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Philippe Gillery France
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Magdalena Krintus Poland
Giuseppe Lippi Italy
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BC: Articoli scritti da G. Lippi

Impatto epidemiologico della patologia ischemica del miocardio in Italia
Epidemiologic burden of ischemic heart disease in Italy
G. Lippi  |  C. Mattiuzzi  |  C. Bovo  |  G. Cervellin  | 
<p>Background: this article provides an updated overview on the current epidemiologic burden of ischemic heart disease (IHD) in Italy.<br />Methods: an electronic search was carried out in the Global Health Data Exchange (GHDx) registry, using the keyword &ldquo;ischemic heart disease&rdquo;, for retrieving recent information (year 2017) on incidence, prevalence, health loss (expressed as disability-adjusted life year, DALYs) and mortality of IHD in Italy.<br />Results: the cumulative incidence, prevalence and mortality of IHD in Italy are 0.38%, 3.47% and 0.16% respectively, whilst the impact on health loss is 1.11 million DALYs (6.73% of total DALYs). Incidence, prevalence and DALYs are higher in men than in women, whilst mortality is only marginally higher in males. Overall, IHD is the first cause of death in Italy (15.5% of all deaths). During the last three decades the incidence has constantly increased (+30%), whilst DALYs have declined in both sexes by ~30%. Mortality for IHD steadily decreased in men (-13%), whilst it remained almost unchanged in women. The curve of incidence of IHD in Italy peaks between 60-84 years in men and between 75-94 years in women. The mortality curve of IHD in Italy peaks in both sexes between 85-94 years. Hypertension, hypercholesterolemia and diabetes are the leading risk factors for IHD in Italy.<br />Conclusions: IHD still poses a substantial clinical, social and economic burden in Italy.</p>
Biochimica Clinica ; 44(2) S048-S053
Contributi Scientifici - Scientific Papers
Raccomandazioni per la rilevazione e la gestione dei campioni non idonei nei laboratori clinici
Recommendations for the detection and management of unsuitable samples in clinical laboratories
<p>A large body of evidence supports that quality improvement efforts tailored to the analytical phase only, are less likely to generate further clinical and economical progresses. Actually, most diagnostic errors made within the laboratory diagnostics emerge in the extra-analytical domains of testing, especially within the preanalytical phase. It is now clear that the underlying causes are most frequently due to system errors or to the implementation of poorly standardized procedures for collection, handling, transportation, preparation and storage of biospecimens. Some of these problems could generate a number of issues related to the quality of clinical samples, ending up with the reception by the laboratory of unsuitable samples. The identification and the management of unsuitable samples represent thus unavoidable practices in clinical laboratories to guarantee the quality of test results throughout the total testing process. Due to the ongoing evolution of the in vitro diagnostic market and the availability of new evidence, this paper provides a revision of the national recommendations issued by the Italian Society of Clinical Biochemistry and Clinical Molecular Biology in 2007 for detection and practical management of unsuitable specimens in clinical laboratories.</p>
Biochimica Clinica ; 44(2) 180-193
Documenti SIBioC - SIBioC Documents
Variabilità biologica dei parametri dell’esame emocromocitometrico in soggetti sani
Biological variation estimates of complete blood count parameters in healthy subjects
<p>Background: the complete blood count (CBC) is the test more frequently requested in clinical practice. Therefore, estimating the biological variation (BV) of CBC parameters is essential for assessing the analytical performance of hematological analyzers and for enabling accurate data interpretation and appropriate clinical management. This study was aimed to define BV estimates and reference change value (RCV) of CBC parameters.<br />Methods: the study population consisted of 21 healthy volunteers, who had BV of CBC parameters assessed with Sysmex XN. The study protocol, the analytical measurements and the statistical analysis were carried out according to current recommendations of the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM).<br />Results: Within-subject BV ranged between 0,3% for mean cell hemoglobin (MCH) and 19,7% for immature granulocytes (IG), whilst between-subjects BVs ranged between 0,9% for mean corpuscolar haemoglobin concentration (MCHC) and 66,6% for microcytic red blood cells (Micro-R). The RCV ranged between 2,3% for MCH and 73,5% for IG.<br />Conclusion: This study has allowed the estimation of BV of many CBC parameters, some of which have not been currently explored, thus leading the way to use RCV calculated according to time of monitoring and/or differentiated by sex.</p>
Biochimica Clinica ; 43(4) 384-393
Contributi Scientifici - Scientific Papers
Interferenza da biotina negli immunodosaggi: raccomandazioni del Gruppo di Studio SIBioC sulla Variabilità Extra-Analitica (SIBioC-VEA)
Biotin interference in immunoassays: recommendations of the SIBioC Working Group on Extra-AnalyticalVariability (WG-VEA).
<p><span style="background-color:rgb(255, 255, 255); color:rgb(51, 51, 51); font-family:sans-serif,arial,verdana,trebuchet ms; font-size:13px">Biotin is a water-soluble vitamin, which participates to a vast array of metabolic pathwaysinvolving fatty acids, carbohydrates and amino acids metabolism. This vitamin is also capable to form high-affinitybonds with various molecules, including streptavidin and avidin, which are essential components of manyimmunoassays based on the principle of biotin-streptavidin or biotin-avidin binding. In patients assuming high dosesof biotin, therefore, some competitive and non-competitive immunoassays may exhibit falsely increased and falselydecreased test results, respectively, with magnitude of interference depending on biotin concentration in the testsample and on specific vulnerability of the immunoassay. With the aim to provide some expert guidance foridentifying, preventing and managing biotin interference in clinical laboratory practice, this document contains a seriesof consensus recommendations endorsed by the Working Group on Extra-Analytical Variability of the Italian Societyof Clinical Chemistry and Clinical Molecular Biology (SIBioC). Briefly, the most important recommendationsencompass local evaluation of possible biotin interference, routine history taking on biotin intake for both inpatientsand outpatients, informing clinicians on potentially biotin-sensitive immunoassays, sample retesting 24-48 hours afterthe last biotin administration, along with possible consideration to add a note in the laboratory report highlighting themethods more vulnerable to biotin interference. Routine biotin measurement in all samples is currently discouraged.</span></p>
Biochimica Clinica ; 43(3) 327-331
La diagnostica di laboratorio nella sindrome da apparente eccesso di mineralcorticoidi
The laboratory diagnosis of apparent mineralocorticoid excess (AME)
<p>The apparent mineralocorticoid excess(AME) is a rare genetic disorder caused by impaired activity of the enzyme 11&beta;-hydroxysteroid dehydrogenase type2 (11&beta;HSD2). This abnormality is associated with cortisol excess and abnormal activation of mineralocorticoidreceptor, which is usually only activated by aldosterone. More than 50 known mutations have been associated withAME; whilst some epigenetic modifications may also be involved. AME causes severe hypertension and is hencetraditionally diagnosed during the first years of life. Deficit of 11&beta;HSD2 also occur in other physiopathologicalconditions like pre-eclampsia, sodium-sensitive hypertension and kidney or hepatic impairment. The biochemicaldiagnosis is conventionally made by quantifying tetrahydroxylated metabolites of cortisol (THF and allo-THF) andcortisone (THE) expressed as THF+allo-THF/THE ratio and using home-made Gas Chromatography-MassSpectrometry methods. Nevertheless, some recent studies showed more accurate characterization of 11&beta;HSD2deficit by measuring the urinary free cortisol/cortisone ratio with Liquid Chromatography-Tandem Mass Spectrometry.A final consensus on the preferred method to diagnose AME has not been reached so far, and more studies areneeded for better defining sensitivity and specificity of these tests in some different physiopathological conditionsassociated with 11&beta;HSD2 impairment.</p>
Biochimica Clinica ; 43(3) 264-268
Rassegne - Reviews
Medicina di Laboratorio e Medicina d’Urgenza: il connubio continua
Laboratory medicine and emergency medicine: a perpetual relationship.
<p>The essential goals that laboratorymedicine shall pursue to adequately fulfill clinical needs can be summarized in delivering high quality information,availability of clinically usable tests and turnaround time. The governance of urgent laboratory testing encompassesa harmonious integration of clinical needs and laboratory organization. Clinical laboratories shall hence be morefocused on the pre-preanalytical phase, be involved in proactive efforts for standardizing pre-analytical and analyticalprocedures, optimize the post-analytical and post-post-analytical phases, thus providing a complete information andallowing the achievement of favorable outcomes. Throughout this ample and multifaceted process, the strictcooperation between laboratory professionals and emergency physicians is pivotal. As rationale follow-up of thecollective article published concomitantly with the first joint Academy of Emergency Medicine and Care (AcEMC) -Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) meeting, this new collective paperaims to summarize the topics discussed during the second joint event &ldquo;Laboratory Medicine and EmergencyMedicine: a resumed link&rdquo;, specifically including the governance of urgent tests, acid-base disorders, venousthromboembolism, acute heart failure, trauma, acute intoxications, viral diseases and other emerging infections.</p>
Biochimica Clinica ; 43(3) 296-304
Documenti - DOCUMENTS
Ridurre l’inappropriatezza in medicina di laboratorio: come, quando e perchè
Improving appropriateness in laboratory medicine: how, when and why
<p><span style="color:rgb(33, 29, 30); font-size:9pt">The issue of the appropriateness in laboratory medicine has been discussed from several years in association to theparallel onset of two aspects: 1) the significant increase in tests demand and utilization, thanks to the developmentof laboratory automation and information laboratory systems (LIS), that allow to provide timely and reliable results toclinicians; 2) the opportunity, thanks to new pathophysiological knowledge and new technologies to introduce newand more sophisticated tests in clinical practice, providing a relevant support to the clinician in the management ofpatients, according to the improved vision of personalized medicine. As a consequence, the potentialinappropriateness in test utilization and the need to manage demand and to reduce the redundant testing havereceived increasing concern. Several papers, in the recent literature, demonstrated that the inappropriateness inlaboratory test utilization may represent a potential source of errors, and interesting strategies have been proposedand progressively adopted in order to limit this problematic outcome. An essential issue is to assure appropriatenessnot only in test request, but in all steps of the testing cycle. In particular, some of the more relevant issues has beenlinked to: rationalization of laboratory test ordering prescription, thanks to development of a computerized clinicaldecision support systems; implementation of the reflexing tests rule; definition of the minimum retesting intervalaccording to the clinical and pathophysiological criteria; timely revision of the available panel tests in order to deletethose considered obsolete from clinical and analytical point-of-view and, finally, improving the education in demandmanagement. The &ldquo;clinical laboratory stewardship&rdquo; seems to be the new and shared strategy, that guarantees notonly the appropriate utilization and interpretation of laboratory tests improving efficacy and providing efficiency but,more importantly, the future of the discipline and the role of laboratory professionals in the context of new and morecomplicated clinical and economical scenarios.</span></p>
Biochimica Clinica ; 43(3) 305-312
Documenti SIBioC - SIBioC Documents
Telomere shortening and PCDH10 promoter methylation in colorectal cancermucosae
<p>Background: telomerase activity and telomere length (TL) have important implications in several human diseases.Telomere shortening is associated with colorectal carcinogenesis. Recent studies also showed that protocadherin 10(PCDH10) plays a critical role in cancer cell growth, by negatively regulating telomerase activity. PCDH10isfrequently downregulated by promoter DNA methylation. The aim of this study was to investigate whether PCDH10promoter methylation was associated with TL in colorectal cancer (CRC).<br />Methods: DNA was extracted from 35 CRC and 35 adjacent normal tissues with Gentra Purgene Kit (Qiagen, Hilden,Germany). A quantitative methylation-specific PCR (MSP) based method was used to analyze a selected CpG site inPCDH10promoter. TL was evaluated with qPCR and expressed as telomere to single copy gene (T/S) ratio.Differences were assessed with Mann-Whitney test or Wilcoxon signed-ranks test when appropriate, whilstcorrelation analyses were performed with Spearman&rsquo;s test. Diagnostic performance was calculated with receiveroperating characteristics (ROC) curve analysis. The level of statistical significance was set at p &lt;0.05.<br />Results: we found that TL was significantly lower in CRC than in adjacent non-cancerous tissues (p=0.0005). Thearea under the ROC curve (AUC) for TL was 0.759 (95% Confidence Interval: 0.643-0.875, p=0.0002). AberrantPCDH10promoter methylation was detected in 100% of CRC tissues but in none of paired non-cancerous tissues.The median methylation rate in CRC tissues was 55.7% (range: 6.1-97.8%). TL was negatively correlated withPCDH10promoter methylation (r=-0.42, p=0.0002).<br />Conclusions: these results suggest a pivotal role of telomere shortening and PCDH10methylation in CRC tissues.TL may be seen as a potential biomarker in CRC diagnostics.</p>
Biochimica Clinica ; 43(3) 278-283
Contributi Scientifici - Scientific Papers
Medicina di laboratorio e Medicina d’urgenza: un connubio indissolubile
Laboratory Medicine and Emergency Medicine: an essential partnership
<p>Laboratory Medicine and Emergency Medicine: an essential partnership. A better understanding of the pathophysiological bases of many pathologies, along with the considerable technological advances occurred over last few years, have allowed to broaden number and complexity of in vitro diagnostic tests. The emergency department is the clinical setting with the highest risk of forensic disputes, and this explains the inclination that many emergency physicians have towards defensive medicine. Disproportionate request of laboratory tests, with poor awareness on the impact of inappropriateness, is one of the leading negative aftermath of this attitude. The predictable consequences are economic, but also encompass the risk of generating direct damage to the patients, especially in the presence of false positive test results. Since diagnostic appropriateness represents an essential element for patient safety and for sustainability of the National Healthcare System, the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) and the Academy of Emergency Medicine and Care (AcEMC) have organized a joint meeting entitled &quot;Laboratory Medicine and Emergency Medicine: an essential partnership&quot;, of which this document is a summary. The issues that have been discussed represent major diagnostic dilemmas faced by emergency physicians, and for which the contribution of laboratory medicine may be decisive. These include acute systemic infections, acute abdominal pain, acute chest pain, head injury and acute bleeding. Since timely transmission of test results is an additional critical element for the clinical decision making in emergency settings, the document will also include considerations on sample transportation from the emergency room to the laboratory.</p>
Biochimica Clinica ; 42(4) 335-342
Documenti - Documents
Indagine conoscitiva congiunta SIBioC-Medicina di Laboratorio e Associazione Italiana Pneumologi Ospedalieri (AIPO) relativa alla gestione del processo diagnostico del liquido pleurico
Results of a survey produced by the Italian Society of Clinical Biochemestry (SIBioC) and the Italian Association of Hospital Pneumologists (AIPO) concerning pleural fluid analysis
<p>The aim of this paper is to present the preliminary results of a joint project by SIBioC-AIPO working group on &ldquo;Body cavities fluids&rdquo;. The main purpose of the working group is to achieve a harmonized and shared diagnostic pathway related to pleural fluid (PF) analysis. The multistep project begins with a state of the art analysis. A survey, sent to both laboratory medicine personnel and pneumologists, was conducted between October and December 2016. The questionnaire (21 questions) was made available through the web-based SurveyMonkey platform. Overall, 408 replies were collected, 40.4% from laboratory medicine specialists, 3.2% from laboratory technicians, 49.3% from pneumologists and 7.1% from professionals with non-specified qualification. Regarding the pre-analytical phase, the most critical issue resulted to be the clinical query, due to the lack of structured communication between clinicians and laboratory personnel. While over 76% of laboratory professionals stated that the working diagnosis was unavailable, 87% of pneumologists affirmed that the clinical question had been forwarded to the laboratory. An important issue was the widespread use of inappropriate containers for PF collection (60% of inappropriate tubes). Regarding the panel of tests, a satisfactory agreement was reached on the need to perform macroscopic analysis and cytometric evaluation, along with the assessment of pH, glucose, total proteins, lactate dehydrogenase and the respective ratios between PF and serum concentrations. As expected, the availability of verified or validated analytical methods, notably pH analysis, has emerged as a critical point. The layout of the laboratory report also needs improvements and better harmonization. Despite the many critical issues emerged from this survey, a positive feedback was reflected by a notable general interest on PF analysis, leading thus the way to produce a joint consensus document involving clinicians and laboratory personnel, as suggested by more than 30% of responders.</p>
Biochimica Clinica ; 42(2) 119-130
Contributi Scientifici - Scientific papers
Meccanismi epigenetici: l’esempio del Diabete Mellito tipo 1
Epigenetics in Type 1 Diabetes Mellitus
M. Montagnana  |  G. Lippi  |  E. Danese  | 
<p>Type 1 diabetes mellitus (T1DM) is a chronic autoimmune illness characterized by insufficient production of insulin by pancreatic beta cells. This condition occurs by environmental disruption (mostly supported by viral infections or nutritional components) of immune tolerance in genetically susceptible individuals. The lack of concordance in monozygotic twins for common diseases as T1DM has led to hypothesize that epigenetics may have a pivotal role in the pathogenesis of this condition, by modulating the relationship between the genotype and the phenotype. Epigenetics is commonly defined as the regulation of gene expression through chemical changes including DNA methylation or histone modulation of noncoding RNAs, without directly involving mutational changes in DNA. Epigenetics has recently contributed to amplify our understanding of the mechanisms underlying different pathological conditions for which causes other than genetic mutations and environmental factors are involved. Epigenetic modification in T1DM may hence mediate the environmental influence on expression of genes involved in the pathogenesis of disease. Therefore, this review is focused on describing the leading epigenetic mechanisms participating to the pathogenesis and progression of T1DM, and discussing the diagnostic or prognostic role of some potentially useful epigenetic biomarkers.</p>
Biochimica Clinica ; 42(2) 097-102
Rassegne - Reviews
Procalcitonina in Terapia Intensiva: più certezze che dubbi
Procalcitonin in intensive care unit: more confidence than hesitation
G. Lippi  |  C. Mattiuzzi  | 
Biochimica Clinica ; 42(2) 180-182
Lettere all'Editore - Letters to the Editor
Raccomandazioni per l’identificazione e la gestione dei risultati critici nei laboratori clinici
Recommendations for the detection and management of critical results in clinical laboratories
<p>Critical results, (also known as panic or alarm results) identify a laboratory test result associated with a serious risk for the patient&rsquo;s health, requiring immediate communication to the physician to establish appropriate therapeutic interventions. The adoption of an efficient procedure for the communication of critical values/results is crucial for clinical, ethical, organizational reasons, because it is a requirement for laboratory accreditiation and because of potential legal consequences related to the lack of notification of harmful laboratory results. In 2008, the Italian Society of Clinical Biochemistry and Laboratory Medicine (SIBioC) published its first consensus-based recommendation for the detection and management of critical values in clinical laboratories, with the aim to improve the implementation of standardized and universally accepted procedures, promoting an essential policy toward rational and efficient solutions to this issue. These new recommendations represent a complete review of the first document. Using the same consensus conference method between experts of scientific societies, the main aspects of clinical risk, patient safety and legal liability of health care workers were re-considered. The SIBioC and the Italian Society of Laboratory Medicine (SIPMeL), Intersociety Study Group on Standardization of extra-analytical variability of laboratory results, together with the Italian Society of Ergonomics and Human Factors (SIE) collaboration, issued the present join document.</p>
Biochimica Clinica ; 42(2) 167-179
Documenti SIBioC - SIBioC Documents
Documento di consenso SIBioC-Medicina di Laboratorio e Academy of Emergency Medicine and Care (AcEMC) sull’utilizzo in Pronto Soccorso dei biomarcatori per la diagnosi di sepsi batterica
Biomarkers for diagnosing sepsis in the emergency department: a consensus document by SIBioCMedicina di Laboratorio and the Academy of Emergency Medicine and Care
<p>This article is drafted as a consensus document involving eight members of the Italian Society of Clinical Biochemistry and Laboratory Medicine (SIBioC) and eight members of the Academy of Emergency Medicine and Care (AcEMC), to whom a questionnaire was submitted for obtaining opinions on some recommendations about the use of biomarkers for diagnosing sepsis and managing antibiotic therapy in the emergency department. These recommendations were drafted following the National Guidelines Program (PNLG). According to the cumulative consent, three &quot;A&quot; recommendations (strongly recommended indication) emerged, which include biomarker availability (always available on prescription), clinical use (always interpreted in according to clinical data) and timing of the request based on half-life of the analyte. Recommendations of type &quot;B&quot; (indications carefully considered) included a general agreement about the clinical usefulness of sepsis biomarkers, the combination of procalcitonin (PCT) and Creactive protein (CRP), the possibility to be free on prescription to the laboratory, the use of cut-offs favoring a high negative predictive value, the use of more analytically sensitive assays and the possibility of using PCT for monitoring antibiotic therapy, with timing of ordering defined according to the metabolism of the analyte. As regards the specific biomarkers, a similar &ldquo;B&rdquo; consensus has been reached for measuring both PCT and CRP, and for measuring lactic acid. The measurement of other biomarkers is discouraged except for presepsin, for which there is still substantial uncertainty in favor or against.</p>
Biochimica Clinica ; 42(1) 62-73
Documenti SIBioC - SIBioC Documents
Esami di laboratorio in Pronto Soccorso: una proposta di consenso SIBioC - Medicina di Laboratorio e Academy of Emergency Medicine and Care
Laboratory tests in the Emergency Department: a consensus document by SIBioC-Medicina di Laboratorio and the Academy of Emergency Medicine and Care
<p>Laboratory diagnostics in the emergency setting encompasses the identification of appropriate testing according to specific acute conditions. Since the pathway of ordering tests in the Italian Emergency Departments (EDs) is rather heterogeneous, SIBioC-Medicina di Laboratorio and the Academy of Emergency Medicine and Care designed a survey aimed to generate consensus pertaining to appropriate laboratory tests in most frequent acute conditions. A questionnaire including a panel of laboratory tests was administered to 8 representative members of each of the two societies, who were asked to provide a score between 1 and 3 for the various tests, where a score of 1 entailed &ldquo;highly recommended&rdquo;, 2 &ldquo;recommended in specific conditions&rdquo; and 3 identified &ldquo;highly discouraged&rdquo; tests. The results of the questionnaire are shown as mean (&plusmn;SD) of individual responses, thus allowing to define a scale of priority comprised between &ldquo;highly recommended&rdquo; and &ldquo;highly discouraged&rdquo;. Overall, 24 tests were classified as &ldquo;highly recommended&rdquo;, whereas 6 were &ldquo;highly discouraged&rdquo;. The remaining 16 tests were classified as &ldquo;somehow recommended&rdquo; or &ldquo;somehow discouraged&rdquo;. In the expectations of the two societies, this document may represent a first step towards harmonizing the laboratory test ordering in Italian EDs.</p>
Biochimica Clinica ; 41(2) 183-188
Documenti SIBioC - SIBioC Documents
Indagine conoscitiva su matrice biologica e gestione della fase preanalitica nei laboratori clinici
Indagine conoscitiva su matrice biologica e gestione della fase preanalitica nei laboratori clinici
<p>The vast majority of biochemistry tests is traditionally performed using either serum or heparinized plasma. Since little information is available on organization of clinical chemistry areas and type of biological samples used for this type of testing, the SIBioC Study Group on Extra-analytical variability planned a survey to be delivered to the members of the society. The questionnaire, consisting of 10 questions, was delivered by two newsletters and published on the SIBioC website for one month. Overall, 229 replies were collected from ~3000 society members. The most relevant aspect emerged from the survey was that serum not only was the most common biological matrix used for clinical chemistry tests (82% of responders), but it was also regarded as the ideal biological matrix (76% of responders). In 80% of cases, clinical chemistry testing was performed using blood collected in tubes containing a separator. Unlike ordinary testing, urgent analyses were performed using serum only in 58% of cases. The use of blood tubes with separator was also more frequent for urgent chemistry testing (64% of responders). A physical integration between clinical chemistry instruments was reported in approximately half of cases, whereas integration with preanalytical modules was reported to be slightly lower (45% of responders). The availability to change the biological matrix by the majority of responders demonstrates a substantial awareness that a major degree of harmonization should be pursued in the preanalytical phase.</p>
Biochimica Clinica ; 41(2) 142-147
Contributi scientifici - Scientific papers
miR-199a and miR-125b expression levels in serum of women affected by epithelial ovarian cancer
<p>Recent studies show that microRNA (miRNAs) are involved in cancer by regulating cell proliferation, apoptosis and angiogenesis. Accordingly, their deregulation could contribute to cancer development and progression. It has been demonstrated that in ovarian tissue the over-expression of miR-199a and miR-125b inhibits tumor angiogenesis, a fundamental process for cancer development and growth. Aims of our study were to investigate the expression levels of miR-199a and miR-125b in serum of patients with ovarian cancer (OC) and to evaluate the correlation between miRNAs expression and traditional biomarkers [CA125 and human epididymis protein 4 (HE4)]. 32 patients with epithelial OC (54&plusmn;14 years old) and 31 healthy controls (55&plusmn;17 years old) were enrolled. Serum samples were collected prior to definitive surgical treatment and RNA extraction was performed by using the miRNeasy Serum/Plasma kit (Qiagen GmbH). miR-199a and miR-125b expression was determined by quantitative real timepolymerase chain reaction (TaqMan MicroRNA Assay, Applied Biosystems). The expression levels of miRNAs were normalized to miR-16 and calculated utilizing the 2-&Delta;Ct method. Serum levels of miR-199a and miR-125b were significantly higher in OC patients compared to controls (P=0.007 and P=0.002, respectively). A marginally statistically significant correlation was found between miR-199a and miR-125b expression levels (r=0.38, P=0.03). The ROC curve analysis of the diagnostic performance between healthy controls and OC patients revealed that HE4 had a significantly higher area under the curve (AUC=0.90) when compared to CA125 (AUC=0.85), miR-199a (AUC=0.70) and miR-125b (AUC=0.67). Anyway, the determination of circulating miRNAs may be relevant, since their expression is known to be aberrant in cancer, having potential ability to monitor tumor dynamics.</p>
Biochimica Clinica ; 40(4) 328-333
Contributi scientifici - Scientific Papers
Verifica locale dei sistemi di prelievo nei laboratori clinici: adattamento delle linee guida EFLM
Blood collection systems in clinical laboratories: local adaptation of the EFLM guidelines
<p>The importance of the process of purchasing or changing blood collection devices is often overlooked. This is likely attributable to many factors such as the limited knowledge that policymakers, healthcare administrators and also laboratory managers have on the significance of preanalytical quality, but also to the lack of validated criteria for analyzing the quality of blood collection devices. Since a gap remains to be filled between companies&rsquo; and laboratory&rsquo;s validation, the EFLM Working Group on Preanalytical Phase (WG-PRE) has published a comprehensive document, which contains essential prerequisites and technical issues (e.g., physical imperfections, defects of functioning, safety deficiencies) to support local clinical laboratories for the development of tenders for blood tubes and for the validation of new materials ahead of local routine use. This consensus document is a national adaptation of these guidelines.</p>
Biochimica Clinica ; 40(4) 347-352
Documenti SIBioC - SIBioC Documents
Intervalli di riferimento dell’esame emocromocitometrico nel sangue di cordone ombelicale
Reference intervals for cell counts of umbilical cord blood
F. Dima  |  M. Montagnana  |  R. Raffaelli  |  S. Cascella  |  C. Bovo  |  M. Franchi  |  G. Lippi  | 
<p>The umbilical cord blood is useful for assessing the&nbsp;health status in newborns. A limited number of studies evaluated the reference values of peripheral blood cell count&nbsp;and little information is available on the number of stem cells in umbilical cord blood. This study aimed to define&nbsp;reference intervals for hematological parameters in umbilical cord blood. 257 umbilical cord blood samples were&nbsp;obtained from apparently healthy infants with gestational age &gt;37 weeks, uncomplicated pregnancy, birth weight&nbsp;&gt;2500 g and umbilical arterial pH &gt;7.0. The analysis was performed within 3 h from collection using the hematology&nbsp;analyzer Sysmex XN-1000. Reference values were derived with a non-parametric approach, by following the CLSI&nbsp;document EP28&ndash;A3c. A statistically significant difference between genders was observed for erythrocytes,&nbsp;hemoglobin, hematocrit and red blood cell distribution width, these parameters being significantly higher in males&nbsp;than in females. Results from this study may be seen as a useful guide for neonatologists to evaluate the newborn&nbsp;status and for hematologists to evaluate the quality of collected blood.</p>
Biochimica Clinica ; 40(3) 204-207
Contributi scientifici - Scientific Papers
Valutazione analitica della misura di nuovi parametri emocitometrici su analizzatore Sysmex XN-9000
Assessment of the analytical performance of novel parameters of automated blood count on Sysmex XN-9000
<p>Recent technological advancements in laboratory hematology have promoted the introduction of many innovative parameters, which have the potential to enhance the clinical efficiency of this diagnostic area. This study aimed to&nbsp;assess the analytical performance of some of these new parameters available on Sysmex XN-9000 according to the&nbsp;International Council for Standardization in Haematology (ICSH) guidelines. Our evaluation included the assessment&nbsp;of imprecision (both intra- and inter-assay), carryover, sample stability and comparison with optical microscopy. The&nbsp;new red blood cell and platelet parameters displayed CV comprised between 0.7% and 34.6%. The new leukocyte&nbsp;parameters immature granulocyte (IG), hight fluorescence cell and cell population data (CPD) were characterized by&nbsp;CV ranging from 1% to 24%. Carryover was negligible for all parameters. Samples stability showed different trends&nbsp;for the different parameters, especially for CPD, depending on temperature and time of testing. The comparison of&nbsp;IG and nucleated red blood cell (NRBC) enumeration determined with Sysmex XN-9000 and optical microscopy&nbsp;yielded Pearson&rsquo;s correlation coefficients comprised between 0.82 and 0.99. The absolute bias was 0.83% and -0.06% for IG and NRBC, respectively. The results of this evaluation show that the innovative parameters available on&nbsp;Sysmex XN-9000 display, with some exceptions, acceptable performance, in line with data obtained with other&nbsp;analyzers. The results of sample stability studies are helpful to identify the best storage conditions for these&nbsp;parameters.</p>
Biochimica Clinica ; 40(3) 217-224
Contributi scientifici - Scientific Papers
L'assassino occulto
G. Lippi  | 
Biochimica Clinica ; 40(2) 168-169
Recensioni - Book reviews
A multicentre observational study evaluating the effectiveness of a phlebotomy check-list in reducing preanalytical errors
<p>Several preanalytical errors are attributable to inappropriate or poorly standardized activities during the venous blood&nbsp;collection. We designed a multicenter observational study to establish whether the implementation of a phlebotomy&nbsp;check-list in 7 phlebotomy centers and 4 emergency departments is effective in reducing the rate of preanalytical&nbsp;errors related to the blood drawing. The investigation was divided in two 3-month periods during which 5 common&nbsp;preanalytical errors were systematically recorded. After the introduction of the phlebotomy check-list, the rate of&nbsp;preanalytical errors was significantly decreased in phlebotomy centers (0.04% vs. 0.05%, P=0.001), but remained&nbsp;unchanged in emergency departments (0.83% vs. 0.82%, P=0.84). A significant decrease was achieved for sample&nbsp;identification errors and clotted specimens in phlebotomy centers and emergency departments, whereas a significant<br />reduction in hemolysis was noticed only in phlebotomy centers. The rate of inappropriate filling and wrong containers&nbsp;remained unchanged. The results obtained in this study show that the introduction of a phlebotomy check-list may&nbsp;help in reducing preanalytical errors related to misidentification and undue clotting.</p>
Biochimica Clinica ; 39(6) 559-562
Contributi scientifici - Scientific Papers
Armonizzazione in Medicina di Laboratorio
Harmonization in Laboratory Medicine
Biochimica Clinica ; 39(6) 546-547
Editoriale - Editorial
Indagine sulla modalità di refertazione dell’esame D-dimero nei laboratori nazionali e indicazioni per una sua armonizzazione
A survey on D-dimer test reporting in Italian laboratories and some suggestions for its harmonization
G. Lippi  |  B. Morelli  |  A. Tripodi  | 
<p>D-dimer&nbsp;assessment represents a cornerstone in the diagnostic approach and therapeutic management of several thrombotic&nbsp;disorders, namely venous thromboembolism and disseminated intravascular coagulation. Nevertheless, this test is still&nbsp;plagued by an insufficient degree of analytical and post-analytical standardization. In particular, despite the existence&nbsp;of national guidelines, result reporting is quite heterogeneous. A specific on-line, 5-item questionnaire was&nbsp;disseminated to the SIBioC members to obtain a picture of the current national situation. As regards to the units, a&nbsp;modest prevalence (53%) of D-dimer unit (DDU) over fibrinogen equivalent unit (FEU) (47%) was found. The most&nbsp;widespread measurement unit was &ldquo;ng/mL&rdquo; (60%), followed by &ldquo;&mu;g/L&rdquo; (18%), &ldquo;mg/L&rdquo; (15%) and &ldquo;&mu;g/mL&rdquo; (6%). The vast&nbsp;majority of laboratories (90%) did not use an age-adjusted cut-off. The data distribution did not differ among different&nbsp;types of healthcare settings (i.e., general hospital, university hospital or private facilities). The use of at least 16 different&nbsp;unit approaches for D-dimer emerged from the survey is quite alarming and calls for a standardization, using a single&nbsp;result reporting as .</p>
Biochimica Clinica ; 39(6) 591-594
Contributi scientifici - Scientific Papers
Determinazione degli intervalli di riferimento dell’esame emocromocitometrico eseguito con analizzatore Sysmex XN 9000
Evaluation of reference intervals for complete blood count on Sysmex XN 9000
<p>We aimed to define reference&nbsp;intervals for complete blood count in 240 apparently healthy Italian adults (120 males and 120 females) using Sysmex&nbsp;XN 9000 platform, as recommended by international standards. The recruitment criteria for reference individuals were&nbsp;based on negative anamnesis and physiological serum concentrations of glucose, creatinine, transaminases, ferritin&nbsp;and C-reactive protein. The results were comparable to those previously generated on different European&nbsp;populations. Interesting results were found for some research parameters, for which limited information was available&nbsp;in Italian populations so far. With regard to reticulocyte-related parameters, a significant gender difference was found&nbsp;for reticulocyte hemoglobin, highly fluorescent reticulocyte fraction and delta-He, which represents the difference in&nbsp;hemoglobin content between reticulocytes and erythrocytes. The results also support the reference interval of&nbsp;immature platelet fraction observed in previous studies, except for the absolute value for which larger range and&nbsp;higher values were found. For leukocyte morphological and functional parameters, we were able to define reference&nbsp;intervals in the whole study population as well as in male and female subgroups, since gender-related differences&nbsp;were observed for some parameters.</p>
Biochimica Clinica ; 39(4) 256-263
Contributi scientifici - Scientific Papers
Identificazione casuale di atrofia gastrica severa con macrocitosi complicata da sindrome coronarica acuta
Casual identification of severe gastric atrophy with macrocytosis complicated by acute coronary syndrome
<p>Chronic atrophic gastritis (CAG) and gastric cancer are leading causes of morbidity and mortality worldwide. Serum&nbsp;pepsinogens have been used as biomarkers of gastric mucosa status, including gastric inflammation, so that they&nbsp;might be useful for detection of gastric atrophy or gastric neoplasm at an early stage. Serum pepsinogen 1 and&nbsp;pepsinogen 2 concentrations are known to increase in the presence of <em>Helicobacter pylori</em>-related non-atrophic chronic&nbsp;gastritis, and the eradication of this pathogen is associated with a significant decrease in their values. We describe here&nbsp;the case of an asymptomatic 60 years old man, with a casual serological diagnosis of severe gastric atrophy,&nbsp;macrocytosis and severe complications, culminating in an acute coronary syndrome. This case report raises some&nbsp;important considerations, such as the fact that CAG could not be correctly and early diagnosed and that it may be&nbsp;misleadingly regarded as a rare condition, whereas its prevalence is conversely largely underestimated. This may lead&nbsp;to severe complications that may include gastric malabsorption and vitamin B<sub>12</sub> deficiency, along with gastrointestinal,&nbsp;neurologic, psychiatric, cardiovascular, cerebral and peripheral vascular disorders.</p>
Biochimica Clinica ; 39(1) 068-072
Casi clinici - Case report
I laboratori clinici nell’emergenza dei focolai epidemici infettivi: Ebola e oltre
Clinical laboratories and infectious outbreak emergencies: Ebola and beyond
G. Lippi  |  C. Mattiuzzi  |  M. Plebani  | 
Biochimica Clinica ; 38(6) 604-606
Editoriale - Editorial
Automated screening of bacterial meningitis by cytofluorimetric analysis of cerebrospinal fluid: preliminary results
<p>This study was planned to assess the diagnostic performance of the automated urine particle analyzer Sysmex UF-1000i for the rapid screening of cerebrospinal fluid (CSF) in patients with suspected meningitis. Cytometric analyses&nbsp;with either optical microscopy (OM) or UF-1000i, along with assessment of glucose and protein in CSF, were performed&nbsp;on 101 consecutive CSF of patients with suspected meningitis. In 50 out of 101 samples, cultural analysis was also&nbsp;performed with different culture media. Four different diagnostic combination were developed, with different mix of the&nbsp;tested parameters. A high correlation was found between OM and UF-1000i (r=0.99; mean bias, -4.9/&mu;L). The&nbsp;diagnostic agreement was 0.90 in adults and 0.97 in children. The diagnostic agreement between CSF culture and&nbsp;bacterial count by UF-1000i was 0.98, with 1.00 sensitivity and 0.98 specificity. Results showed that the diagnostic&nbsp;combination based on CSF glucose and total proteins, cytometric analysis (leukocyte count &plusmn; neutrophilia) and&nbsp;bacterial count on UF1000i exhibited the best performance when compared with microbiological examination (area&nbsp;under ROC curve, 1.00). In conclusion, the results of this study show that the combination of two rapid clinical&nbsp;chemistry tests such as glucose and total proteins with UF-1000i analysis could represent a valid approach for&nbsp;supporting more complex analyses or even for replacing OM and CSF culture during stat examination and to achieve&nbsp;a quick detection of central nervous system infections.</p>
Biochimica Clinica ; 38(3) 208-212
Contributi scientifici - Scientific Papers
Proteina S100B ed enolasi neurone-specifica nella valutazione iniziale del trauma cranico lieve nell’adulto: pronte per il debutto nel mondo reale?
Protein S100B and neuron-specific enolase (NSE) for the initial evaluation of mild head trauma in adults: ready for prime time?
<p>Computerized tomography (CT) remains the best option for diagnosis of head trauma,&nbsp;although it carries several drawbacks. Among a large number of putative biomarkers proposed for initial evaluation&nbsp;of mild head trauma, protein S100B and NSE exhibit the best diagnostic performance. We performed a prospective&nbsp;study, where these biomarkers were assessed in 68 patients consecutively admitted to the Emergency Department&nbsp;(ED) with mild head trauma. The CT scan revealed brain lesions in 11 patients (16%). Concentrations of both&nbsp;biomarkers in serum were found to be more elevated in patients with positive CT than in those with negative scans.&nbsp;The area under the ROC curve (AUC) of protein S100B (0.89, 95% confidence interval: 0.81-0.97) was, however,&nbsp;significantly greater than that of NSE (0.77, 95% confidence interval: 0.64-0.90) (P=0.044). It was estimated that&nbsp;determination of protein S100B in all patients presenting to the ED with mild head trauma could safely save up to 50%&nbsp;CT execution, reducing the overall healthcare expenditure by ~1/3.</p>
Biochimica Clinica ; 38(3) 227-233
Opinioni - Opinions
Documento di consenso di “Academy of Emergency Medicine and Care”, Comitato Italiano per la Standardizzazione dei Metodi Ematologici e di Laboratorio, SIBioC - Medicina di Laboratorio e Società Italiana di Medicina di Laboratorio sull’utilizzo del dosaggi
Consensus document of Academy of Emergency Medicine and Care, Italian Committee for Standardization of Hematology and Laboratory Methods, SIBioC-Laboratory Medicine and Italian Society of Laboratory Medicine on D-dimer testing for suspected venous thrombo
G. Lippi  |  I. Casagranda  |  B. Morelli  |  S. Testa  |  A. Tripodi  | 
<p>The&nbsp;assessment of D-dimer represents the biochemical standard for diagnosing venous thromboembolism (VTE) and it&nbsp;is hence included in all diagnostic algorithms. Despite the unquestionable diagnostic value, there is broad evidence&nbsp;that the clinical usefulness of D-dimer may be biased by preanalytical, analytical and post-analytical issues. This is&nbsp;particularly true in emergency departments, where a large number of patients with suspected VTE is admitted, triaged&nbsp;and managed. Therefore, representatives of societies listed in the title have drafted this consensus document aimed&nbsp;to cover the most important critical areas in D-dimer testing, providing tentative recommendations to improve its&nbsp;clinical effectiveness for diagnosing VTE in the emergency department.</p>
Biochimica Clinica ; 38(2) 136-138
Documenti SIBioC - SIBioC Documents
Documento di consenso di Federazione dei Centri per la Diagnosi della Trombosi e la Sorveglianza delle Terapie Antitrombotiche (FCSA), Società Italiana di Medicina di Laboratorio (SIMeL), SIBioC e Comitato Italiano per la Standardizzazione dei Metodi Emat
Consensus document of Italian Federation of Thrombosis Services (FCSA), Italian Society of Laboratory Medicine (SIMeL), SIBioC e Italian Committee for Standardization of Laboratory Tests (CISMEL) on laboratory monitoring of the therapy with novel oral ant
G. Lippi  |  G. Di Iorio  |  S. Testa  |  C. Manotti  |  A. Tripodi  | 
<p>Oral anticoagulant therapy is used to prevent and&nbsp;treat thromboembolic disease. The new oral anticoagulants (NOAs) can be prescribed at fixed dosage without&nbsp;adjustment by laboratory testing. However, this does not necessarily mean that the laboratory does not play a role&nbsp;for their management. This position paper reports the consensus of Italian scientific societies dealing with laboratory&nbsp;issues in thrombosis and hemostasis. It is aimed at reviewing: a) which test(s) should be used to evaluate the&nbsp;anticoagulant effect of each of the NOAs presently available (i.e., dabigatran, rivaroxaban and apixaban), b) the&nbsp;patients to be investigated and c) the timing of investigation.</p>
Biochimica Clinica ; 37(4) 301-302
Documenti SIBioC - SIBioC Documents
Evaluation of Sysmex XE-2100 for enumeration and differentiation of cellular elements in peritoneal and pleural fluids
<p>The aim of this study was to evaluate the performance of Sysmex XE-2100 for automated flow cytometric analysis of<br />biological fluids. The results of 106 consecutive peritoneal samples and 20 pleural samples were compared with&#160;optical microscopy. A good agreement was found in total nucleated cells (TNC) count between Sysmex XE-2100 and&#160;manual microscopy (y=0.98x+3.2, r=0.99; mean bias, -9.5 TNC/&#956;L). The percentage of cells with high fluorescence&#160;in XE-2100 correlated with that of macrophages and mesothelial cells at microscopy (r=0.67; P &lt;0.001). The CV of&#160;TNC determination on XE-2100 ranged between 1.6% and 11.7%. At the 20% CV, the analytical sensitivity of XE-2100 was 29/&#956;L for TNC, 50/&#956;L for polymorphonuclear leukocytes (PMN) and 66/&#956;L for mononuclear elements. The&#160;linearity between 30 and 944 TNC/&#956;L was excellent (r=0.998, P &lt;0.001), whereas the carry-over was &lt;1%. At&#160;thresholds of &#8805;250 PMN/&#956;L in peritoneal fluid and &#8805;50% PMN or &#8805;50% lymphocytes in pleural fluid, the diagnostic&#160;accuracy of XE-2100 was 96.8%, with Cohen's kappa of 0.90 (P &lt;0.001). We conclude that automated flow&#160;cytometric analysis on Sysmex XE-2100 may be a viable options for screening of peritoneal and pleural fluids.</p>
Biochimica Clinica ; 37(4) 275-278
Contributi Scientifici - Scientific Papers
Il passaporto biologico dell’atleta: certezze e limiti
The athlete biological passport: facts and drawbacks
G. Lippi  | 
Biochimica Clinica ; 37(4) 265-267
Editoriale - Editorial
Note metodologiche sull’acquisizione e sull’uso dei sistemi chiusi sottovuoto per il prelievo, il trattamento e la conservazione dei campioni ematici venosi destinati alla diagnostica di laboratorio
Methodological notes on acquisition and use of close evacuated systems for collection, handling and storage of venous blood samples for laboratory diagnostics
M. Plebani  |  M. Caputo  |  D. Giavarina  |  G. Lippi  | 
<p>Evacuated systems for collection of venous blood&nbsp;are integrated systems of medical and in vitro diagnostic medical devices regulated under European Directives and&nbsp;Italian Legislative Decrees. Both Directives and Decrees endorse the requirement that the whole combination of&nbsp;devices, representing an integrated apparatus, must be safe and not impair the specific performance of each single&nbsp;device. According to mandatory requirements, manufacturers must ensure full compatibility between each component&nbsp;of the system, while the users are responsible for verifying the compatibility of different devices in order to avoid&nbsp;potential quality and safety problems. The acquisition of various devices from different manufacturers may lead to&nbsp;combinations that are not validated by manufacturers themselves and are thus expected to be validated and verified&nbsp;by the users to demonstrate that the system remains safe and will not impair the performance of the individual&nbsp;elements. Therefore, the possibility of purchasing different devices separately should be carefully weighted in terms&nbsp;of risk-benefit, taking into consideration the additional costs of the validation/verification process that should be&nbsp;carried out by the potential user. Since preanalytical problems are the major source of errors in the total testing&nbsp;process, the selection and acquisition of close evacuated systems for blood collection should be considered a critical&nbsp;issue for assuring quality, safety and efficiency of the preanalytical phase of laboratory diagnostics and, therefore, of&nbsp;the total testing process.</p>
Biochimica Clinica ; 37(4) 303-311
Documenti SIBioC - SIBioC Documents
Proposta di una “checklist” per il prelievo di sangue venoso
Proposal of a checklist for venous blood collection
<p>The collection of venous blood is central in clinical laboratory&nbsp;activity. Although there is widespread perception that this practice is simple and free of complications and side effects,&nbsp;it is undeniable that the vast majority of laboratory errors arises from ignorance, incompetence or negligence during&nbsp;venipuncture. It has hence become advisable to prepare a document in simplified form of checklist, consisting of a&nbsp;concise but comprehensive list of activities to be completed or verified in order to prevent errors during venous blood&nbsp;collection. In the intention of authors, this synthetic checklist is a modular tool, adaptable to different local contexts,&nbsp;it can be easily and gradually implemented, it is supported by scientific evidence and consensus of experts and&nbsp;created with the support of different healthcare professionals and it is adherent to the best practices and requires&nbsp;minimal resources for implementation. It is reasonable to assume that this checklist may be able to withstand system&nbsp;and individual changes, strengthening the standards for safety of both operators and patients, limiting potential failure&nbsp;patterns. We hope that the checklist may be implemented in all healthcare facilities where routine venous blood&nbsp;collection is performed, after adaptation to suit characteristics of local organization.</p>
Biochimica Clinica ; 37(4) 312-317
Documenti SIBioC - SIBioC Documents
Troponin elevation reflects myocardial injury in carbon monoxide poisoning
<p>We describe the case of a 48-year-old white man, who was admitted to the emergency department with neurologic&nbsp;deficits and high suspicion of carbon monoxide (CO) poisoning. Blood carboxyhemoglobin (COHb) level was found&nbsp;substantially increased (i.e., 18%). Clinical symptoms of myocardial infarction were lacking and the medical history&nbsp;was negative for major risk factors of coronary heart disease. However, electrocardiogram and troponin value were&nbsp;both suggestive for an acute coronary syndrome (i.e., a highly-sensitive troponin T value of 0.12 &mu;g/L), while the&nbsp;echocardiogram showed hypokinesia of left ventricular apical lateral wall. The coronary angiogram performed one&nbsp;week after admission did not reveal the presence of coronary obstructions. It is hence assumed that high levels of&nbsp;COHb in blood, such as after CO exposure, may trigger myocardial injury by severe generalized tissue hypoxia (i.e.,&nbsp;impaired oxygen delivery) and a direct toxic effect on myocardium. Contributing factors that also decrease myocardial&nbsp;oxygenation include inadequate myocardial perfusion and prothrombotic state. This case report suggests that&nbsp;increased troponin values, especially when measured with highly-sensitive immunoassays, may be observed in&nbsp;patients with CO poisoning, and mirror the presence of myocardial injury. Therefore, although the measurement of&nbsp;cardiac biomarkers may be advisable in the presence of CO toxicity to identify cardiac involvement, caution should&nbsp;be used when troubleshooting the underlying source of troponin elevations in order to preven t overdiagnosis or&nbsp;misdiagnosis of acute coronary syndrome.</p>
Biochimica Clinica ; 37(3) 246-249
Casi Clinici - Case Report
A case of acquired hemophilia A
G. Lippi  |  L. Ippolito  | 
<p>We describe the case of a 82 years old female, who has been referred to the emergency department for a gross trauma of the right knee after an accidental fall. Physical examination revealed a palpable mass in the right pelvis, which was then identified as a large intramuscular hematoma of the right iliacus muscle by computerized tomography scan. The most suggestive laboratory findings were anemia and a prolonged activated partial thromboplastin time (APTT) (ratio 1.33), with physiological platelet count and prothrombin time. After ten days of hospitalization, when a spontaneous hematoma developed in the right arm, APTT had steadily increased, up to a value of 3.33. A mixing study and assessment of coagulation factors were rapidly performed. The former test was not effective to normalized the APTT, whereas concentrations of all factors were within the reference interval, except for factor VIII (0.6%). Factor VIII inhibitor titration using Bethesda assay confirmed the diagnosis of acquired hemophilia A, yielding a value of 77 Bethesda units. Acquired hemophilia A, which is caused by autoantibodies against coagulation factor VIII, is a rare condition that can be frequently overlooked or misdiagnosed. The role of laboratory diagnostics is thereby as important as the clinics, wherein serious hemorrhages accompanied by variable APTT prolongations onset in a previously asymptomatic patient. Along with discussion about laboratory and clinical aspects of acquired hemophilia A, we present a diagnostic algorithm for efficiently troubleshooting prolonged APTT values in clinical laboratories.</p>
Biochimica Clinica ; 37(2) 128-130
Casi clinici - Case Report
Raccomandazioni di consenso SIBioC-SIMeL per la rilevazione e gestione dei campioni emolisati e utilizzo dell'indice di emolisi
SIBioC-SIMeL consensus recommendations for the identification and management of hemolysed specimens and the implementation of hemolysis index
<p><strong>SIBioC-SIMeL consensus recommendations for the identification and management of hemolysed specimens</strong><br /><strong>and the implementation of hemolysis index.</strong> The presence of hemolysis in a biological blood sample is mainly<br />caused by hemolytic anemia or hemolysis in vitro. The latter is caused by inappropriate collection and processing of biological samples, which may affect the reliability of test results. Hemolysis is assessed by free hemoglobin quantification, whose limit is 0.02 g/L in plasma and 0.05 g/L in serum, and visually observed when the concentration of free hemoglobin exceeds 0.30 g/L. Since hemolysis is the most frequent cause of unsuitable biological samples in clinical laboratories, with a prevalence approaching 3% of all received samples, these recommendations have been drafted specifically to assist laboratory professionals in detection and management of hemolysed specimens. In summary, the recommended approach is based on: (i) systematic detection and quantification of hemolysis, by visual inspection and subsequent quantification of the hemolysis index on all samples with visually detectable hemolysis; (ii) immediate notification to the referring department of the presence of hemolysis in the sample, as locally determined; (iii) suppression of all results affected by the presence and/or degree of hemolysis; and (iv) timely request of a second sample, on which the previously deleted tests can be performed.</p>
Biochimica Clinica ; 35(6) 481-490
Valutazione del "risk of ovarian malignancy algorithm" (ROMA) nella stima del rischio di tumore epiteliale maligno dell'ovaio in donne con massa pelvica
The "risk of ovarian malignancy algorithm" for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass.
Biochimica Clinica ; 35(1) 30
Guida sintetica alla diagnostica della malattia da coronavirus 2019 (COVID-19)
Concise guide to coronavirus disease 2019 (COVID-19) diagnostics
<p>Several months after its emergence, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still prepotently disrupting health, societies and economies worldwide. The current approach for diagnosing SARS-CoV-2 remains based on identification of viral RNA by means of molecular biology techniques in upper or lower respiratory tracts specimens. Nevertheless, the development of immune response against the virus may also provide valuable diagnostic information. The paradigmatic kinetics of anti-SARS-CoV-2 antibodies in patients with COVID-19 would allow to conclude that serological testing shall not replace viral RNA detection in diagnosing acute SARS-CoV-2 infection, but may instead remain an essential tool for identifying patients who have been infected and have developed an immune response, as well as for monitoring the progress of herd immunity. For this purpose, the choice of the antigens used for constructing the immunoassays appears critical, as these shall use epitopes towards which neutralizing antibodies could be generated. Other important aspects in serological testing encompass the absence of cross-reactivity with other coronaviruses, the ability to distinguish the antibody class (i.e. IgG, IgA and/or IgM), quantitative assessment, wide range of linearity and low imprecision at diagnostic thresholds. A finalaspect, almost essential for both clinical and public health purposes, is the evidence of analytical and clinical validation before each method enters clinical practice.</p>
Biochimica Clinica ; 17(1) 003-004
Iper-infiammazione e squilibrio del sistema renina-angiotensina-aldosterone in corso di COVID-19: una nuova ipotesi per il sospetto clinico di ipercoagulabilità e immuno-trombosi microvascolare
Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis.
BM. Henry  |  J. Vikse  |  S. Benoit  |  EJ. Favaloro  |  G. Lippi  | 
<p>Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to&nbsp;reverse the otherwise unfavorable clinical outcome of many of these patients.</p>
Biochimica Clinica ; 17(1) 007-008
Prevalenza di anticorpi anti-SARS-CoV-2 in una popolazione di operatori sanitari e amministrativi di un ospedale toscano
Serum prevalence of anti-SARS-CoV-2 antibody in a population of health care and administrative workers in a hospital in Tuscany (Italy).
F. Balboni  |  A. Baldini  |  G. Forgeschi  |  F. Sequi  |  S. Burbui  |  G. Lippi  | 
<p>Introduction: the challenges due to COVID-19 pandemic forced scientific community to focus their efforts to improve diagnosis and management of patients. The recognized gold standard for the diagnosis is the reverse transcription polymerase chain reaction (RT-PCR) on orofaringeal and nasal swabs. Recently, the antibody detection surge to attention with the aim of estimating the epidemiological impact of the pandemic.<br />Methods: the Screen Test COVID-19 2019-nCov IgG/IgM (Screen Italia, Perugia, Italy) an immunochromatographic lateral flow test has been used to assess the immunological status of 356 asymptomatic healthcare and administrative workers of our hospital.<br />Results: only 26 (7.3%) of the screened subjects was positive for IgM and/or IgG anti SARS-CoV-2 virus although the beginning of the epidemic in Tuscany can be dated two months before. The RT-PCR performed on these samples revealed that only 5 (19%) of them were positive for viral RNA on orofaringeal swab.<br />Conclusions: antibody detection will be of great value in the near future to assess global pandemic impact on population and to drive health policy for the lock down release.</p>
Biochimica Clinica ; 17(1) 023-024