Maria Stella Graziani

Deputy Director
Martina Zaninotto

Associate Editors
Ferruccio Ceriotti
Davide Giavarina
Bruna Lo Sasso
Giampaolo Merlini
Martina Montagnana
Andrea Mosca
Paola Pezzati
Rossella Tomaiuolo
Matteo Vidali

International Advisory Board Khosrow Adeli Canada
Sergio Bernardini Italy
Marcello Ciaccio Italy
Eleftherios Diamandis Canada
Philippe Gillery France
Kjell Grankvist Sweden
Hans Jacobs The Netherlands
Eric Kilpatrick UK
Magdalena Krintus Poland
Giuseppe Lippi Italy
☩Howard Morris Australia
Mario Plebani Italy
Sverre Sandberg Norway
Ana-Maria Simundic Croatia
☩Jill Tate Australia
Tommaso Trenti Italy
Cas Weykamp The Netherlands
Maria Willrich USA
Paul Yip Canada

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Giuseppe Agosta

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Arianna Lucini Paioni
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Biochimica Clinica: VOL.37 N.2

Epcidina: un nuovo marcatore biologico?
Hepcidin: a new biomarker?
Biochimica Clinica 2013; 37(2) 084-085
Editoriale - Editorial
Adrenomedullina e peptidi correlati: dalla fisiologia alla diagnostica
Adrenomedullin and related peptides: from physiology to diagnostics

Adrenomedullin (ADM) and related peptides have important physiologic effects on cardiovascular system, including a potent and powerful hypotensive activity caused by dilatation of resistance vessels. Other roles are played in endocrine and nervous systems. The plasma concentrations of ADM are increased in several cardiac diseases, raising the possibility of a role as a biomarker of heart failure. The actions of ADM are generally protective and beneficial to organs and tissues (e.g., vasodilation, natriuresis and anti-inflammation) and suggest that increased ADM expression or activity could act as a compensatory response to end-organ injury. The investigations on the possible applications of ADM in clinical studies have increased since the introduction of an assay measuring mid-regional proadrenomedullin (MR-proADM), a peptide derived from proadrenomedullin characterized by a high stability in plasma. Recent studies suggest that MRproADM could be a marker of adverse prognostic effects after myocardial infarction or during acute cardiac dyspnea. Recently, our group showed that MR-proADM is a powerful prognostic marker in AL (light-chain) amyloidosis, which may not only reflect cardiac dysfunction, but also widespread systemic disease, and can be combined with cardiac troponin for detecting patients at risk of early death. However, further studies are required in order to recommend the assay of MR-proADM in the clinical laboratory; in particular, there is a lack of information about: 1) kinetics of MRproADM release after acute events and 2) the specific contribution given by MR-proADM assay in addition to the wellestablished determination of natriuretic peptides.

Biochimica Clinica 2013; 37(2) 086-090
Rassegne - Reviews
Il laboratorio nella diagnosi differenziale fra artrite reumatoide precoce e poliartropatia correlata a infezione cronica da virus dell’epatite C
The laboratory in the differential diagnosis between early rheumatoid arthritis and polyarthropathy related to chronic infection with hepatitis C virus

Articular involvement is a frequent extrahepatic manifestation of hepatitis C virus (HCV) infection. The distinction between HCV-related polyarthropathy and true rheumatoid arthritis (RA) may be very difficult, especially in patients with recent onset RA before articular damage and erosions develop. The aim of this study was to assess the diagnostic utility of anti-cyclic citrullinated peptide (CCP) antibodies, in comparison with isotype rheumatoid factor (RF), in distinguishing between RA (early and long-standing) and HCV-related polyarthropathy. Anti-CCP and RF IgM and IgA were evaluated in sera of 185 patients with long-standing RA, 100 patients with early RA and 126 patients with HCV infection, 20 of which with related arthropathy. Anti-CCP antibodies were positive in 66.5% and 9.0 % of patients with long-standing AR and early AR, respectively, whereas they were positive in 3.9% of patients with HCV infection. RF IgM were positive in 77.3%, 35.0% and 53.2% of patients with long-standing AR, early AR and HCV infection, respectively. Finally, RF IgA were positive in 62.1%, 25.0% and 7.2% of patients with long-standing AR, early AR and HCV infection, respectively. In the HCV positive population under study, all patients without articular involvement did not show positivity for IgA isotype of RF, while it was positive in 45% of those with arthropathy. In particular, all patients characterized by poliarthropathy showed positivity for IgA isotype of RF. Therefore, the determination of IgA isotype RF can improve the detection of HCV chronic infection patients with associated polyarthropathy.

Biochimica Clinica 2013; 37(2) 091-094
Contributi scientifici - Scientific Papers
Rilevazione, monitoraggio e trattamento di non conformità nella fase preanalitica: l’esperienza di un ospedale universitario metropolitano
Recording, monitoring, and managing pre-analytical issues in a metropolitan university hospital

Errors in laboratory testing process may have an adverse impact on patient care. The pre-analytical phase is responsible for ~70% of these errors. In this study we present our experience in assessing the frequency of pre-analytical errors in our university hospital, by monitoring their trend over time and comparing data with goals suggested in literature. The impact of corrective actions, if any, was also checked. A comprehensive retrospective analysis of pre-analytical nonconformities (NC) recorded through laboratory information system over a 5-year (2007-2011) time span was undertaken. Retrieved data were evaluated on a yearly basis, first for NC type and then for type of sample, laboratory section and hospital department involved. The relatively most frequent NC was the test request without the corresponding sample, accounting on average for 2.3% of all requested tests. Hemolysis occurred for in average 1.15% of all requested tests, affecting ~20,000 determinations per year, mostly interesting clinical wards taking care of critical patients, i.e. neonatology, oncology, and emergency department. Clotted and not sufficient samples showed a significant reduction over time after changing the analytical system measuring erythrocyte sedimentation rate and adopting more reliable tubes, easier to fill in and mix up. NC related to samples conveyed at wrong temperature were also relatively frequent. Our results show that recording, monitoring, and critically evaluating pre-analytical issues in laboratory testing process is mandatory for providing a good laboratory service, permitting to identify causes of NC and to apply corrective interventions that may help to reduce their incidence.

Biochimica Clinica 2013; 37(2) 095-099
Contributi scientifici - Scientific Papers
Standardizzazione della misura e traguardi analitici per l’emoglobina glicata
Measurement standardization and analytical goals for glycated hemoglobin

Glycated hemoglobin (HbA1c) plays a key role in diagnosing diabetes and monitoring the glycemic state. To guarantee the reliability of its measurement at global level, IFCC has defined a reference measurement system, based on the definition of the measurand as hemoglobin molecules having a special hexapeptide in common, which is the stable adduct of glucose to the N-terminal valine of the hemoglobin b-thechain. In addition to the traceability of HbA1c results to the reference system, the establishment of analytical goals to make HbA1c measurements clinically reliable becomes crucial. However, allowable goals will depend on the assay specificity (i.e., selectivity) and, consequently, on units in which HbA1c results are expressed [mmol/mol for IFCC-aligned systems or % for National Glycohemoglobin Standardization Program (NGSP) converted numbers]. In this regard, analytical goals derived from biologic variability studies in which the determination of HbA1c has been carried out by an assay providing the same selectivity for the measurand as defined by the IFCC are recommended. Only these targets should be used for evaluating the performance of commercial assays traceable to the IFCC system and of clinical laboratories using them through appropriately structured quality controls. Analytical systems following different calibration hierarchies (e.g., the NGSP-aligned assays) will require different analytical goals.

Biochimica Clinica 2013; 37(2) 100-107
Opinioni - Opinions
Implicazioni diagnostiche dell’epcidina nelle patologie interessanti il metabolismo del ferro
Hepcidin in human iron disorders: diagnostic implications

The peptide hormone hepcidin plays a central role in regulating dietary iron absorption and body iron distribution. Many human diseases are associated with alterations in hepcidin concentrations. The measurement of hepcidin in biological fluids is therefore a promising tool in the diagnosis and management of medical conditions in which iron metabolism is affected. We describe hepcidin structure, kinetics, function, and regulation. We moreover explore the therapeutic potential for modulating hepcidin expression and the diagnostic potential for hepcidin measurements in clinical practice. Cell-culture, animal, and human studies have shown that hepcidin is predominantly synthesized by hepatocytes, where its expression is regulated by body iron status, erythropoietic activity, oxygen tension, and inflammatory cytokines. Hepcidin lowers serum iron concentrations by counteracting the function of ferroportin, a major cellular iron exporter present in the membrane of macrophages, hepatocytes, and the basolateral site of enterocytes. Hepcidin is detected in biologic fluids as a 25 amino acid isoform, hepcidin-25, and two smaller forms, i.e., hepcidin-22 and -20; however, only hepcidin-25 has been shown to participate in the regulation of iron metabolism. Reliable assays to measure hepcidin in blood and urine by use of immunochemical and mass spectrometry methods have been developed. Results of proof-of-principle studies have highlighted hepcidin as a promising diagnostic tool and therapeutic target for iron disorders. However, before hepcidin measurements can be used in routine clinical practice, efforts will be required to assess the relevance of hepcidin isoform measurements, to harmonize the different assays, to define clinical decision limits, and to increase assay availability for clinical laboratories.

Biochimica Clinica 2013; 37(2) 108-127
Il meglio di Clinical Chemistry - Clinical Chemistry highlights
A case of acquired hemophilia A
G. Lippi  |  L. Ippolito  | 

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.

Biochimica Clinica 2013; 37(2) 128-130
Casi clinici - Case Report
Inaccurate HbA1c determination caused by Hb Aix-les-Bains, a rare hemoglobin variant
Biochimica Clinica 2013; 37(2) 131-132
Lettere all'Editore - Letters to the Editor
Un ulteriore passo verso una migliore efficienza ed efficacia della determinazione della calprotectina fecale
A further step to improve the cost-effectiveness of calprotectin determination
Biochimica Clinica 2013; 37(2) 133-134
Lettere all'Editore - Letters to the Editor
Determinazione dell’epcidina: ma cosa stiamo “misurando”?
Quantification of hepcidin: what are we measuring?
Biochimica Clinica 2013; 37(2) 135-137
Lettere all'Editore - Letters to the Editor
EuroMedLab 2013 Scientific Programme
Biochimica Clinica 2013; 37(2) 138-155
Convegni e congressi - Scientific Meetings
EuroMedLab 2013 Satellite Meetings Programmes
Biochimica Clinica 2013; 37(2) 156-161
Convegni e congressi - Scientific Meetings