Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\n
Throughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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\r\n\tThe purpose of this book is to analyze state of the art and the most interesting lines of research in the field of forensic medicine, laying the foundations for exploring new perspectives of great interest to the scientific community in multiple disciplinary sectors. The following disciplinary topics will be addressed: Forensic Pathology, Forensic Anthropology, Forensic Toxicology, Legal Medicine, Forensic Genetics, and Bioethics. Therefore, the book project aims to collect several themes, sometimes connected to each other, in order to create a practical tool of knowledge usable both by the experts of the discipline and by young and emerging researchers.
\r\n
\r\n\tForensic medicine is a scientific discipline characterized by continuous evolution due not only to progress in medical knowledge but also to changing juridical and social requirements. Given the nature of the discipline, this book, through a multidisciplinary approach, aims to offer the reader the best evidence and the most up-to-date reflections in the fields of Forensic Pathology, Forensic Anthropology, Forensic Toxicology, Healthcare Risk Management, Forensic Genetics, and Bioethics. In addition, it is intended to offer the reader an insight into the future of the discipline, which in some cases is already the present. Thanks to the latest developments in the digitization of healthcare, such as artificial intelligence, virtual reality, and robotics, the future of forensic science may change radically. Knowing how technological advances may affect this scientific discipline, its criticalities, and potential will enable those who practice it to lead change while always pursuing the protection of the human being.
",isbn:"978-1-83768-045-0",printIsbn:"978-1-83768-044-3",pdfIsbn:"978-1-83768-046-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"b0514220e40dc2f90b1dcd0445248b72",bookSignature:"Ph.D. Roberto Scendoni and Dr. Francesco De Micco",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11706.jpg",keywords:"Forensic Pathology, Histopathology, Forensic Radiology, Forensic Anthropology, Forensic Toxicology, Clinical Risk Management, Patient Safety, Medical Liability, DNA Profiling, Forensic DNA Extraction, Parentage Testing, Bioethics",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 12th 2022",dateEndSecondStepPublish:"June 9th 2022",dateEndThirdStepPublish:"August 8th 2022",dateEndFourthStepPublish:"October 27th 2022",dateEndFifthStepPublish:"December 26th 2022",remainingDaysToSecondStep:"17 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Researcher in forensic pathology and anthropology, member of the AgEstimation Project at UNIMC and the American Academy of Forensic Sciences - Anthropology section.",coeditorOneBiosketch:"Research Fellow in Health Care Risk Management, Bioethics, and Forensic Anthropology. Dr. De Micco is also a Clinical Risk Manager, Member of the Clinical Bioethics Service, and Member of the Claims Assessment Committee at Campus Bio-Medico University Hospital, Italy.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"333983",title:"Ph.D.",name:"Roberto",middleName:null,surname:"Scendoni",slug:"roberto-scendoni",fullName:"Roberto Scendoni",profilePictureURL:"https://mts.intechopen.com/storage/users/333983/images/system/333983.jpg",biography:"Roberto Scendoni is a Research, Teaching Assistant and Exam Committee Member in Legal Medicine, Toxicology and Social Medicine - at the University of Macerata, Italy. In 2022 he received the national scientific qualification as Associate Professor in the Italian higher education system, in the field of forensic and occupational medicine. He conducts research activities in forensic medicine, forensic anthropology, forensic toxicology, risk management. He is consultant for forensic autopsies and external examinations, personal injuries, attempted murders, personal identification, malpractice. He is the authored/co-authored of 33 Journal Papers, 6 Book Chapters and 13 publications (abstracts, reports, conference proceedings etc.). He has been involved in many national and international training events as speaker.",institutionString:"University of Macerata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Macerata",institutionURL:null,country:{name:"Italy"}}}],coeditorOne:{id:"471220",title:"Dr.",name:"Francesco",middleName:null,surname:"De Micco",slug:"francesco-de-micco",fullName:"Francesco De Micco",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003SZ7x8QAD/Profile_Picture_2022-04-29T13:46:32.jpg",biography:"Francesco De Micco is a Research Fellow in Legal Medicine at Campus Bio-Medico University, Italy. He is the Clinical Risk Manager, of the Campus Bio-Medico University Hospital Foundation. In the same institution, he is the Member of the Clinical Bioethics Service and Member of the Claims Assessment Committee. 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\n
1. Introduction
\n
Evacuated blood-collection tubes are evacuated containers intended for a venous blood specimen collection. They consist of a tube and a closure, which has to be tight to restrain low pressure—vacuum inside the tubes during their shelf life—but, on the other hand, it also has to be soft enough to let a sharp end of a blood-collection device to penetrate into a tube. The collection device has a disposable needle attached to the other side for phlebotomy.
\n
Evacuated blood-collection tubes improved patients’ and medical personnel’s safety and mostly replaced classical tubes, which required a syringe and a needle for a specimen collection. In a continuation, wherever a tube is mentioned, the evacuated blood-collection tube is meant.
\n
To prevent blood coagulation, tubes contain anticoagulants, either as dry substances attached to the internal walls or as solutions. Widely known and used are sodium citrate and salts of ethylenediaminetetraacetic acid (EDTA), usually present either as dipotassium or tripotassium salts, K2EDTA or K3EDTA.
\n
Other substances, additives might be introduced as well to ensure the adequate properties or behavior of the tubes’ internal walls or closures; nevertheless, they are expected not to interfere with a determination and affect analytical results. A noncompliant constituent detected in citrate tubes was magnesium which leached from a stopper and was consequently influencing the prothrombin time (PT) results [1]. A comprehensive study evaluating different tubes comprising also recently introduced low-magnesium version confirmed that the PT and INR differences between the tubes are correlated with the magnesium concentration differences [2].
\n
Manufacturers are obliged to specify on the label of a tube: a type of anticoagulant, a nominal draw volume, a lot number, and expiration date; within this text, we use a term expiry date as well.
\n
Anticoagulant concentration in a blood sample after specimen collection should be within an appropriate range; otherwise, analytical results might be altered. To reach this objective, an accurate amount of anticoagulant should be introduced into a tube during production, and a draw at the moment of a specimen collection should be adequate to ensure a volume of blood entering a tube is within an acceptable range. A label on a tube provides guidance for inspection if the volume is within the suggested limits; however, this is only true if the label is precisely and accurately positioned.
\n
The latest version of the GP39-A6 standard of the CLSI standardization body (Clinical and Laboratory Standards Institute) [3] requires of the tubes’ manufacturers to ensure that until expiration date, the anticoagulant concentration remains within the 5% range of the value stated on a label. A draw volume is considered acceptable if it does not differ from the stated nominal volume for more than ±10%.
\n
The standard GP34-A recognizes the importance of appropriate blood-to-EDTA ratio for obtaining optimal examination results but avoids stating the exact limits. The EDTA can, if in a concentration which is too high hypertonically shrink red cells, affect red cell size and cause morphological changes. On the other hand, it can too extensively chelate calcium and other cations such as magnesium and zinc and affect the activity of alkaline phosphatase enzyme label used in chemiluminescent assays or reduce the efficiency of the recognition of proteins by antibodies due to the proteins’ conformation changes [4].
\n
The predecessor of CLSI, the National Committee for Clinical Laboratory Standards (NCLLS), was in the H1-A5 standard more explicit in terms of some anticoagulants’ concentrations [5]. It explains that only a little bit less than a half (1.15 mmol/L) out of the total calcium concentration (2.5 mmol/L) corresponds to unbound calcium that needs to be chelated stoichiometrically with EDTA to prevent coagulation. For that reason, it suggests that EDTA concentration in blood should be between 3.7 and 5.4 mmol/L, since excessive concentration causes morphological changes in the blood.
\n
Not consistent with this requirement was DIN ISO 6710: 1996-12 standard requiring the EDTA concentration within the 4.11–6.843 mmol/L range [6].
\n
A potential user can during time come across the tubes which were produced by not having the same set of requirements on the mind. As we already previously demonstrated, the tubes if evaluated as such not yet in contact with a blood sample are not all the same, and change in their own characteristics during their shelf life and the testing procedure which we suggested are easy to perform [7].
\n
A concise review reflects on the behavior of EDTA as an anticoagulant in hematology and furthermore discusses its usage in proteomics, general clinical chemistry, and its applicability for measuring cytokines, protein, peptides, and cardiac markers [8]. Elsewhere, influences of a form of EDTA and its concentration on the results of hematological tests were profoundly discussed in relation to spurious counts and results regarding platelets [9], white blood cells, red blood cells, hemoglobin, red cell indices, and reticulocytes [10]; under-filled or over-filled evacuated tubes changing the anticoagulant level in a sample are exposed as an influential pre-analytical source of errors.
\n
For citrate tubes the DIN ISO 6710: 1996-12 standard recommends trisodium citrate solutions with concentrations between 100 and 136 mmol/L; however, the H1-A5 standard specifies the concentrations 105, 109, and 129 mmol/L.
\n
Due to all these differences, the GP39-A6 standard omitted all the anticoagulant concentrations’ details, leaving it entirely to a producer to bear the responsibility for securing appropriate concentration, fulfilling all the requirements, and demonstrating that they are actually met, or in other words verifying that the tubes are actually fit for purpose.
\n
The GP34-A standard provides guidance for validation and verification of tubes for venous and capillary blood specimen collection [4]. Both a manufacturer and a clinical laboratory are required to perform a comparability study on blood samples for two or more sets of tubes comprising a set which was already evaluated and approved previously. A manufacturer performs such a test after a new product was developed or where any correction actions are necessary for the production process. The laboratory needs to do it when switching from one product to another or when changing a vendor.
\n
A within-tube precision study requires a minimum of 20 subjects, and each sample needs to be analyzed in replicates; an appropriate number of samples, evenly distributed through the analytical measurement, are essential for trueness evaluation [4]. Several studies with sometimes dissimilar outcomes can be found in the literature.
\n
Two blood-collection devices either with an aligned [Becton Dickinson (BD)] or at an angle needle holder (Greiner Labortechnik GmbH) were evaluated either enabling a direct linear (BD) or interrupted nonlinear blood flow. A mechanical strain on blood cells was recognized as a factor potentially causing the efflux of intracellular constituents into the serum in an interrupted nonlinear flow. The magnesium, plasma hemoglobin, and prothrombin time within-subject variations were confirmed in 55 healthy individuals using a Student paired t-test. A difference in a tube material either glass or polymer was also recognized as a likely contributing factor [11].
\n
Nevertheless, contrasting outcomes were obtained for prothrombin time determinations in the glass and PVC tubes with two distinct citrate concentrations where neither material caused the significantly different results [12]. Yet another study, establishing a protocol for comparing the citrate evacuation blood-collection tubes with glass tubes employing eight measuring systems, confirmed a statistically significant but clinically not relevant difference in prothrombin time results, which were more pronounced with the tubes of the lowest 2.7 mL draw volume [13].
\n
Differences in some parameters were confirmed if BD plastic citrate tubes were used instead of glass tubes, but they were considered unlikely to be clinically significant [14], though a comprehensiveness of a study was challenged arguing that only healthy volunteers were involved and by these means it was not yet proven that glass tubes are interchangeable with the plastic tubes [15]. But a study performed on Greiner glass citrate and plastic tubes confirmed that the tubes are substitutable as far as either untreated or patients on a traditional oral anticoagulant therapy are concerned and that this applies for the whole shelf life of the tubes [16].
\n
Nevertheless, the plastic tubes of different brands evaluated on patients and healthy volunteers were confirmed to be statistically but not clinically significantly different [17]. For patients on oral anticoagulant therapy with vitamin K antagonists, ANOVA test confirmed statistically significant differences in prothrombin time for the tubes of four different types [18]. The study supports the claim that validation is always necessary when there is a change in a tube type.
\n
A research performed on a group of individuals evaluating the effect of under-filled EDTA tubes on hematological parameters by employing a particular type of analyzer [19] leads to contrasting outcomes not necessarily aligned with other studies [20] and general principles and recommendations.
\n
Validations and verifications as required by the standard GP34-A are complex to perform, time demanding, and require resourceful personnel [4].
\n
The standard exposes a blood collection as a pre-analytical (preexamination) source causing varying degrees of errors. It brings to light a lack of a mechanism that would enable systematic evaluations of the influences of pre-analytical (preexamination) variables on laboratory test (examination) results [4].
\n
The characteristics of the tubes entering the pre-analytical phase are such variables, and this is where this chapter tends to contribute.
\n
Differences between tubes of different brands examined 5 years apart in time are going to be enlightened, and the testing procedures which are fast, cheap, and easy to implement into laboratory practice are explained in full details. Robustness of personal profiles of athletes and validation studies performed on blood samples can profit from knowing the attributes of the tubes that were actually used or evaluated.
\n
\n
\n
2. Quality of evacuated blood-collection tubes for hematological tests reevaluated in 5 years’ time
\n
In this section, we compare the results of a quality evaluation of the blood-collection tubes, on which we previously reported [7], with the results obtained in 5 years’ time. The same producers were considered, namely, Becton Dickinson, Greiner Bio-One, and Laboratorijska tehnika Burnik d. o. o.
\n
\n\nFigures 1\n–\n4\n are dedicated to the tubes of four different brands. The abscise axis stands for a draw volume. Ordinate on the right indicates an anticoagulant concentration expected for a blood sample after a specimen collection. We are going to explain the meaning of the left ordinate axis, which relates to a testing procedure, later. A frame in green indicates the limits set by the H1-A5 standard [5]. The horizontal lines confine the range of the acceptable anticoagulant concentration; the left vertical line represents a limit under which a draw volume is expected not to fall to prevent the anticoagulant concentration to rising too high.
\n
Figure 1.
Anticoagulant concentrations and draw volumes of the A brand tubes obtained 5 years apart in time (orange/blue) and of the tubes F not previously included (the numbers in the labels indicate time until the expiration).
\n
Figure 2.
Anticoagulant concentrations and draw volumes of the B brand tubes obtained 5 years apart in time (orange/blue); the numbers in the labels indicate the time until the expiration.
\n
Figure 3.
Anticoagulant concentrations and draw volumes of the C brand tubes obtained 5 years apart in time (orange/blue); the numbers in the labels indicate the time until the expiration.
\n
Figure 4.
Anticoagulant concentrations and draw volumes of the D brand tubes obtained 5 years apart in time (orange/blue); the numbers in the labels indicate the time until the expiration.
\n
We kept the assigned marks A, B, and C from the previous study for the K3EDTA tubes, and D for the K2EDTA tubes, not disclosing the producers’ identity. We additionally included the tubes F, not previously evaluated. The more recent results are marked with an asterisk; a number indicates the number of days until the expiration.
\n
Ellipses in \nFigures 1\n–\n4\n provide an insight into a spread of results obtained for the tubes within a series of measurements. Ellipses in blue correspond to the more recent results; those in orange originate from a previous study. A length of a horizontal axis of an ellipse equals a standard deviation of the draw-volume measurements; a vertical axis indicates a standard deviation of the anticoagulant concentration as expected for blood samples. A crossing of the two axes of an ellipse is defined by the mean values of the two parameters. The smaller the ellipse, the higher the quality of the produced tubes in terms of their precision or, in other words, a repeatability of a product.
\n
\n
2.1 K3EDTA tubes
\n
From this point of view, the A brand tubes were and remain of a high quality. In spite of having a very long expiration date, unless very close to the expiration (A*18), the draw volumes generally remain adequate; however, the anticoagulant concentration is too high and not in the accordance with the higher limit set by the H1-A5 standard [5]. All the ellipses of the A brand tubes are above the green rectangle in \nFigure 1\n. The same is true for the tubes F, which are of the same manufacturer. This example demonstrates that an adequate draw volume does not yet ensure the adequate anticoagulant concentration as far as the H1-A5 is concerned. The tubes were obviously produced following an older DIN ISO 6710: 1996-12 standard, for which the anticoagulant concentration 6.843 mmol/L was still acceptable. With this limit in mind, only the A*18A anticoagulant concentration would be excessive. The characteristics of these tubes clearly contrast those of the tubes B and C, as the figures in the continuation demonstrate.
\n
In the B brand tubes (\nFigure 2\n), an improvement in the overall quality of the results is evident in 5 years’ time. Previously the ellipses were much larger, and they exceeded the upper anticoagulant concentration limit even with the draw volumes very close to the nominal 3 mL mark. The ellipses in blue are small and remain within the green rectangle during the whole shelf life; nevertheless it has to be mentioned the shelf life was at the time of purchase much shorter than in the A brand tubes.
\n
The C brand tubes exhibit a good repeatability of the product; however, the anticoagulant concentration starts exceeding slightly the higher-anticoagulant concentration limit already with the draw volumes approaching 2.8 mL, proving that the draw volume within the acceptable range does not yet guarantee the correct anticoagulant concentration.
\n
\n
\n
2.2 K2EDTA tubes
\n
The product repeatability of the D brand tubes is good, but the anticoagulant concentration starts exceeding the upper limit already approximately 200 days before the expiration date and with the draw volumes falling below 2.9 mL what is far above the acceptable lower limit.
\n
This study confirmed that a control of a draw volume is not the main quality issue and does not ensure that the anticoagulant concentration is adequate. Only in four cases, the draw volumes below the 2.7 mL limit were observed, and this only happened when the tubes were tested closer than 20 days before their expiration date. On the other hand, in more than 20 cases, the anticoagulant concentration limit as set by the H1-A5 standard was exceeded at the draw volumes in the recommended range.
\n
It also needs to be mentioned that if the draw-volume inspection relays on the label mark a judgment can be false. During our first study, we found out that only one brand of the tubes had a label positioned precisely; in all others the indicators on the tube were misleading.
\n
Easy-to-perform testing procedures as we used here which do not require blood samples can as a precautious measure ensure that the tubes are used only if they are of the adequate quality and their quality does not fluctuate too much during the time. It can alert a laboratory when it would be advisable to perform a much more complex and time-demanding verification study on blood samples. Archived data on the tubes’ characteristics and quality during a longer period of time can provide a piece of evidence for other studies and rule the tubes out as a potential cause for variations.
\n
\n
\n
2.3 Tubes’ drawing capability reduces during the time
\n
In this section, we explain the changes in a behavior of the tubes during their shelf life.
\n
The tubes’ drawing capability depends on a difference between the external (p\nst) and internal (p\nint_20°C) pressure. The lower the internal pressure, and the higher the difference to the external pressure, the higher a drawing capability. A tube’s internal volume (V\ntube) also contributes to higher capacity to draw a liquid.
\n
The tubes of different brands differ in their drawing capability and, in a way, how it reduces during the time, as \nFigure 5\n demonstrates. No container is entirely tight and leaks to some extent. The conditions to which the tubes were exposed or under which they were stored contribute. The tubes of the same lot would behave differently in different circumstances.
\n
Figure 5.
Drawing capability of the tubes reduces continuously during their shelf life.
\n
Even though tubes are of a high quality, are purchased at the same time, and are of the same lot, they are not all the same if used during their shelf life. A reduction in a drawing capacity results in a diminished draw volume and enhanced anticoagulant concentration.
\n
The tubes’ validations and verifications with blood samples are essential; however complex and with no insight into characteristics of the tubes as such, it is not clear what was actually tested and how representative it is. The outcomes might vary and can be influenced by a choice of a group of individuals, its representativeness, a normality of a distribution of the investigated parameter, and the sources of uncertainty originating from the whole procedure, comprising pre-analytical, analytical, and post-analytical phases. All these factors can influence the conclusions of a paired t-test or ANOVA, a difference between two brands, or lots of the tubes might turn out insignificant. Insight into tubes’ characteristics can give the verification and validation studies some basic orientation on what was the status of the tubes that were investigated. If the evaluation is repeated later, one can know how comparable are the examined tubes entering the process.
\n
If a difference between the results obtained for the tubes of different brands is confirmed to be statistically significant by the tests performed on blood samples, they are frequently considered not clinically important. However, variations, which are not important on the level of a group of individuals, might reflect differently when a single person is concerned. Personal variations in blood parameters are narrower than variations on the level of a population. A personal medicine and athlete’s biological passport require higher sensitivity and attention paid to all sources of uncertainty.
\n
It is not possible to perform validation study with blood samples for each individual, but it is easily possible to perform a quality control of the tubes which are used for personal profiles.
\n
The athlete’s biological passport (ABP) requires accurate and reliable results of hematological tests, which are stable enough for evaluations of the probabilities of abnormalities in a personal profile. Hence, some parameters, e.g., hemoglobin and erythrocytes, were identified as highly stable; the others such as reticulocytes, mean red blood cell volume, and hematocrit did not turn out as such. Sample storage conditions and treatment and the choice of an analyzer are considered the contributing factors [21].
\n
It was proven that during a training season hemoglobin and hematocrit reduce in their value, and reticulocytes do as well but independently. The pattern is general but the size of a change is sport?s discipline dependent. It was recognized that reliable reference ranges in sportsmen could not be defined without the best laboratory practices [22].
\n
Not univocal and entirely clear outcomes of different studies on the stability of the blood variables raise concerns and request for more clearly defined characteristics, procedures, threshold limits, personal reference ranges, and criteria for recognizing abnormalities to prevent false convictions in athletes [23].
\n
In order to raise awareness to which extent different pre-analytical phases could affect the outcomes of hematological and biochemical tests on which sports medicine depends in following athletes, different pre-analytical aspects and the choice of anticoagulant, instabilities of some molecules were addressed to prevent misinterpretation of data and improve the usefulness of results [24]. Specimen homogenization as a pre-analytical phase received special attention [25].
\n
The variations in tubes’ characteristics did not receive attention in relation to ABP in spite of the fact that easy-to-perform testing procedures are available [7]. They are thoroughly explained in the continuation.
\n
\n
\n
\n
3. A methodology for K3EDTA or K2EDTA evacuated blood-collection tubes’ quality evaluation
\n
A methodology for a quality evaluation of evacuated blood-collection tubes for hematological tests consists of two successive measurements, a measurement of a draw volume and electrolytic conductivity, from which one can predict the anticoagulant concentration in a blood sample. No patient- or person-related samples are required. A medium for the tests is purified water.
\n
Only low-cost equipment, a Bang burette and a field conductivity meter, is used. One also needs to know an ambient temperature and a non-reduced pressure for a period during which measurements were performed. The latter can be obtained from a local meteorological institution on request, and temperature is easy to measure. We explain the testing procedures in full details in the following section.
\n
We previously published the nomograms for K2EDTA and K3EDTA tubes with nominal 3 mL draw volume, which enable a prediction on how is an anticoagulant concentration going to rise with a diminishing draw volume that happens during the time because of the aging of the tubes [7].
\n
In \nFigure 6\n we present a nomogram for the K3EDTA tubes with a 2 mL nominal draw volume relating the electrolytic conductivity, κ, with a predicted anticoagulant concentration, c, and a draw volume, V. The points are the results of the quality evaluation of the tubes of two different brands, E and G, at the particular moment in time. If the tubes in a lot are of a homogenous quality and they are going to be tested later during their shelf life, the anticoagulant concentration as expected for blood samples is going to rise as the curves indicate. In such a case, a draw-volume measurement can already give an insight into the quality of the examined tubes.
\n
Figure 6.
A nomogram for a prediction on how is the anticoagulant concentration in 2 mL K3EDTA tubes of two different brands (E, G) going to change with a declining draw volume; green rectangle outlines the characteristics considered acceptable by H1-A5 standard [5].
\n
If we take the G tubes as an example, for the great majority of the tested tubes, with a draw volume close to 2.1 mL, the anticoagulant concentration anticipated initially was 4.45 mmol/L. If we assume that later in time we find out that the draw volume has fallen to 1.9 mL, the anticoagulant concentration for blood samples is going to be close to 4.95 mmol/L. A green rectangle indicates the limits set by H1-A5 standard [5], demonstrating that the tubes would still have been of adequate quality.
\n
Skills needed to perform the tests are not difficult to master, and a laboratory or medical staff can easily develop them. The quality of the tubes does not deteriorate very rapidly. It is important to test tubes when they are put into use, and later only occasionally, but at regular intervals. Since the tests are not time-consuming and not performed in high numbers, this additional workload does not represent an important additional burden for personnel; however, the benefits for an institution are obvious and important.
\n
An institution implementing a quality evaluation scheme always has an adequate insight into the characteristics and quality of the tubes it is using. It can ensure that the tubes are used only if and only until they are of adequate quality or it can use the data in medical and clinical studies to test possible correlations or covariations.
\n
\n
\n
4. Testing procedures
\n
Testing procedures consist of a draw volume and an electrolytic conductivity measurement (\nFigure 7\n left/right), both later corrected to correspond to a temperature 20°C and an external pressure 101 kPa as required by the standards [5, 6].
\n
Figure 7.
A setup for a draw-volume measurement (left) and a conductivity cell for the anticoagulant concentration estimation (right).
\n
\n
4.1 Draw volume
\n
In the schematic (\nFigure 7\n), far left, an evacuated tube, characterized by an internal pressure (p\nint) and an internal tube volume (V\ntube), defining a conserved energy of withdrawal for a blood specimen collection is depicted.
\n
In the middle, a draw-volume measurement is schematically represented. A starting point is a Bang burette filled with purified water to the 0 mL mark. A tip of the burette is attached to a flexible tubing, which is at the other end connected to a blood-collection device. This part too is entirely filled with purified water. When we attach an evacuated tube to the venipuncture device, the tube starts filling with water, and consequently the water level in the Bang burette starts falling. The rising water level in the tube acts as a moving piston, reducing the void volume and causing the internal pressure to rise until it equals the external pressure (p\next). At this moment, the withdrawing ends, and we can read the draw volume from a burette.
\n
Hence, the external pressure and temperature (T) affect a draw-volume test. The external pressure depends on the altitude and current weather conditions and can be obtained from the local meteorological institution. The ambient temperature is also important and has to be taken into account. It affects the internal pressure in a tube at the instant of the draw-volume measurement. At a higher temperature, the air in the tube expands, the internal pressure rises, or, in other words, the internal under-pressure deteriorates, and a tube’s withdrawing ability falls.
\n
For these two reasons, a draw volume (V\ndraw) should be corrected to obtain an estimation of a draw volume, as it would have been, if measured at 1013 hPa and 20°C (V\ndraw_st) (1); the symbol K and hPa stand for the units Kelvin and hectopascal, respectively:
The standards [5, 6] admit that if the draw volume under these conditions does not differ from the nominal volume for more than 10%, the tubes are expected to be of the adequate quality for a blood specimen collection. For the 3 mL tubes, this means that the draw volumes between 2.7 and 3.3 mL are acceptable.
\n
Even though the standards [3, 4] expose as the main quality issue in a nonconformity of a draw volume with the requirements, our results in Section 2 prove that a draw volume within the acceptable range does not necessarily ensure the correct anticoagulant level. An additional insight into this aspect of quality is necessary. For the K2EDTA and K3EDTA tubes, respectively, a conductance measurement can provide such an insight.
\n
\n
\n
4.2 Ionic conductivity
\n
K2EDTA and K3EDTA are salts, and salt in water dissociates in ions. Solutions containing ions conduct electric current, to which extent depends on the ions’ characteristics and their concentration. In other words, conductance (G) of a solution reflects an overall ionic composition, but, if a solution contains only a single salt, as it is a case for K2EDTA and K3EDTA tubes, it can provide an insight into a salt concentration.
\n
A conductance depends on the geometry of a conductivity cell. A cell we used is depicted in \nFigure 7\n (far right). It was an immersive four-electrode cell, not directly applicable to our needs. We closed the bottom of the cave with a parafilm and the hole at the right with a stopper made of a pipette tip to transform it into a conductivity cell applicable for conductance measurements in solutions of a small volume.
\n
The conductance measurement is affected by a size of electrodes and a distance between them; a cell geometry is reflected in a cell constant K. If the results of measurements are expressed as ionic conductivity (κ), they are universally useful and comparable between different measuring systems (2):
\n
\n\nκ\n=\nG\n×\nK\n\nE2
\n
Another concern is a temperature during a measurement; it also affects the conductance value. At higher temperatures, a conductance is higher. This is taken into account by reporting an ionic conductivity at a selected reference temperature, e.g., 20°C. Measurements obtained at an ambient temperature are transformed into the values as would have been at the reference temperature by taking a temperature compensation into account. A linear compensation is frequently used; a compensation factor is usually approximately 2%/°C. In our case, the values confirmed experimentally were 1.99 or 2.01% for K3EDTA or K2EDTA, respectively.
\n
Conductivity measurements are in fact easy to perform. A conductivity cell has a temperature sensor incorporated. We select the reference temperature, define a temperature compensation factor and a cell constant, and perform measurements.
\n
\n
\n
4.3 Anticoagulant concentration
\n
For a solution of a single salt, electrolytic conductivity values are easy to transform into a salt amount concentration, c. If one prepares a set of the solutions with the known salt concentrations and determines their electrolytic conductivity at the reference temperature, one can relate the two parameters by depicting a graph, with the first parameter on the abscise axis, and the second on the ordinate, defining a trend line \n(3)\n:
\n
\n\nκ\n=\na\n+\nb\n×\nc\n\nE3
\n
The symbols, a and b, are the parameter of the linear equation; a stands for the intercept and b for the slope.
\n
After these two parameters are known, one can measure the electrolytic conductivity of the anticoagulant solution obtained after a draw-volume test to obtain κ\n\nV_draw and use the equation in a rearranged form to calculate a concentration of the anticoagulant, c\n\nV_draw(4):
This concentration is valid at the draw volume, but one wants to know the anticoagulant concentration as expected in blood after a specimen collection, c\n\nV_draw_st. As already explained, the draw volume had to be corrected to obtain an estimation of a blood sample volume; a concentration is volume dependent, and therefore it has to be corrected too, to correctly represent the anticoagulant concentration as expected after a blood specimen collection (5):
Draw volume and anticoagulant concentration determination can be implemented into laboratory quality control routines. If followed during the time in a form of control charts, they can ensure that the tubes are used only if and only until they are of adequate quality.
\n
\n
\n
\n
5. Citrate tubes a distinct case
\n
The same testing procedure for a draw-volume measurement is applicable also to citrate tubes. However, in terms of a determination of the anticoagulant concentration, this is a distinct case. The reason is that citrate in the tubes can be either buffered or unbuffered. As a result, a solution after a draw-volume test can have quite a different pH and contains different citrate equilibrium forms in different proportions. For this reason measurement of electrolytic conductivity cannot be used here, and an adequate low-cost and easy-to-perform testing procedure yet has to be developed.
\n
We evaluated the citrate tubes of two different brands, A and B. Both were (1:9) type tubes but differed in nominal draw volumes, which were 4.5 and 3.6 mL for tubes A and B, respectively. Measured draw volumes that we obtained were 4.55 and 3.47 mL; it has to be pointed out that these are uncorrected values.
\n
Getting insight into the composition of the anticoagulant solution after a draw-volume test is possible, but the approach is complex and time-consuming. We used two ion chromatographic techniques, ion-exclusion chromatography for determination of citrate and ion-exchange chromatography for determination of cations.
\n
\n\nFigure 8\n depicts chromatograms obtained for determinations of cations after a draw-volume test. Four chromatographic peaks emerge. The first peak appearing between 4 and 6 minutes pertains to the major cation, sodium, originating from the anticoagulant, trisodium citrate. This peak is presented twice with two different y-axis scales, in the main chromatogram with its top is out of scale and in the inserted frame where it is fully visible.
\n
Figure 8.
Chromatograms for determination of sodium, potassium, magnesium, and calcium in the tubes of two different brands, A and B, after a draw-volume test.
\n
The peak for the A brand tubes is smaller, indicating that in this case citrate is buffered, while in addition to sodium ions there are hydronium ions (H+, or H3O+) to neutralize a negative charge of citrate equilibrium forms. In other words, in the case of the A brand tubes, the anticoagulant solution was prepared not only from a trisodium citrate but also with an addition of citric acid. Consequently, the pH of a solution is lower than with the B brand tubes; the pH results we obtained were 6.1 and 7.9, correspondingly.
\n
As \nFigure 8\n demonstrates, we also confirmed the presence of potassium, a peak between 6 and 8 minutes; magnesium, a peak at around 10 minutes; and calcium, a peak at around 12 minutes.
\n
Presence of magnesium came with no surprise; authors using a different analytical method previously reported on it and explained that it leaks from a closure and originates from an additive [1]. Though we confirmed a difference between A and B brand tubes, the latter contained magnesium in much lower concentration.
\n
The concentration of calcium is low in both cases and might be considered an impurity originating from other chemicals. But what makes a real difference between the tubes of the two brands and was not expected is potassium. While it is nearly inexistent in tube B, it is obviously present in tube A. We used infrared spectroscopy to explain where it originates from; it appears that the source might be a tripotassium salt of EDTA; if this is the case, its concentration is approximately 200 times lower than the citrate concentration.
\n
\n
\n
6. Conclusions
\n
This research proved differences in characteristics of tubes of different brands and different lots, and their attributes are also changing during a shelf life. We suggested fast, easy-to-perform testing procedures, which already by using purified water and low-cost equipment only give an insight into draw volume and anticoagulant concentration as can be expected for a blood specimen collection.
\n
No doubt, a laboratory has to prove on blood samples that a particular type of tubes it is using or intends to use is fit for purpose. But already with a minimum required number of samples of 20 individuals, a study becomes complex, professionally demanding, and time-consuming. However, not knowing the characteristics of the tubes entering the investigation lacks generality.
\n
Testing procedures as suggested are not to replace but to support such investigations and to make them more economical. A quality control of the tubes as such is easy to introduce into a laboratory practice and does not importantly contribute to a workload. The tubes do not change very rapidly over the time and do not need to be tested very frequently if of the same lot. However, insight into their characteristics provides guidance when a study on blood samples needs to step in to cover important distinctive conditions a laboratory is likely to face during its everyday routine.
\n
A draw-volume test we described is generally applicable. Procedures for determining K2EDTA and K3EDTA concentrations in the tubes before a specimen collection are well established; nevertheless comparably easy-to-perform testing procedures for citrate tubes yet need to be developed.
\n
\n
Acknowledgments
\n
A financial support of the ARRS research program P-153a is acknowledged.
\n
Conflict of interest
No conflicts of interest are declared by the authors.
\n',keywords:"evacuated blood-collection tubes, K3EDTA, K2EDTA, citrate, quality evaluation, draw-volume measurement, anticoagulant concentration",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/63692.pdf",chapterXML:"https://mts.intechopen.com/source/xml/63692.xml",downloadPdfUrl:"/chapter/pdf-download/63692",previewPdfUrl:"/chapter/pdf-preview/63692",totalDownloads:1068,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:47,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"May 5th 2018",dateReviewed:"August 2nd 2018",datePrePublished:"November 5th 2018",datePublished:"April 29th 2020",dateFinished:"September 20th 2018",readingETA:"0",abstract:"Pre-analytical steps contribute to an overall quality of the results of laboratory trials. The volume of blood drawn into the blood-collection tube and the anticoagulant amount introduced into the tube during its production should ensure the anticoagulant level in the recommended range; otherwise, the results can be altered. In evacuated blood-collection tubes, the internal under-pressure at the instant of the blood specimen collection affects the draw volume. During the shelf life, the internal under-pressure deteriorates. With no testing procedures in place, inappropriate anticoagulant levels can pass unnoticed. The chapter details testing procedures ensuring that the tubes are used only if, and only until, they are of the adequate quality. The reasoning behind the methodology is fully explained, and the case studies of the quality evaluations are discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/63692",risUrl:"/chapter/ris/63692",book:{id:"7012",slug:"biochemical-testing-clinical-correlation-and-diagnosis"},signatures:"Nataša Gros",authors:[{id:"171229",title:"Dr.",name:"Nataša",middleName:null,surname:"Gros",fullName:"Nataša Gros",slug:"natasa-gros",email:"natasa.gros@fkkt.uni-lj.si",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Ljubljana",institutionURL:null,country:{name:"Slovenia"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Quality of evacuated blood-collection tubes for hematological tests reevaluated in 5 years’ time",level:"1"},{id:"sec_2_2",title:"2.1 K3EDTA tubes",level:"2"},{id:"sec_3_2",title:"2.2 K2EDTA tubes",level:"2"},{id:"sec_4_2",title:"2.3 Tubes’ drawing capability reduces during the time",level:"2"},{id:"sec_6",title:"3. A methodology for K3EDTA or K2EDTA evacuated blood-collection tubes’ quality evaluation",level:"1"},{id:"sec_7",title:"4. Testing procedures",level:"1"},{id:"sec_7_2",title:"4.1 Draw volume",level:"2"},{id:"sec_8_2",title:"4.2 Ionic conductivity",level:"2"},{id:"sec_9_2",title:"4.3 Anticoagulant concentration",level:"2"},{id:"sec_11",title:"5. Citrate tubes a distinct case",level:"1"},{id:"sec_12",title:"6. Conclusions",level:"1"},{id:"sec_13",title:"Acknowledgments",level:"1"},{id:"sec_16",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'\nvan den Besselaar A, van Dam W, Sturk A, Bertina RM. Prothrombin time ratio is reduced by magnesium contamination in evacuated blood collection tubes. Thrombosis and Haemostasis. 2001;85(4):647-650\n'},{id:"B2",body:'\nvan den Besselaar A, van Vlodrop IJH, Berendes PB, Cobbaert CM. A comparative study of conventional versus new, magnesium-poor Vacutainer (R) sodium citrate blood collection tubes for determination of prothrombin time and INR. Thrombosis Research. 2014;134(1):187-191. DOI: 10.1016/j.thromres.2014.04.016\n'},{id:"B3",body:'\nCLSI. Tubes and Additives for Venous and Capillary Blood Specimen Collection. Approved Standard Sixth Edition. CLSI document GP39-A6. Wayne, PA: Clinical and Laboratory Standards Institute; 2010\n'},{id:"B4",body:'\nCLSI. Validation and Verification of Tubes for Venous and Capillary Blood Specimen Collection. Approved Guideline. CLSI document GP34-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2010\n'},{id:"B5",body:'\nNCCLS. Tubes and Additives for Venous Blood Specimen Collection. Approved Standard Fifth Edition. NCCLS document H1-A5. Wayne, Pennsylvania: NCCLS; 2003\n'},{id:"B6",body:'\nDIN ISO 6710: 1996-12 Single-Use Containers for Venous Blood Specimen Collection. 1996\n'},{id:"B7",body:'\nGros N. Evacuated blood-collection tubes for haematological tests—A quality evaluation prior to their intended use for specimen collection. Clinical Chemistry and Laboratory Medicine. 2013;51(5):1043-1051. DOI: 10.1515/cclm-2012-0507\n'},{id:"B8",body:'\nBanfi G, Salvagno GL, Lippi G. The role of ethylenedimine tetraacetic acid (EDTA) as in vitro anticoagulant for diagnostic purposes. Clinical Chemistry and Laboratory Medicine. 2007;45(5):565-576. DOI: 10.1515/cclm.2007.110\n'},{id:"B9",body:'\nZandecki M, Genevieve F, Gerard J, Godon A. Spurious counts and spurious results on haematology analysers: A review. Part I: Platelets. International Journal of Laboratory Hematology. 2007;29(1):4-20. DOI: 10.1111/j.1365-2257.2006.00870.x\n'},{id:"B10",body:'\nZandecki M, Genevieve F, Gerard J, Godon A. Spurious counts and spurious results on haematology analysers: A review. Part II: White blood cells, red blood cells, haemoglobin, red cell indices and reticulocytes. International Journal of Laboratory Hematology. 2007;29(1):21-41. DOI: 10.1111/j.1365-2257.2006.00871.x\n'},{id:"B11",body:'\nAlmagor M, Lavid-Levy O. Effects of blood-collection systems and tubes on hematologic, chemical, and coagulation tests and on plasma hemoglobin. Clinical Chemistry. 2001;47(4):794-795\n'},{id:"B12",body:'\nvan den Besselaar A, Chantarangkul V, Tripodi A. A comparison of two sodium citrate concentrations in two evacuated blood collection systems for prothrombin time and ISI determination. Thrombosis and Haemostasis. 2000;84(4):664-667\n'},{id:"B13",body:'\nTripodi A, Chantarangkul V, Bressi C, Mannucci PM. How to evaluate the influence of blood collection systems on the international sensitivity index. Protocol applied to two new evacuated tubes and eight coagulometer/thromboplastin combinations. Thrombosis Research. 2002;108(1):85-89. DOI: 10.1016/s0049-3848(02)00383-3\n'},{id:"B14",body:'\nKratz A, Stanganelli N, Van Cott EM. A comparison of glass and plastic blood collection tubes for routine and specialized coagulation assays—A comprehensive study. Archives of Pathology & Laboratory Medicine. 2006;130(1):39-44\n'},{id:"B15",body:'\nTetrault GA. Comparison of glass and plastic blood collection tubes. Archives of Pathology & Laboratory Medicine. 2006;130(11):1600\n'},{id:"B16",body:'\nToulon P, Aillaud MF, Arnoux D, Boissier E, Borg JY, Gourmel C. Multicenter evaluation of a bilayer polymer blood collection tube for coagulation testing: Effect on routine hemostasis test results and on plasma levels of coagulation activation markers. Blood Coagulation & Fibrinolysis. 2006;17(8):625-631. DOI: 10.1097/01.mbc.0000252595.79282.86\n'},{id:"B17",body:'\nYavas S, Ayaz S, Kose SK, Ulus F, Ulus AT. Influence of blood collection systems on coagulation tests. Turkish Journal of Hematology. 2012;29(4):367-375. DOI: 10.5505/tjh.2012.59254\n'},{id:"B18",body:'\nD\'Angelo G, Villa C. Comparison between siliconized evacuated glass and plastic blood collection tubes for prothrombin time and activated partial thromboplastin time assay in normal patients, patients on oral anticoagulant therapy and patients with unfractioned heparin therapy. International Journal of Laboratory Hematology. 2011;33(2):219-225. DOI: 10.1111/j.1751-553X.2010.01271.x\n'},{id:"B19",body:'\nXu M, Robbe VA, Jack RM, Rutledge JC. Under-filled blood collection tubes containing K(2)EDTA as anticoagulant are acceptable for automated complete blood counts, white blood cell differential, and reticulocyte count. International Journal of Laboratory Hematology. 2010;32(5):491-497. DOI: 10.1111/j.1751-553X.2009.01211.x\n'},{id:"B20",body:'\nBiljak VR, Bozicevic S, Krhac M, Lovrencic MV. Impact of under-filled blood collection tubes containing K(2)EDTA and K(3)EDTA as anticoagulants on automated complete blood count (CBC) testing. Clinical Chemistry and Laboratory Medicine. 2016;54(11):E323-E3E6. DOI: 10.1515/cclm-2016-0169\n'},{id:"B21",body:'\nLombardi G, Lanteri P, Colombini A, Lippi G, Banfi G. Stability of haematological parameters and its relevance on the athlete’s biological passport model. Sports Medicine. 2011;41(12):1033-1042\n'},{id:"B22",body:'\nBanfi G, Lundby C, Robach P, Lippi G. Seasonal variations of haematological parameters in athletes. European Journal of Applied Physiology. 2011;111(1):9-16. DOI: 10.1007/s00421-010-1641-1\n'},{id:"B23",body:'\nSanchis-Gomar F, Martinez-Bello VE, Gomez-Cabrera MC, Vina J. Current limitations of the athlete’s biological passport use in sports. Clinical Chemistry and Laboratory Medicine. 2011;49(9):1413-1415. DOI: 10.1515/cclm.2011.609\n'},{id:"B24",body:'\nBanfi G, Dolci A. Preanalytical phase of sport biochemistry and haematology. The Journal of Sports Medicine and Physical Fitness. 2003;43(2):223-230\n'},{id:"B25",body:'\nAshenden M, Clarke A, Sharpe K, d\'Onofrio G, Allbon G, Gore CJ. Preanalytical mixing of whole-blood specimens in the context of the athlete passport. Journal of Clinical Pathology. 2012;65(1):8-13. DOI: 10.1136/jclinpath-2011-200269\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Nataša Gros",address:"natasa.gros@fkkt.uni-lj.si",affiliation:'
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia
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1. Introduction
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Evacuated blood-collection tubes are evacuated containers intended for a venous blood specimen collection. They consist of a tube and a closure, which has to be tight to restrain low pressure—vacuum inside the tubes during their shelf life—but, on the other hand, it also has to be soft enough to let a sharp end of a blood-collection device to penetrate into a tube. The collection device has a disposable needle attached to the other side for phlebotomy.
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Evacuated blood-collection tubes improved patients’ and medical personnel’s safety and mostly replaced classical tubes, which required a syringe and a needle for a specimen collection. In a continuation, wherever a tube is mentioned, the evacuated blood-collection tube is meant.
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To prevent blood coagulation, tubes contain anticoagulants, either as dry substances attached to the internal walls or as solutions. Widely known and used are sodium citrate and salts of ethylenediaminetetraacetic acid (EDTA), usually present either as dipotassium or tripotassium salts, K2EDTA or K3EDTA.
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Other substances, additives might be introduced as well to ensure the adequate properties or behavior of the tubes’ internal walls or closures; nevertheless, they are expected not to interfere with a determination and affect analytical results. A noncompliant constituent detected in citrate tubes was magnesium which leached from a stopper and was consequently influencing the prothrombin time (PT) results [1]. A comprehensive study evaluating different tubes comprising also recently introduced low-magnesium version confirmed that the PT and INR differences between the tubes are correlated with the magnesium concentration differences [2].
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Manufacturers are obliged to specify on the label of a tube: a type of anticoagulant, a nominal draw volume, a lot number, and expiration date; within this text, we use a term expiry date as well.
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Anticoagulant concentration in a blood sample after specimen collection should be within an appropriate range; otherwise, analytical results might be altered. To reach this objective, an accurate amount of anticoagulant should be introduced into a tube during production, and a draw at the moment of a specimen collection should be adequate to ensure a volume of blood entering a tube is within an acceptable range. A label on a tube provides guidance for inspection if the volume is within the suggested limits; however, this is only true if the label is precisely and accurately positioned.
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The latest version of the GP39-A6 standard of the CLSI standardization body (Clinical and Laboratory Standards Institute) [3] requires of the tubes’ manufacturers to ensure that until expiration date, the anticoagulant concentration remains within the 5% range of the value stated on a label. A draw volume is considered acceptable if it does not differ from the stated nominal volume for more than ±10%.
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The standard GP34-A recognizes the importance of appropriate blood-to-EDTA ratio for obtaining optimal examination results but avoids stating the exact limits. The EDTA can, if in a concentration which is too high hypertonically shrink red cells, affect red cell size and cause morphological changes. On the other hand, it can too extensively chelate calcium and other cations such as magnesium and zinc and affect the activity of alkaline phosphatase enzyme label used in chemiluminescent assays or reduce the efficiency of the recognition of proteins by antibodies due to the proteins’ conformation changes [4].
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The predecessor of CLSI, the National Committee for Clinical Laboratory Standards (NCLLS), was in the H1-A5 standard more explicit in terms of some anticoagulants’ concentrations [5]. It explains that only a little bit less than a half (1.15 mmol/L) out of the total calcium concentration (2.5 mmol/L) corresponds to unbound calcium that needs to be chelated stoichiometrically with EDTA to prevent coagulation. For that reason, it suggests that EDTA concentration in blood should be between 3.7 and 5.4 mmol/L, since excessive concentration causes morphological changes in the blood.
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Not consistent with this requirement was DIN ISO 6710: 1996-12 standard requiring the EDTA concentration within the 4.11–6.843 mmol/L range [6].
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A potential user can during time come across the tubes which were produced by not having the same set of requirements on the mind. As we already previously demonstrated, the tubes if evaluated as such not yet in contact with a blood sample are not all the same, and change in their own characteristics during their shelf life and the testing procedure which we suggested are easy to perform [7].
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A concise review reflects on the behavior of EDTA as an anticoagulant in hematology and furthermore discusses its usage in proteomics, general clinical chemistry, and its applicability for measuring cytokines, protein, peptides, and cardiac markers [8]. Elsewhere, influences of a form of EDTA and its concentration on the results of hematological tests were profoundly discussed in relation to spurious counts and results regarding platelets [9], white blood cells, red blood cells, hemoglobin, red cell indices, and reticulocytes [10]; under-filled or over-filled evacuated tubes changing the anticoagulant level in a sample are exposed as an influential pre-analytical source of errors.
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For citrate tubes the DIN ISO 6710: 1996-12 standard recommends trisodium citrate solutions with concentrations between 100 and 136 mmol/L; however, the H1-A5 standard specifies the concentrations 105, 109, and 129 mmol/L.
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Due to all these differences, the GP39-A6 standard omitted all the anticoagulant concentrations’ details, leaving it entirely to a producer to bear the responsibility for securing appropriate concentration, fulfilling all the requirements, and demonstrating that they are actually met, or in other words verifying that the tubes are actually fit for purpose.
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The GP34-A standard provides guidance for validation and verification of tubes for venous and capillary blood specimen collection [4]. Both a manufacturer and a clinical laboratory are required to perform a comparability study on blood samples for two or more sets of tubes comprising a set which was already evaluated and approved previously. A manufacturer performs such a test after a new product was developed or where any correction actions are necessary for the production process. The laboratory needs to do it when switching from one product to another or when changing a vendor.
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A within-tube precision study requires a minimum of 20 subjects, and each sample needs to be analyzed in replicates; an appropriate number of samples, evenly distributed through the analytical measurement, are essential for trueness evaluation [4]. Several studies with sometimes dissimilar outcomes can be found in the literature.
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Two blood-collection devices either with an aligned [Becton Dickinson (BD)] or at an angle needle holder (Greiner Labortechnik GmbH) were evaluated either enabling a direct linear (BD) or interrupted nonlinear blood flow. A mechanical strain on blood cells was recognized as a factor potentially causing the efflux of intracellular constituents into the serum in an interrupted nonlinear flow. The magnesium, plasma hemoglobin, and prothrombin time within-subject variations were confirmed in 55 healthy individuals using a Student paired t-test. A difference in a tube material either glass or polymer was also recognized as a likely contributing factor [11].
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Nevertheless, contrasting outcomes were obtained for prothrombin time determinations in the glass and PVC tubes with two distinct citrate concentrations where neither material caused the significantly different results [12]. Yet another study, establishing a protocol for comparing the citrate evacuation blood-collection tubes with glass tubes employing eight measuring systems, confirmed a statistically significant but clinically not relevant difference in prothrombin time results, which were more pronounced with the tubes of the lowest 2.7 mL draw volume [13].
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Differences in some parameters were confirmed if BD plastic citrate tubes were used instead of glass tubes, but they were considered unlikely to be clinically significant [14], though a comprehensiveness of a study was challenged arguing that only healthy volunteers were involved and by these means it was not yet proven that glass tubes are interchangeable with the plastic tubes [15]. But a study performed on Greiner glass citrate and plastic tubes confirmed that the tubes are substitutable as far as either untreated or patients on a traditional oral anticoagulant therapy are concerned and that this applies for the whole shelf life of the tubes [16].
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Nevertheless, the plastic tubes of different brands evaluated on patients and healthy volunteers were confirmed to be statistically but not clinically significantly different [17]. For patients on oral anticoagulant therapy with vitamin K antagonists, ANOVA test confirmed statistically significant differences in prothrombin time for the tubes of four different types [18]. The study supports the claim that validation is always necessary when there is a change in a tube type.
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A research performed on a group of individuals evaluating the effect of under-filled EDTA tubes on hematological parameters by employing a particular type of analyzer [19] leads to contrasting outcomes not necessarily aligned with other studies [20] and general principles and recommendations.
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Validations and verifications as required by the standard GP34-A are complex to perform, time demanding, and require resourceful personnel [4].
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The standard exposes a blood collection as a pre-analytical (preexamination) source causing varying degrees of errors. It brings to light a lack of a mechanism that would enable systematic evaluations of the influences of pre-analytical (preexamination) variables on laboratory test (examination) results [4].
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The characteristics of the tubes entering the pre-analytical phase are such variables, and this is where this chapter tends to contribute.
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Differences between tubes of different brands examined 5 years apart in time are going to be enlightened, and the testing procedures which are fast, cheap, and easy to implement into laboratory practice are explained in full details. Robustness of personal profiles of athletes and validation studies performed on blood samples can profit from knowing the attributes of the tubes that were actually used or evaluated.
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2. Quality of evacuated blood-collection tubes for hematological tests reevaluated in 5 years’ time
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In this section, we compare the results of a quality evaluation of the blood-collection tubes, on which we previously reported [7], with the results obtained in 5 years’ time. The same producers were considered, namely, Becton Dickinson, Greiner Bio-One, and Laboratorijska tehnika Burnik d. o. o.
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\n\nFigures 1\n–\n4\n are dedicated to the tubes of four different brands. The abscise axis stands for a draw volume. Ordinate on the right indicates an anticoagulant concentration expected for a blood sample after a specimen collection. We are going to explain the meaning of the left ordinate axis, which relates to a testing procedure, later. A frame in green indicates the limits set by the H1-A5 standard [5]. The horizontal lines confine the range of the acceptable anticoagulant concentration; the left vertical line represents a limit under which a draw volume is expected not to fall to prevent the anticoagulant concentration to rising too high.
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Figure 1.
Anticoagulant concentrations and draw volumes of the A brand tubes obtained 5 years apart in time (orange/blue) and of the tubes F not previously included (the numbers in the labels indicate time until the expiration).
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Figure 2.
Anticoagulant concentrations and draw volumes of the B brand tubes obtained 5 years apart in time (orange/blue); the numbers in the labels indicate the time until the expiration.
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Figure 3.
Anticoagulant concentrations and draw volumes of the C brand tubes obtained 5 years apart in time (orange/blue); the numbers in the labels indicate the time until the expiration.
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Figure 4.
Anticoagulant concentrations and draw volumes of the D brand tubes obtained 5 years apart in time (orange/blue); the numbers in the labels indicate the time until the expiration.
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We kept the assigned marks A, B, and C from the previous study for the K3EDTA tubes, and D for the K2EDTA tubes, not disclosing the producers’ identity. We additionally included the tubes F, not previously evaluated. The more recent results are marked with an asterisk; a number indicates the number of days until the expiration.
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Ellipses in \nFigures 1\n–\n4\n provide an insight into a spread of results obtained for the tubes within a series of measurements. Ellipses in blue correspond to the more recent results; those in orange originate from a previous study. A length of a horizontal axis of an ellipse equals a standard deviation of the draw-volume measurements; a vertical axis indicates a standard deviation of the anticoagulant concentration as expected for blood samples. A crossing of the two axes of an ellipse is defined by the mean values of the two parameters. The smaller the ellipse, the higher the quality of the produced tubes in terms of their precision or, in other words, a repeatability of a product.
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2.1 K3EDTA tubes
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From this point of view, the A brand tubes were and remain of a high quality. In spite of having a very long expiration date, unless very close to the expiration (A*18), the draw volumes generally remain adequate; however, the anticoagulant concentration is too high and not in the accordance with the higher limit set by the H1-A5 standard [5]. All the ellipses of the A brand tubes are above the green rectangle in \nFigure 1\n. The same is true for the tubes F, which are of the same manufacturer. This example demonstrates that an adequate draw volume does not yet ensure the adequate anticoagulant concentration as far as the H1-A5 is concerned. The tubes were obviously produced following an older DIN ISO 6710: 1996-12 standard, for which the anticoagulant concentration 6.843 mmol/L was still acceptable. With this limit in mind, only the A*18A anticoagulant concentration would be excessive. The characteristics of these tubes clearly contrast those of the tubes B and C, as the figures in the continuation demonstrate.
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In the B brand tubes (\nFigure 2\n), an improvement in the overall quality of the results is evident in 5 years’ time. Previously the ellipses were much larger, and they exceeded the upper anticoagulant concentration limit even with the draw volumes very close to the nominal 3 mL mark. The ellipses in blue are small and remain within the green rectangle during the whole shelf life; nevertheless it has to be mentioned the shelf life was at the time of purchase much shorter than in the A brand tubes.
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The C brand tubes exhibit a good repeatability of the product; however, the anticoagulant concentration starts exceeding slightly the higher-anticoagulant concentration limit already with the draw volumes approaching 2.8 mL, proving that the draw volume within the acceptable range does not yet guarantee the correct anticoagulant concentration.
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\n
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2.2 K2EDTA tubes
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The product repeatability of the D brand tubes is good, but the anticoagulant concentration starts exceeding the upper limit already approximately 200 days before the expiration date and with the draw volumes falling below 2.9 mL what is far above the acceptable lower limit.
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This study confirmed that a control of a draw volume is not the main quality issue and does not ensure that the anticoagulant concentration is adequate. Only in four cases, the draw volumes below the 2.7 mL limit were observed, and this only happened when the tubes were tested closer than 20 days before their expiration date. On the other hand, in more than 20 cases, the anticoagulant concentration limit as set by the H1-A5 standard was exceeded at the draw volumes in the recommended range.
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It also needs to be mentioned that if the draw-volume inspection relays on the label mark a judgment can be false. During our first study, we found out that only one brand of the tubes had a label positioned precisely; in all others the indicators on the tube were misleading.
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Easy-to-perform testing procedures as we used here which do not require blood samples can as a precautious measure ensure that the tubes are used only if they are of the adequate quality and their quality does not fluctuate too much during the time. It can alert a laboratory when it would be advisable to perform a much more complex and time-demanding verification study on blood samples. Archived data on the tubes’ characteristics and quality during a longer period of time can provide a piece of evidence for other studies and rule the tubes out as a potential cause for variations.
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2.3 Tubes’ drawing capability reduces during the time
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In this section, we explain the changes in a behavior of the tubes during their shelf life.
\n
The tubes’ drawing capability depends on a difference between the external (p\nst) and internal (p\nint_20°C) pressure. The lower the internal pressure, and the higher the difference to the external pressure, the higher a drawing capability. A tube’s internal volume (V\ntube) also contributes to higher capacity to draw a liquid.
\n
The tubes of different brands differ in their drawing capability and, in a way, how it reduces during the time, as \nFigure 5\n demonstrates. No container is entirely tight and leaks to some extent. The conditions to which the tubes were exposed or under which they were stored contribute. The tubes of the same lot would behave differently in different circumstances.
\n
Figure 5.
Drawing capability of the tubes reduces continuously during their shelf life.
\n
Even though tubes are of a high quality, are purchased at the same time, and are of the same lot, they are not all the same if used during their shelf life. A reduction in a drawing capacity results in a diminished draw volume and enhanced anticoagulant concentration.
\n
The tubes’ validations and verifications with blood samples are essential; however complex and with no insight into characteristics of the tubes as such, it is not clear what was actually tested and how representative it is. The outcomes might vary and can be influenced by a choice of a group of individuals, its representativeness, a normality of a distribution of the investigated parameter, and the sources of uncertainty originating from the whole procedure, comprising pre-analytical, analytical, and post-analytical phases. All these factors can influence the conclusions of a paired t-test or ANOVA, a difference between two brands, or lots of the tubes might turn out insignificant. Insight into tubes’ characteristics can give the verification and validation studies some basic orientation on what was the status of the tubes that were investigated. If the evaluation is repeated later, one can know how comparable are the examined tubes entering the process.
\n
If a difference between the results obtained for the tubes of different brands is confirmed to be statistically significant by the tests performed on blood samples, they are frequently considered not clinically important. However, variations, which are not important on the level of a group of individuals, might reflect differently when a single person is concerned. Personal variations in blood parameters are narrower than variations on the level of a population. A personal medicine and athlete’s biological passport require higher sensitivity and attention paid to all sources of uncertainty.
\n
It is not possible to perform validation study with blood samples for each individual, but it is easily possible to perform a quality control of the tubes which are used for personal profiles.
\n
The athlete’s biological passport (ABP) requires accurate and reliable results of hematological tests, which are stable enough for evaluations of the probabilities of abnormalities in a personal profile. Hence, some parameters, e.g., hemoglobin and erythrocytes, were identified as highly stable; the others such as reticulocytes, mean red blood cell volume, and hematocrit did not turn out as such. Sample storage conditions and treatment and the choice of an analyzer are considered the contributing factors [21].
\n
It was proven that during a training season hemoglobin and hematocrit reduce in their value, and reticulocytes do as well but independently. The pattern is general but the size of a change is sport?s discipline dependent. It was recognized that reliable reference ranges in sportsmen could not be defined without the best laboratory practices [22].
\n
Not univocal and entirely clear outcomes of different studies on the stability of the blood variables raise concerns and request for more clearly defined characteristics, procedures, threshold limits, personal reference ranges, and criteria for recognizing abnormalities to prevent false convictions in athletes [23].
\n
In order to raise awareness to which extent different pre-analytical phases could affect the outcomes of hematological and biochemical tests on which sports medicine depends in following athletes, different pre-analytical aspects and the choice of anticoagulant, instabilities of some molecules were addressed to prevent misinterpretation of data and improve the usefulness of results [24]. Specimen homogenization as a pre-analytical phase received special attention [25].
\n
The variations in tubes’ characteristics did not receive attention in relation to ABP in spite of the fact that easy-to-perform testing procedures are available [7]. They are thoroughly explained in the continuation.
\n
\n
\n
\n
3. A methodology for K3EDTA or K2EDTA evacuated blood-collection tubes’ quality evaluation
\n
A methodology for a quality evaluation of evacuated blood-collection tubes for hematological tests consists of two successive measurements, a measurement of a draw volume and electrolytic conductivity, from which one can predict the anticoagulant concentration in a blood sample. No patient- or person-related samples are required. A medium for the tests is purified water.
\n
Only low-cost equipment, a Bang burette and a field conductivity meter, is used. One also needs to know an ambient temperature and a non-reduced pressure for a period during which measurements were performed. The latter can be obtained from a local meteorological institution on request, and temperature is easy to measure. We explain the testing procedures in full details in the following section.
\n
We previously published the nomograms for K2EDTA and K3EDTA tubes with nominal 3 mL draw volume, which enable a prediction on how is an anticoagulant concentration going to rise with a diminishing draw volume that happens during the time because of the aging of the tubes [7].
\n
In \nFigure 6\n we present a nomogram for the K3EDTA tubes with a 2 mL nominal draw volume relating the electrolytic conductivity, κ, with a predicted anticoagulant concentration, c, and a draw volume, V. The points are the results of the quality evaluation of the tubes of two different brands, E and G, at the particular moment in time. If the tubes in a lot are of a homogenous quality and they are going to be tested later during their shelf life, the anticoagulant concentration as expected for blood samples is going to rise as the curves indicate. In such a case, a draw-volume measurement can already give an insight into the quality of the examined tubes.
\n
Figure 6.
A nomogram for a prediction on how is the anticoagulant concentration in 2 mL K3EDTA tubes of two different brands (E, G) going to change with a declining draw volume; green rectangle outlines the characteristics considered acceptable by H1-A5 standard [5].
\n
If we take the G tubes as an example, for the great majority of the tested tubes, with a draw volume close to 2.1 mL, the anticoagulant concentration anticipated initially was 4.45 mmol/L. If we assume that later in time we find out that the draw volume has fallen to 1.9 mL, the anticoagulant concentration for blood samples is going to be close to 4.95 mmol/L. A green rectangle indicates the limits set by H1-A5 standard [5], demonstrating that the tubes would still have been of adequate quality.
\n
Skills needed to perform the tests are not difficult to master, and a laboratory or medical staff can easily develop them. The quality of the tubes does not deteriorate very rapidly. It is important to test tubes when they are put into use, and later only occasionally, but at regular intervals. Since the tests are not time-consuming and not performed in high numbers, this additional workload does not represent an important additional burden for personnel; however, the benefits for an institution are obvious and important.
\n
An institution implementing a quality evaluation scheme always has an adequate insight into the characteristics and quality of the tubes it is using. It can ensure that the tubes are used only if and only until they are of adequate quality or it can use the data in medical and clinical studies to test possible correlations or covariations.
\n
\n
\n
4. Testing procedures
\n
Testing procedures consist of a draw volume and an electrolytic conductivity measurement (\nFigure 7\n left/right), both later corrected to correspond to a temperature 20°C and an external pressure 101 kPa as required by the standards [5, 6].
\n
Figure 7.
A setup for a draw-volume measurement (left) and a conductivity cell for the anticoagulant concentration estimation (right).
\n
\n
4.1 Draw volume
\n
In the schematic (\nFigure 7\n), far left, an evacuated tube, characterized by an internal pressure (p\nint) and an internal tube volume (V\ntube), defining a conserved energy of withdrawal for a blood specimen collection is depicted.
\n
In the middle, a draw-volume measurement is schematically represented. A starting point is a Bang burette filled with purified water to the 0 mL mark. A tip of the burette is attached to a flexible tubing, which is at the other end connected to a blood-collection device. This part too is entirely filled with purified water. When we attach an evacuated tube to the venipuncture device, the tube starts filling with water, and consequently the water level in the Bang burette starts falling. The rising water level in the tube acts as a moving piston, reducing the void volume and causing the internal pressure to rise until it equals the external pressure (p\next). At this moment, the withdrawing ends, and we can read the draw volume from a burette.
\n
Hence, the external pressure and temperature (T) affect a draw-volume test. The external pressure depends on the altitude and current weather conditions and can be obtained from the local meteorological institution. The ambient temperature is also important and has to be taken into account. It affects the internal pressure in a tube at the instant of the draw-volume measurement. At a higher temperature, the air in the tube expands, the internal pressure rises, or, in other words, the internal under-pressure deteriorates, and a tube’s withdrawing ability falls.
\n
For these two reasons, a draw volume (V\ndraw) should be corrected to obtain an estimation of a draw volume, as it would have been, if measured at 1013 hPa and 20°C (V\ndraw_st) (1); the symbol K and hPa stand for the units Kelvin and hectopascal, respectively:
The standards [5, 6] admit that if the draw volume under these conditions does not differ from the nominal volume for more than 10%, the tubes are expected to be of the adequate quality for a blood specimen collection. For the 3 mL tubes, this means that the draw volumes between 2.7 and 3.3 mL are acceptable.
\n
Even though the standards [3, 4] expose as the main quality issue in a nonconformity of a draw volume with the requirements, our results in Section 2 prove that a draw volume within the acceptable range does not necessarily ensure the correct anticoagulant level. An additional insight into this aspect of quality is necessary. For the K2EDTA and K3EDTA tubes, respectively, a conductance measurement can provide such an insight.
\n
\n
\n
4.2 Ionic conductivity
\n
K2EDTA and K3EDTA are salts, and salt in water dissociates in ions. Solutions containing ions conduct electric current, to which extent depends on the ions’ characteristics and their concentration. In other words, conductance (G) of a solution reflects an overall ionic composition, but, if a solution contains only a single salt, as it is a case for K2EDTA and K3EDTA tubes, it can provide an insight into a salt concentration.
\n
A conductance depends on the geometry of a conductivity cell. A cell we used is depicted in \nFigure 7\n (far right). It was an immersive four-electrode cell, not directly applicable to our needs. We closed the bottom of the cave with a parafilm and the hole at the right with a stopper made of a pipette tip to transform it into a conductivity cell applicable for conductance measurements in solutions of a small volume.
\n
The conductance measurement is affected by a size of electrodes and a distance between them; a cell geometry is reflected in a cell constant K. If the results of measurements are expressed as ionic conductivity (κ), they are universally useful and comparable between different measuring systems (2):
\n
\n\nκ\n=\nG\n×\nK\n\nE2
\n
Another concern is a temperature during a measurement; it also affects the conductance value. At higher temperatures, a conductance is higher. This is taken into account by reporting an ionic conductivity at a selected reference temperature, e.g., 20°C. Measurements obtained at an ambient temperature are transformed into the values as would have been at the reference temperature by taking a temperature compensation into account. A linear compensation is frequently used; a compensation factor is usually approximately 2%/°C. In our case, the values confirmed experimentally were 1.99 or 2.01% for K3EDTA or K2EDTA, respectively.
\n
Conductivity measurements are in fact easy to perform. A conductivity cell has a temperature sensor incorporated. We select the reference temperature, define a temperature compensation factor and a cell constant, and perform measurements.
\n
\n
\n
4.3 Anticoagulant concentration
\n
For a solution of a single salt, electrolytic conductivity values are easy to transform into a salt amount concentration, c. If one prepares a set of the solutions with the known salt concentrations and determines their electrolytic conductivity at the reference temperature, one can relate the two parameters by depicting a graph, with the first parameter on the abscise axis, and the second on the ordinate, defining a trend line \n(3)\n:
\n
\n\nκ\n=\na\n+\nb\n×\nc\n\nE3
\n
The symbols, a and b, are the parameter of the linear equation; a stands for the intercept and b for the slope.
\n
After these two parameters are known, one can measure the electrolytic conductivity of the anticoagulant solution obtained after a draw-volume test to obtain κ\n\nV_draw and use the equation in a rearranged form to calculate a concentration of the anticoagulant, c\n\nV_draw(4):
This concentration is valid at the draw volume, but one wants to know the anticoagulant concentration as expected in blood after a specimen collection, c\n\nV_draw_st. As already explained, the draw volume had to be corrected to obtain an estimation of a blood sample volume; a concentration is volume dependent, and therefore it has to be corrected too, to correctly represent the anticoagulant concentration as expected after a blood specimen collection (5):
Draw volume and anticoagulant concentration determination can be implemented into laboratory quality control routines. If followed during the time in a form of control charts, they can ensure that the tubes are used only if and only until they are of adequate quality.
\n
\n
\n
\n
5. Citrate tubes a distinct case
\n
The same testing procedure for a draw-volume measurement is applicable also to citrate tubes. However, in terms of a determination of the anticoagulant concentration, this is a distinct case. The reason is that citrate in the tubes can be either buffered or unbuffered. As a result, a solution after a draw-volume test can have quite a different pH and contains different citrate equilibrium forms in different proportions. For this reason measurement of electrolytic conductivity cannot be used here, and an adequate low-cost and easy-to-perform testing procedure yet has to be developed.
\n
We evaluated the citrate tubes of two different brands, A and B. Both were (1:9) type tubes but differed in nominal draw volumes, which were 4.5 and 3.6 mL for tubes A and B, respectively. Measured draw volumes that we obtained were 4.55 and 3.47 mL; it has to be pointed out that these are uncorrected values.
\n
Getting insight into the composition of the anticoagulant solution after a draw-volume test is possible, but the approach is complex and time-consuming. We used two ion chromatographic techniques, ion-exclusion chromatography for determination of citrate and ion-exchange chromatography for determination of cations.
\n
\n\nFigure 8\n depicts chromatograms obtained for determinations of cations after a draw-volume test. Four chromatographic peaks emerge. The first peak appearing between 4 and 6 minutes pertains to the major cation, sodium, originating from the anticoagulant, trisodium citrate. This peak is presented twice with two different y-axis scales, in the main chromatogram with its top is out of scale and in the inserted frame where it is fully visible.
\n
Figure 8.
Chromatograms for determination of sodium, potassium, magnesium, and calcium in the tubes of two different brands, A and B, after a draw-volume test.
\n
The peak for the A brand tubes is smaller, indicating that in this case citrate is buffered, while in addition to sodium ions there are hydronium ions (H+, or H3O+) to neutralize a negative charge of citrate equilibrium forms. In other words, in the case of the A brand tubes, the anticoagulant solution was prepared not only from a trisodium citrate but also with an addition of citric acid. Consequently, the pH of a solution is lower than with the B brand tubes; the pH results we obtained were 6.1 and 7.9, correspondingly.
\n
As \nFigure 8\n demonstrates, we also confirmed the presence of potassium, a peak between 6 and 8 minutes; magnesium, a peak at around 10 minutes; and calcium, a peak at around 12 minutes.
\n
Presence of magnesium came with no surprise; authors using a different analytical method previously reported on it and explained that it leaks from a closure and originates from an additive [1]. Though we confirmed a difference between A and B brand tubes, the latter contained magnesium in much lower concentration.
\n
The concentration of calcium is low in both cases and might be considered an impurity originating from other chemicals. But what makes a real difference between the tubes of the two brands and was not expected is potassium. While it is nearly inexistent in tube B, it is obviously present in tube A. We used infrared spectroscopy to explain where it originates from; it appears that the source might be a tripotassium salt of EDTA; if this is the case, its concentration is approximately 200 times lower than the citrate concentration.
\n
\n
\n
6. Conclusions
\n
This research proved differences in characteristics of tubes of different brands and different lots, and their attributes are also changing during a shelf life. We suggested fast, easy-to-perform testing procedures, which already by using purified water and low-cost equipment only give an insight into draw volume and anticoagulant concentration as can be expected for a blood specimen collection.
\n
No doubt, a laboratory has to prove on blood samples that a particular type of tubes it is using or intends to use is fit for purpose. But already with a minimum required number of samples of 20 individuals, a study becomes complex, professionally demanding, and time-consuming. However, not knowing the characteristics of the tubes entering the investigation lacks generality.
\n
Testing procedures as suggested are not to replace but to support such investigations and to make them more economical. A quality control of the tubes as such is easy to introduce into a laboratory practice and does not importantly contribute to a workload. The tubes do not change very rapidly over the time and do not need to be tested very frequently if of the same lot. However, insight into their characteristics provides guidance when a study on blood samples needs to step in to cover important distinctive conditions a laboratory is likely to face during its everyday routine.
\n
A draw-volume test we described is generally applicable. Procedures for determining K2EDTA and K3EDTA concentrations in the tubes before a specimen collection are well established; nevertheless comparably easy-to-perform testing procedures for citrate tubes yet need to be developed.
\n
\n
Acknowledgments
\n
A financial support of the ARRS research program P-153a is acknowledged.
\n
Conflict of interest
No conflicts of interest are declared by the authors.
\n',keywords:"evacuated blood-collection tubes, K3EDTA, K2EDTA, citrate, quality evaluation, draw-volume measurement, anticoagulant concentration",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/63692.pdf",chapterXML:"https://mts.intechopen.com/source/xml/63692.xml",downloadPdfUrl:"/chapter/pdf-download/63692",previewPdfUrl:"/chapter/pdf-preview/63692",totalDownloads:1068,totalViews:0,totalCrossrefCites:0,dateSubmitted:"May 5th 2018",dateReviewed:"August 2nd 2018",datePrePublished:"November 5th 2018",datePublished:"April 29th 2020",dateFinished:"September 20th 2018",readingETA:"0",abstract:"Pre-analytical steps contribute to an overall quality of the results of laboratory trials. The volume of blood drawn into the blood-collection tube and the anticoagulant amount introduced into the tube during its production should ensure the anticoagulant level in the recommended range; otherwise, the results can be altered. In evacuated blood-collection tubes, the internal under-pressure at the instant of the blood specimen collection affects the draw volume. During the shelf life, the internal under-pressure deteriorates. With no testing procedures in place, inappropriate anticoagulant levels can pass unnoticed. The chapter details testing procedures ensuring that the tubes are used only if, and only until, they are of the adequate quality. The reasoning behind the methodology is fully explained, and the case studies of the quality evaluations are discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/63692",risUrl:"/chapter/ris/63692",signatures:"Nataša Gros",book:{id:"7012",type:"book",title:"Biochemical Testing",subtitle:"Clinical Correlation and Diagnosis",fullTitle:"Biochemical Testing - Clinical Correlation and Diagnosis",slug:"biochemical-testing-clinical-correlation-and-diagnosis",publishedDate:"April 29th 2020",bookSignature:"Varaprasad Bobbarala, Gaffar Sarwar Zaman, Mohd Nasir Mohd Desa and Abdah Md Akim",coverURL:"https://cdn.intechopen.com/books/images_new/7012.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78985-086-4",printIsbn:"978-1-78985-085-7",pdfIsbn:"978-1-78985-371-1",isAvailableForWebshopOrdering:!0,editors:[{id:"207119",title:"Dr.",name:"Varaprasad",middleName:null,surname:"Bobbarala PhD",slug:"varaprasad-bobbarala-phd",fullName:"Varaprasad Bobbarala PhD"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"171229",title:"Dr.",name:"Nataša",middleName:null,surname:"Gros",fullName:"Nataša Gros",slug:"natasa-gros",email:"natasa.gros@fkkt.uni-lj.si",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Ljubljana",institutionURL:null,country:{name:"Slovenia"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Quality of evacuated blood-collection tubes for hematological tests reevaluated in 5 years’ time",level:"1"},{id:"sec_2_2",title:"2.1 K3EDTA tubes",level:"2"},{id:"sec_3_2",title:"2.2 K2EDTA tubes",level:"2"},{id:"sec_4_2",title:"2.3 Tubes’ drawing capability reduces during the time",level:"2"},{id:"sec_6",title:"3. A methodology for K3EDTA or K2EDTA evacuated blood-collection tubes’ quality evaluation",level:"1"},{id:"sec_7",title:"4. Testing procedures",level:"1"},{id:"sec_7_2",title:"4.1 Draw volume",level:"2"},{id:"sec_8_2",title:"4.2 Ionic conductivity",level:"2"},{id:"sec_9_2",title:"4.3 Anticoagulant concentration",level:"2"},{id:"sec_11",title:"5. Citrate tubes a distinct case",level:"1"},{id:"sec_12",title:"6. Conclusions",level:"1"},{id:"sec_13",title:"Acknowledgments",level:"1"},{id:"sec_16",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'\nvan den Besselaar A, van Dam W, Sturk A, Bertina RM. Prothrombin time ratio is reduced by magnesium contamination in evacuated blood collection tubes. Thrombosis and Haemostasis. 2001;85(4):647-650\n'},{id:"B2",body:'\nvan den Besselaar A, van Vlodrop IJH, Berendes PB, Cobbaert CM. A comparative study of conventional versus new, magnesium-poor Vacutainer (R) sodium citrate blood collection tubes for determination of prothrombin time and INR. Thrombosis Research. 2014;134(1):187-191. DOI: 10.1016/j.thromres.2014.04.016\n'},{id:"B3",body:'\nCLSI. Tubes and Additives for Venous and Capillary Blood Specimen Collection. Approved Standard Sixth Edition. CLSI document GP39-A6. Wayne, PA: Clinical and Laboratory Standards Institute; 2010\n'},{id:"B4",body:'\nCLSI. Validation and Verification of Tubes for Venous and Capillary Blood Specimen Collection. Approved Guideline. CLSI document GP34-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2010\n'},{id:"B5",body:'\nNCCLS. Tubes and Additives for Venous Blood Specimen Collection. Approved Standard Fifth Edition. NCCLS document H1-A5. Wayne, Pennsylvania: NCCLS; 2003\n'},{id:"B6",body:'\nDIN ISO 6710: 1996-12 Single-Use Containers for Venous Blood Specimen Collection. 1996\n'},{id:"B7",body:'\nGros N. Evacuated blood-collection tubes for haematological tests—A quality evaluation prior to their intended use for specimen collection. Clinical Chemistry and Laboratory Medicine. 2013;51(5):1043-1051. DOI: 10.1515/cclm-2012-0507\n'},{id:"B8",body:'\nBanfi G, Salvagno GL, Lippi G. The role of ethylenedimine tetraacetic acid (EDTA) as in vitro anticoagulant for diagnostic purposes. Clinical Chemistry and Laboratory Medicine. 2007;45(5):565-576. DOI: 10.1515/cclm.2007.110\n'},{id:"B9",body:'\nZandecki M, Genevieve F, Gerard J, Godon A. Spurious counts and spurious results on haematology analysers: A review. Part I: Platelets. International Journal of Laboratory Hematology. 2007;29(1):4-20. DOI: 10.1111/j.1365-2257.2006.00870.x\n'},{id:"B10",body:'\nZandecki M, Genevieve F, Gerard J, Godon A. Spurious counts and spurious results on haematology analysers: A review. Part II: White blood cells, red blood cells, haemoglobin, red cell indices and reticulocytes. International Journal of Laboratory Hematology. 2007;29(1):21-41. DOI: 10.1111/j.1365-2257.2006.00871.x\n'},{id:"B11",body:'\nAlmagor M, Lavid-Levy O. Effects of blood-collection systems and tubes on hematologic, chemical, and coagulation tests and on plasma hemoglobin. Clinical Chemistry. 2001;47(4):794-795\n'},{id:"B12",body:'\nvan den Besselaar A, Chantarangkul V, Tripodi A. A comparison of two sodium citrate concentrations in two evacuated blood collection systems for prothrombin time and ISI determination. Thrombosis and Haemostasis. 2000;84(4):664-667\n'},{id:"B13",body:'\nTripodi A, Chantarangkul V, Bressi C, Mannucci PM. How to evaluate the influence of blood collection systems on the international sensitivity index. Protocol applied to two new evacuated tubes and eight coagulometer/thromboplastin combinations. Thrombosis Research. 2002;108(1):85-89. DOI: 10.1016/s0049-3848(02)00383-3\n'},{id:"B14",body:'\nKratz A, Stanganelli N, Van Cott EM. A comparison of glass and plastic blood collection tubes for routine and specialized coagulation assays—A comprehensive study. Archives of Pathology & Laboratory Medicine. 2006;130(1):39-44\n'},{id:"B15",body:'\nTetrault GA. Comparison of glass and plastic blood collection tubes. Archives of Pathology & Laboratory Medicine. 2006;130(11):1600\n'},{id:"B16",body:'\nToulon P, Aillaud MF, Arnoux D, Boissier E, Borg JY, Gourmel C. Multicenter evaluation of a bilayer polymer blood collection tube for coagulation testing: Effect on routine hemostasis test results and on plasma levels of coagulation activation markers. Blood Coagulation & Fibrinolysis. 2006;17(8):625-631. DOI: 10.1097/01.mbc.0000252595.79282.86\n'},{id:"B17",body:'\nYavas S, Ayaz S, Kose SK, Ulus F, Ulus AT. Influence of blood collection systems on coagulation tests. Turkish Journal of Hematology. 2012;29(4):367-375. DOI: 10.5505/tjh.2012.59254\n'},{id:"B18",body:'\nD\'Angelo G, Villa C. Comparison between siliconized evacuated glass and plastic blood collection tubes for prothrombin time and activated partial thromboplastin time assay in normal patients, patients on oral anticoagulant therapy and patients with unfractioned heparin therapy. International Journal of Laboratory Hematology. 2011;33(2):219-225. DOI: 10.1111/j.1751-553X.2010.01271.x\n'},{id:"B19",body:'\nXu M, Robbe VA, Jack RM, Rutledge JC. Under-filled blood collection tubes containing K(2)EDTA as anticoagulant are acceptable for automated complete blood counts, white blood cell differential, and reticulocyte count. International Journal of Laboratory Hematology. 2010;32(5):491-497. DOI: 10.1111/j.1751-553X.2009.01211.x\n'},{id:"B20",body:'\nBiljak VR, Bozicevic S, Krhac M, Lovrencic MV. Impact of under-filled blood collection tubes containing K(2)EDTA and K(3)EDTA as anticoagulants on automated complete blood count (CBC) testing. Clinical Chemistry and Laboratory Medicine. 2016;54(11):E323-E3E6. DOI: 10.1515/cclm-2016-0169\n'},{id:"B21",body:'\nLombardi G, Lanteri P, Colombini A, Lippi G, Banfi G. Stability of haematological parameters and its relevance on the athlete’s biological passport model. Sports Medicine. 2011;41(12):1033-1042\n'},{id:"B22",body:'\nBanfi G, Lundby C, Robach P, Lippi G. Seasonal variations of haematological parameters in athletes. European Journal of Applied Physiology. 2011;111(1):9-16. DOI: 10.1007/s00421-010-1641-1\n'},{id:"B23",body:'\nSanchis-Gomar F, Martinez-Bello VE, Gomez-Cabrera MC, Vina J. Current limitations of the athlete’s biological passport use in sports. Clinical Chemistry and Laboratory Medicine. 2011;49(9):1413-1415. DOI: 10.1515/cclm.2011.609\n'},{id:"B24",body:'\nBanfi G, Dolci A. Preanalytical phase of sport biochemistry and haematology. The Journal of Sports Medicine and Physical Fitness. 2003;43(2):223-230\n'},{id:"B25",body:'\nAshenden M, Clarke A, Sharpe K, d\'Onofrio G, Allbon G, Gore CJ. Preanalytical mixing of whole-blood specimens in the context of the athlete passport. Journal of Clinical Pathology. 2012;65(1):8-13. DOI: 10.1136/jclinpath-2011-200269\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Nataša Gros",address:"natasa.gros@fkkt.uni-lj.si",affiliation:'
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia
'}],corrections:null},book:{id:"7012",type:"book",title:"Biochemical Testing",subtitle:"Clinical Correlation and Diagnosis",fullTitle:"Biochemical Testing - Clinical Correlation and Diagnosis",slug:"biochemical-testing-clinical-correlation-and-diagnosis",publishedDate:"April 29th 2020",bookSignature:"Varaprasad Bobbarala, Gaffar Sarwar Zaman, Mohd Nasir Mohd Desa and Abdah Md Akim",coverURL:"https://cdn.intechopen.com/books/images_new/7012.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78985-086-4",printIsbn:"978-1-78985-085-7",pdfIsbn:"978-1-78985-371-1",isAvailableForWebshopOrdering:!0,editors:[{id:"207119",title:"Dr.",name:"Varaprasad",middleName:null,surname:"Bobbarala PhD",slug:"varaprasad-bobbarala-phd",fullName:"Varaprasad Bobbarala PhD"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"381028",title:"Dr.",name:"Motohiro",middleName:null,surname:"Chosokabe",email:"m2oyama@marianna-u.ac.jp",fullName:"Motohiro Chosokabe",slug:"motohiro-chosokabe",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{id:"55957",title:"A Case of an Invasive Lobular Carcinoma with Extracellular Mucin: Radio-Pathological Correlation",slug:"a-case-of-an-invasive-lobular-carcinoma-with-extracellular-mucin-radio-pathological-correlation",abstract:"A case of 77-year-old female with an invasive lobular carcinoma with extracellular mucin is presented. She felt palpable mass in her left breast. Then, she came to our hospital for further examination. Mammography of right in full view revealed architectural distortion in left upper portion. And ultrasonography demonstrated low-echoic mass about 2 cm in diameter and invasion of the fat tissue was observed. Hence, malignancy was suspected and magnetic resonance imaging (MRI) was performed. MRI findings showed irregular shaped and margined mass with small T2-high-signal intensity. These findings suggested invasive carcinoma with mucin. Because the cancer lesion was not large, partial mastectomy was performed. Interestingly, pathological diagnosis was invasive lobular carcinoma with extracellular mucin. Extracellular mucinous lesion was concordant with small T2-high-signal intensity. This type of carcinoma was previously reported only in three cases, and rare but important, because the treatment and prognosis might change by histological subtypes. We suggest one of the MRI special features of our case is not only irregular shaped and margined mass but also small T2-high-signal intensity. These MR findings might be one of the valuable findings for the diagnosis and differentiation between this type of carcinoma from other tumors.",signatures:"Shinya Tajima, Keiko Kishimoto, Yoshihide Kanemaki, Ichiro Maeda,\nAkira Endo, Motohiro Chosokabe, Takafumi Ono, Koichiro Tsugawa\nand Masayuki Takagi",authors:[{id:"85421",title:"Dr.",name:"Shinya",surname:"Tajima",fullName:"Shinya Tajima",slug:"shinya-tajima",email:"stajima0829@gmail.com"},{id:"381024",title:"Dr.",name:"Keiko",surname:"Kishimoto",fullName:"Keiko Kishimoto",slug:"keiko-kishimoto",email:"keiko.kishimoto@gmail.com"},{id:"381025",title:"Dr.",name:"Yoshihide",surname:"Kanemaki",fullName:"Yoshihide Kanemaki",slug:"yoshihide-kanemaki",email:"yoshihid@tc4.so-net.ne.jp"},{id:"381026",title:"Dr.",name:"Ichiro",surname:"Maeda",fullName:"Ichiro Maeda",slug:"ichiro-maeda",email:"ichirou@marianna-u.ac.jp"},{id:"381027",title:"Dr.",name:"Akira",surname:"Endo",fullName:"Akira Endo",slug:"akira-endo",email:"dummy+381027@intechopen.com"},{id:"381028",title:"Dr.",name:"Motohiro",surname:"Chosokabe",fullName:"Motohiro Chosokabe",slug:"motohiro-chosokabe",email:"m2oyama@marianna-u.ac.jp"},{id:"381029",title:"Dr.",name:"Takafumi",surname:"Ono",fullName:"Takafumi Ono",slug:"takafumi-ono",email:"dummy+381029@intechopen.com"},{id:"381030",title:"Dr.",name:"Koichiro",surname:"Tsugawa",fullName:"Koichiro Tsugawa",slug:"koichiro-tsugawa",email:"koitsuga@marianna-u.ac.j"},{id:"381031",title:"Dr.",name:"Masayuki",surname:"Takagi",fullName:"Masayuki Takagi",slug:"masayuki-takagi",email:"m2takagi@marianna-u .ac .jp"}],book:{id:"6047",title:"Breast Imaging",slug:"new-perspectives-in-breast-imaging",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"4682",title:"Prof.",name:"Yoshihiko",surname:"Kuwahara",slug:"yoshihiko-kuwahara",fullName:"Yoshihiko Kuwahara",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"82546",title:"Dr.",name:"Nachiko",surname:"Uchiyama",slug:"nachiko-uchiyama",fullName:"Nachiko Uchiyama",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/82546/images/3212_n.jpg",biography:"Nachiko Uchiyama M.D. graduated from Nippon Medical School, \nTokyo, Japan in 1992 and was trained as trainee at Nippon Medical \nSchool from 1992 to 1994 and as resident and chief resident at \nDepartment of Diagnostic Radiology, National Cancer Center, Tokyo, Japan from 1994 to 1999. After residency, she worked as Assistant Professor at Department of Radiology, Nippon Medical School from 1999 to 2003. From 2003 to 2007, she worked as \nStaff and since 2007, has been working as Head of Staff at National Cancer Center, Tokyo, Japan. Board certifications are Radiological Society of North America, Japan Radiological Society, Japan Association of Breast Cancer Screening, Japanese Association for \nCancer Detection and Diagnosis, The Japanese Society of Nuclear Medicine, and Certified Radiation Protection Supervisor, 1st Grade.",institutionString:null,institution:{name:"National Cancer Center",institutionURL:null,country:{name:"Korea, South"}}},{id:"200712",title:"Dr.",name:"Ryusuke",surname:"Murakami",slug:"ryusuke-murakami",fullName:"Ryusuke Murakami",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Nippon Medical School",institutionURL:null,country:{name:"Japan"}}},{id:"201368",title:"Dr.",name:"Hitomi",surname:"Tani",slug:"hitomi-tani",fullName:"Hitomi Tani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"201369",title:"Prof.",name:"Shinichiro",surname:"Kumita",slug:"shinichiro-kumita",fullName:"Shinichiro Kumita",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"201936",title:"Mr.",name:"Alexander",surname:"Karpov",slug:"alexander-karpov",fullName:"Alexander Karpov",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"206537",title:"Prof.",name:"Hu",surname:"Peng",slug:"hu-peng",fullName:"Hu Peng",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"206538",title:"Prof.",name:"Jianhua",surname:"Ma",slug:"jianhua-ma",fullName:"Jianhua Ma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"257388",title:"Distinguished Prof.",name:"Lulu",surname:"Wang",slug:"lulu-wang",fullName:"Lulu Wang",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",biography:"Lulu Wang is a Distinguished Professor of Biomedical Engineering, Shenzhen Technology University, China. Dr. Wang is a member of the American Society of Mechanical Engineers (ASME), Institute of Electrical and Electronics Engineers (IEEE), American Association for the Advancement of Science (AAAS), Physiological Society of New Zealand (PSNZ), and Institution of Professional Engineers New Zealand (IPENZ). Her research interests include medical devices, electromagnetic sensing and imaging, and computational mechanics. Over the past five years, Dr. Wang has authored more than seventy peer-reviewed publications, two ASME books, seven book chapters, and ten issued patents. She is an active reviewer of numerous journals, books, and conferences. She has edited four books and three special issues of international journals. She has received multiple national and international awards from various professional societies and organizations. She is an active organizer of several international conferences, including the ASME International Mechanical Engineering Congress & Exposition and the International Conference on Computational & Experimental Engineering Sciences. She has been selected as the World’s Top 2% Scientists 2021 (by Stanford University).",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"380898",title:"Dr.",name:"Andrey",surname:"Kolobanov",slug:"andrey-kolobanov",fullName:"Andrey Kolobanov",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"our-story",title:"Our story",intro:"
The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.
",metaTitle:"Our story",metaDescription:"The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.",metaKeywords:null,canonicalURL:"/page/our-story",contentRaw:'[{"type":"htmlEditorComponent","content":"
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\\n\\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\\n\\n
The IntechOpen timeline
\\n\\n
2004
\\n\\n
\\n\\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\\n\\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\\n
\\n\\n
2005
\\n\\n
\\n\\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\\n
\\n\\n
2006
\\n\\n
\\n\\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\\n
\\n\\n
2008
\\n\\n
\\n\\t
Downloads milestone: 200,000 downloads reached
\\n
\\n\\n
2009
\\n\\n
\\n\\t
Publishing milestone: the first 100 Open Access STM books are published
\\n
\\n\\n
2010
\\n\\n
\\n\\t
Downloads milestone: one million downloads reached
\\n\\t
IntechOpen expands its book publishing into a new field: medicine.
\\n
\\n\\n
2011
\\n\\n
\\n\\t
Publishing milestone: More than five million downloads reached
\\n\\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\\n\\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\\n\\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\\n
\\n\\n
2012
\\n\\n
\\n\\t
Publishing milestone: 10 million downloads reached
\\n\\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\\n
\\n\\n
2013
\\n\\n
\\n\\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\\n
\\n\\n
2014
\\n\\n
\\n\\t
IntechOpen turns 10, with more than 30 million downloads to date.
\\n\\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\\n
\\n\\n
2015
\\n\\n
\\n\\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\\n\\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\\n\\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\\n\\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\\n
\\n\\n
2016
\\n\\n
\\n\\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\\n
\\n\\n
2017
\\n\\n
\\n\\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\\n\\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\n\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\n\n
The IntechOpen timeline
\n\n
2004
\n\n
\n\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\n\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\n
\n\n
2005
\n\n
\n\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\n
\n\n
2006
\n\n
\n\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\n
\n\n
2008
\n\n
\n\t
Downloads milestone: 200,000 downloads reached
\n
\n\n
2009
\n\n
\n\t
Publishing milestone: the first 100 Open Access STM books are published
\n
\n\n
2010
\n\n
\n\t
Downloads milestone: one million downloads reached
\n\t
IntechOpen expands its book publishing into a new field: medicine.
\n
\n\n
2011
\n\n
\n\t
Publishing milestone: More than five million downloads reached
\n\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\n\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\n\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\n
\n\n
2012
\n\n
\n\t
Publishing milestone: 10 million downloads reached
\n\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\n
\n\n
2013
\n\n
\n\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\n
\n\n
2014
\n\n
\n\t
IntechOpen turns 10, with more than 30 million downloads to date.
\n\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\n
\n\n
2015
\n\n
\n\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\n\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\n\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\n\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\n
\n\n
2016
\n\n
\n\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\n
\n\n
2017
\n\n
\n\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\n\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
\n
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He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. 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\r\n\tIf we aim to prosper as a society and as a species, there is no alternative to sustainability-oriented development and growth. Sustainable development is no longer a choice but a necessity for us all. Ecosystems and preserving ecosystem services and inclusive urban development present promising solutions to environmental problems. Contextually, the emphasis on studying these fields will enable us to identify and define the critical factors for territorial success in the upcoming decades to be considered by the main-actors, decision and policy makers, technicians, and public in general.
\r\n
\r\n\tHolistic urban planning and environmental management are therefore crucial spheres that will define sustainable trajectories for our urbanizing planet. This urban and environmental planning topic aims to attract contributions that address sustainable urban development challenges and solutions, including integrated urban water management, planning for the urban circular economy, monitoring of risks, contingency planning and response to disasters, among several other challenges and solutions.
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