishingchanges in laboratory medicine in more recent years. The

advent of molecular pathology will generate opportuni-ties for professionals of laboratory medicine to contributenot only to diagnosis but to accurately predict and pre-vent disease and to participate in treatment. Genetic engi-neering and molecular biology promise a revolutionaryimprovement in medicine with already exciting advancesin heritable disease. However, of equal importance is therelationship with other physicians, scientists, healthcareorganisations, hospitals, the public, and the governments.The future of laboratory medicine will also be in eco-nomic efficiency, provision of diagnostic swiftness, reli-able service and expert consultation, and clinical support.Scientific advances will merge the roles of the laboratoryand clinical medicine. With the introduction of an enor-mous number of new tests, the clinician cannot beexpected to know what every abnormal result means orwhat reflex testing would prove helpful in diagnosis.Growing errors are resulting from his lack of knowledgethat can be avoided by the interpretation of complex lab-oratory results by knowledgeable clinical pathologists.Indeed, the application of scientific knowledge to humanhealth is a crucial aspect of laboratory medicine. Theclinical pathologists and laboratory medicine scientistsare important agents through which scientific understand-ing is expressed and they must become the bridgebetween laboratory science and medical practice.

A second day of inspiring lectures and fruitful discus-sions went by and a very much appreciated meeting cameto its end. Mr. Masahide Azuma, CEO for Europe,Middle East & Africa, Sysmex Europe, confirmed themission of Sysmex to shape the advancement of health-care and its commitment to continue to create unique andinnovative values, while building trust and confidence.Although it's over - it will go on. Sysmex Europe willshortly announce the terms and conditions for the nextSysmex Outstanding Science Award on its websitewww.sysmex-europe.com. And we hope to see you at thenext Sysmex European Haematology Symposium.

After hours: Relaxing tones from The Nana Sousa Jazz Band.