Browsing by Author "Noris, Patrizia"

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    A review of platelet secretion assays for the diagnosis of inherited platelet secretion disorders
    (2015) Mumford, Andrew D.; Frelingerm III, Andrew L.; Gachet, Christian; Gresele, Paolo; Noris, Patrizia; Harrison, Paul; Mezzano, Diego
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    Expert opinion on the use of platelet secretion assay for the diagnosis of inherited platelet function disorders: Communication from the ISTH SSC Subcommittee on Platelet Physiology
    (2022) Mezzano, Diego; Harrison, Paul; Frelinger, Andrew L., III; Mumford, Andrew D.; Noris, Patrizia; Lordkipanidze, Marie; Gresele, Paolo
    Assessment of platelet secretion is crucial for diagnosing suspected inherited platelet function disorders (IPFD). A previous survey of the SSC on Platelet Physiology of the ISTH and a comprehensive review highlighted that most of the platelet secretion assays (PSAs) lack standardization and validation. The aim of this study was to provide expert consensus guidance on the use of PSAs for IPFD diagnosis. We surveyed 26 experts from 10 different countries using the RAND/UCLA methodology, to attain a consensus on sensitivity, specificity, feasibility, time to readout, and cost of most PSAs. Answers were then graded in three categories: appropriate, uncertain, and inappropriate. Equivocal or misinterpretable statements required a second and third round survey involving 14 of the original 26 experts. We report here the consolidated results of the entire procedure. There was uniform agreement on several general statements, including that PSAs should be performed in hemostasis laboratories as first line diagnostic tests even in patients with normal platelet aggregation, and should include a delta-granule secretion marker. Among the specific assays examined, lumiaggregometry, other luciferin/luciferase-based assays, high-performance liquid chromatography methods, radiolabeled-serotonin based assays, and whole-mount transmission electron microscopy were rated as appropriate for the measurement of delta-granule release, and platelet P-selectin expression by flow cytometry and released proteins by ELISA for alpha-granule release. For most of the other PSAs, the expert opinions were widely dispersed. Lack of expert consensus on many PSAs clearly indicates an unmet need for rigorous standardization, multicenter comparison of results, and validation of PSAs for clinical laboratory practice.
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    Fundamentals for a Systematic Approach to Mild and Moderate Inherited Bleeding Disorders: An EHA Consensus Report
    (2019) Rodeghiero, Francesco; Pabinger, Ingrid; Ragni, Margaret; Abdul-Kadir, Rezan; Berntorp, Erik; Blanchette, Victor; Bodo, Imre; Casini, Alessandro; Gresele, Paolo; Lassila, Riitta; Leebeek, Frank; Lillicrap, David; Mezzano, Diego; Noris, Patrizia; Srivastava, Alok; Tosetto, Alberto; Windyga, Jerzy; Zieger, Barbara; Makris, Mike; Key, Nigel
    Healthy subjects frequently report minor bleedings that are frequently 'background noise' of normality rather than a true disorder. Nevertheless, unexpected or unusual bleeding may be alarming. Thus, the distinction between normal and pathologic bleeding is critical. Understanding the underlying pathologic mechanism in patients with an excessive bleeding is essential for their counseling and treatment. Most of these patients with significant bleeding will result affected by non-severe inherited bleeding disorders (BD), collectively denominated mild or moderate BD for their relatively benign course. Unfortunately, practical recommendations for the management of these disorders are still lacking due to the current state of fragmented knowledge of pathophysiology and lack of a systematic diagnostic approach. To address this gap, an International Working Group (IWG) was established by the European Hematology Association (EHA) to develop consensus-based guidelines on these disorders. The IWG agreed that grouping these disorders by their clinical phenotype under the single category of mild-to-moderate bleeding disorders (MBD) reflects current clinical practice and will facilitate a systematic diagnostic approach. Based on standardized and harmonized definitions a conceptual unified framework is proposed to distinguish normal subjects from affected patients. The IWG proposes a provisional comprehensive patient-centered initial diagnostic approach that will result in classification of MBD into distinct clinical-pathological entities under the overarching principle of clinical utility for the individual patient. While we will present here a general overview of the global management of patients with MBD, this conceptual framework will be adopted and validated in the evidence-based, disease-specific guidelines under development by the IWG.
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    Validation of the ISTH/SSC bleeding assessment tool for inherited platelet disorders: A communication from the Platelet Physiology SSC
    (2020) Gresele, Paolo; Orsini, Sara; Noris, Patrizia; Falcinelli, Emanuela; Alessi, Marie Christine; Bury, Loredana; Borhany, Munira; Santoro, Cristina; Glembotsky, Ana C.; Rosa Cid, Ana; Tosetto, Alberto; De Candia, Erica; Fontana, Pierre; Guglielmini, Giuseppe; Pecci, Alessandro; Melazzini, Federica; Falaise, Celine; Casonato, Alessandra; Podda, Gianmarco; Kannan, Meganathan; Jurk, Kerstin; Sevivas, Teresa; Castaman, Giancarlo; Grandone, Elvira; Fiore, Mathieu; Zuniga, Pamela; Henskens, Yvonne; Miyazaki, Koji; Dupuis, Arnaud; Hayward, Catherine; Zaninetti, Carlo; Abid, Madiha; Ferrara, Grazia; Mazzucconi, Maria Gabriella; Tagariello, Giuseppe; James, Paula; Fabris, Fabrizio; Russo, Alexandra; Bermejo, Nuria; Napolitano, Mariasanta; Curnow, Jennifer; Vasiliki, Gkalea; Zieger, Barbara; Fedor, Marian; Chitlur, Meera; Lambert, Michele; Barcella, Luca; Cosmi, Benilde; Giordano, Paola; Porri, Claudia; Eker, Ibrahim; Morel-Kopp, Marie-Christine; Deckmyn, Hans; Frelinger, Andrew L., III; Harrison, Paul; Mezzano, Diego; Mumford, Andrew D.
    Background Careful assessment of bleeding history is the first step in the evaluation of patients with mild/moderate bleeding disorders, and the use of a bleeding assessment tool (BAT) is strongly encouraged. Although a few studies have assessed the utility of the ISTH-BAT in patients with inherited platelet function disorders (IPFD) none of them was sufficiently large to draw conclusions and/or included appropriate control groups. Objectives The aim of the present study was to test the utility of the ISTH-BAT in a large cohort of patients with a well-defined diagnosis of inherited platelets disorder in comparison with two parallel cohorts, one of patients with type-1 von Willebrand disease (VWD-1) and one of healthy controls (HC). Patients/Methods We enrolled 1098 subjects, 482 of whom had inherited platelet disorders (196 IPFD and 286 inherited platelet number disorders [IT]) from 17 countries. Results IPFD patients had significantly higher bleeding score (BS; median 9) than VWD-1 patients (median 5), a higher number of hemorrhagic symptoms (4 versus 3), and higher percentage of patients with clinically relevant symptoms (score > 2). The ISTH-BAT showed excellent discrimination power between IPFD and HC (0.9 < area under the curve [AUC] < 1), moderate (0.7 < AUC < 0.9) between IPFD and VWD-1 and between IPFD and inherited thrombocytopenia (IT), while it was inaccurate (AUC <= 0.7) in discriminating IT from HC. Conclusions The ISTH-BAT allows to efficiently discriminate IPFD from HC, while it has lower accuracy in distinguishing IPFD from VWD-1. Therefore, the ISTH-BAT appears useful for identifying subjects requiring laboratory evaluation for a suspected IPFD once VWD is preliminarily excluded.