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1. Short versus long-term anticoagulation for left ventricular thrombosis resolution during vitamin k antagonist therapy

Author

Valeriani, E, primary, Pastori, D, additional, Astorri, G, additional, Ageno, W, additional, Donadini, M P, additional, Santagata, D P, additional, Becattini, C, additional, Satula, K, additional, De Candia, E, additional, D'innocenzo, L, additional, Tufano, A, additional, Marcucci, R, additional, Berteotti, M, additional, Bucci, T, additional, and Pignatelli, P, additional

Published
2023
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2. D-dimer and reduced dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study

Author

Palareti, G., Poli, D., Pesavento, R., Legnani, C., Antonucci, E., Bucherini, E., Testa, S., Paoletti, O., Chistolini, A., Ceccato, D., Martinelli, I., Bucciarelli, P., Falanga, A., Tosetto, A., Sarti, L., Mastroiacovo, D., Cosmi, B., Visona, A., Santoro, R. C., Zanatta, N., Grandone, E., Bertu, L., Pengo, V., Caiano, L., Prandoni, P., Lotti, E., Crudele, F., Ageno, W., Abenante, A., Colombo, G., Guarascio, M., Cancellieri, E., Morandini, R., Zambelli, S., Martini, S., Vastola, M., Serrao, A., Abbattista, M., Artoni, A., Capecchi, M., Gianniello, F., Scimeca, B., Barcella, L., Gamba, S., Lerede, T., Maggioni, A., Schieppati, F., Russo, L., Zunino, F., Artuso, A., Bellesso, S., Cadau, J., Carli, G., Nichele, I., Perbellini, O., Caronna, A., Gabrielli, F., Lami, F., Nicolini, A., Scaglioni, F., Pinelli, M., Desideri, G., Borgese, L., Favaretto, E., Libra, A., Migliaccio, L., Sartori, M., Panzavolta, C., Scandiuzzi, T., Zalunardo, B. -M., Ierardi, A., Leotta, M., Strangio, A., Guzzon, S., Colaizzo, D., Favuzzi, G., Lombardi, M. R., Ferrini, P. M., Tassoni, M. I., Corradini, S., Iotti, M., Lambertini, I., Veropalumbo, M. R., Lessiani, G., Parisi, R., Bortoluzzi, C., H. N., Vo, Chiarugi, P., Casini, M., Violo, C., Nuti, M., Angeloni, L., Carrozzi, L., Pancani, R., Chimera, D., Conti, V., Meschi, C., Cattaneo, M., Podda, G., Birocchi, S., Cuppini, S., Marzolo, M., Milan, M., Martini, G., Merelli, S., Pontoglio, S., Portesi, N., Villalta, S., De Lucchi, L., Sponghiado, A., Becattini, C., Giustozzi, M., Vinci, A., Pignatelli, P., Bucci, T., Menichelli, D., Pastori, D., Pomero, F., Casalis, S., Galli, E., Ciammaichella, M., Maida, R., De Cristofaro, R., Alberelli, M. A., Basso, M. R., De Candia, E., Di Gennaro, L., Mumoli, N., Capra, R., Orlando, M., Porta, C., Rotiroti, G., Demarco, M., Petrillo, P., Rossi, E., Bartolomei, F., Soldati, D., Russo, U., Burgo, I., Ziliotti, M., Pataccini, C., Terroni, L., Ugolotti, M. C., Di Giorgio, A., Cavagna, L., Mete, F., Gino, M., Santoro, A., De Carlo, A., Cappelli, R., Bicchi, M., Dyrmo, L., Grifoni, E., Masotti, L., Ria, L., Spagnolo, M., Rupoli, S., Federici, I., Morsia, E., Scortechini, A. R., Torre, E., Franchini, M., Montorsi, P., Galgano, G., De Luca, A., Muiesan, M. L., Paini, A., Stassaldi, D., Denas, G., and Palareti G, Poli D, Ageno W, Legnani C, Antonucci E, Bucherini E, Testa S, Paoletti O, Chistolini A, Serrao A, Martinelli I, Bucciarelli P, Falanga A, Tosetto A, Sarti L, Mastroiacovo D, Cosmi B, Visonà A, Santoro RC, Zanatta N, Grandone E, Bertù L, Pengo V, Caiano LM, Prandoni P

Subjects
venous thromboembolism, d-dimer, anticoagulation therapy, apixaban, anticoagulation therapy, Recurrence, Settore MED/09 - MEDICINA INTERNA, D-dimer, venous thromboembolism, oral anticoagulants, apixaban, Humans, Anticoagulants, Hematology, Prospective Studies, Venous Thromboembolism, d-dimer
Abstract

D-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study, we aimed to assess the value of an algorithm incorporating serial D-dimer testing and administration of reduced-dose apixaban (2.5 mg twice daily) only to patients with a positive test. A total of 732 outpatients aged 18 to 74 years, anticoagulated for ≥12 months after a first unprovoked VTE, were included. Patients underwent D-dimer testing with commercial assays and preestablished cutoffs. If the baseline D-dimer during anticoagulation was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286 [39.1%]) were left without anticoagulation. At the first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% confidence interval [CI], 4.5-11.2), including symptomatic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) recurrence, death for VTE, and major bleeding occurring in patients off anticoagulation vs that in those receiving apixaban (1.1%; 95% CI, 0.4-2.6; adjusted hazard ratio [HR], 8.2; 95% CI, 3.2-25.3). In conclusion, in patients anticoagulated for ≥1 year after a first unprovoked VTE, the decision to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced-dose apixaban against recurrences. This trial was registered at www.clinicaltrials.gov as #NCT03678506.

Published
2022

3. The ISTH bleeding assessment tool as predictor of bleeding events in inherited platelet disorders: Communication from the ISTH SSC Subcommittee on Platelet Physiology

Author

Gresele, P., Falcinelli, E., Bury, L., Pecci, A., Alessi, M. -C., Borhany, M., Heller, P. G., Santoro, C., Cid, A. R., Orsini, S., Fontana, P., De Candia, E., Podda, G., Kannan, M., Jurk, K., Castaman, G., Falaise, C., Guglielmini, G., Noris, P., Zaninetti, C., Fiore, M., Tosetto, A., Zuniga, P., Miyazaki, K., Dupuis, A., Hayward, C., Casonato, A., Grandone, E., Mazzucconi, M. G., James, P., Fabris, F., Henskens, Y., Napolitano, M., Curnow, J., Gkalea, V., Fedor, M., Lambert, M. P., Zieger, B., Barcella, L., Cosmi, B., Giordano, P., Porri, C., Melazzini, F., Abid, M., Glembotsky, A. C., Ferrara, G., Russo, A., Deckmyn, H., Frelinger, A. L., Harrison, P., Mezzano, D., Mumford, A. D., Lordkipanidzé, M., BAT-VAL Study Investigators, Università degli Studi di Perugia = University of Perugia (UNIPG), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unidad de Coagulopatías Congénitas. Hospital Universitario La Fe., Gresele, Paolo, Falcinelli, Emanuela, Bury, Loredana, Pecci, Alessandro, Alessi, Marie-Christine, Borhany, Munira, Heller, Paula G, Santoro, Cristina, Cid, Ana Rosa, Orsini, Sara, Fontana, Pierre, De Candia, Erica, Podda, Gianmarco, Kannan, Meganathan, Jurk, Kerstin, Castaman, Giancarlo, Falaise, Céline, Guglielmini, Giuseppe, Noris, Patrizia, Mariasanta Napolitano, Università degli Studi di Perugia (UNIPG), University of Perugia, Gresele, P., Falcinelli, E., Bury, L., Pecci, A., Alessi, M.-C., Borhany, M., Heller, P.G., Santoro, C., Cid, A.R., Orsini, S., Fontana, P., De Candia, E., Podda, G., Kannan, M., Jurk, K., Castaman, G., Falaise, C., Guglielmini, G., Noris, P., Zaninetti, C., Fiore, M., Tosetto, A., Zuniga, P., Miyazaki, K., Dupuis, A., Hayward, C., Casonato, A., Grandone, E., Mazzucconi, M.G., James, P., Fabris, F., Henskens, Y., Napolitano, M., Curnow, J., Gkalea, V., Fedor, M., Lambert, M.P., Zieger, B., Barcella, L., Cosmi, B., Giordano, P., Porri, C., Melazzini, F., Abid, M., Glembotsky, A.C., Ferrara, G., Russo, A., Deckmyn, H., Frelinger, A.L., Harrison, P., Mezzano, D., Mumford, A.D., Lordkipanidzé, M., and BAT-VAL Study Investigators

Subjects
medicine.medical_specialty, animal structures, mild&#8208, Platelet Function Tests, Platelet disorder, inherited platelet disorder, Hemorrhage, 030204 cardiovascular system & hematology, Hemorrhage/diagnosis, 03 medical and health sciences, 0302 clinical medicine, Von Willebrand factor, hemic and lymphatic diseases, Internal medicine, von Willebrand Factor, Von Willebrand disease, Medicine, Humans, Platelet, Bleeding prediction, Bleeding score, Blood platelet disorders, Child, Communication, Hemorrhage, Humans, Inherited platelet disorders, Mild-moderate bleeding disorders, Platelet Function Tests, von Willebrand diseases, von Willebrand Factor, Child, Blood Platelet Disorders, ddc:616, mild-moderate bleeding disorders, biology, business.industry, mild-moderate bleeding disorder, Incidence (epidemiology), Communication, Settore MED/09 - MEDICINA INTERNA, bleeding prediction, von Willebrand Diseases/diagnosis/genetics, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Blood Platelet Disorders/diagnosis/genetics, 3. Good health, bleeding score, Institutional repository, von Willebrand Diseases, moderate bleeding disorders, inherited platelet disorders, Quartile, biology.protein, von Willebrand disease, business
Abstract

Background: The ISTH Bleeding Assessment Tool (ISTH-BAT) has been validated for clinical screening of suspected von Willebrand disease (VWD) and for bleeding prediction. Recently it has been validated for subjects with inherited platelet disorders (IPD) (BAT-VAL study). Objectives: To determine whether the ISTH-BAT bleeding score (BS) predicts subsequent bleeding events requiring treatment in IPD patients. Methods: Patients with IPD, type 1 VWD (VWD-1) and age- and sex-matched healthy controls enrolled in the BAT-VAL study were prospectively followed-up for 2years and bleeding episodes requiring treatment were recorded. Results: Of the 1098 subjects initially enrolled, 955 were followed-up and 124 suffered hemorrhages during follow-up, 60% of whom had inherited platelet function disorders (IPFD). Total number of events was significantly higher in IPFD (n=235) than VWD-1 (n=52) or inherited thrombocytopenia (IT; n=20). Events requiring transfusions were 66% in IPFD, 5.7% in VWD-1, and 3% in IT. Baseline BS was significantly higher in IPFD patients with a bleeding event at follow-up than in those without (p&nbsp

Published
2021

6. Outcomes of 339 pregnancies in 181 women suffering from 13 different forms of inherited thrombocytopenia enrolled in a retrospective and multicentric study (on behalf of EHA-SWG on thrombocytopenias and platelet function disorders): WH09

Author

Noris, P, Schlegel, N, Klersy, C, Heller, P G, Civaschi, E, Pujol-Moix, N, Fabris, F, Favier, R, Gresele, P, Latger-Cannard, V, Cuker, A, Nurden, P, Greinacher, A, Cattaneo, M, De Candia, E, Pecci, A, Hurtaud-Roux, M-F, Glembotsky, A C, Muñiz-Diaz, E, Randi, M L, Trillot, N, Bury, L, Lecompte, T, Marconi, C, Savoia, A, and Balduini, C L

Published
2014

7. Consensus statements on vaccination in patients with haemophilia—Results from the Italian haemophilia and vaccinations (HEVA) project

Author

Santagostino E., Riva A., Cesaro S., Esposito S., Matino D., Mazzucchelli R. I., Molinari, Angelo Claudio, Mura R., Notarangelo L. D., Tagliaferri A., Di Minno G., Clerici M., Ambaglio C., Brigida Aru A., Baldacci E., Barillari G., Basso M., Bernasconi S., Bertamino M., Bertoni E., Biasoli C., Federica Biguzzi E., Bonetti E., Borchiellini A., Bulgarelli S., Cabibbo S., Cantori I., Castaman G., Castiglia P., Coluccia A., Coppetelli U., Coppola A., Cultrera D., De Candia E., Delios G., Di Gennaro L., Di Gregorio P., Di Minno M., Dragani A., Pietro Ettorre C., Franchini M., Galli M., Gallo G., Giordano P., Giuffrida G., Iannaccaro P., Lassandro G., Lazzareschi I., Linari S., Luciani M., Macchi S., Malcangi G., Malizia R., Marietta M., Marino R., Massoud M., Gabriella Mazzucconi M., Milan M., Morfini M., Napolitano M., Pasca S., Pedrazzi P., Peyvandi F. A., Piscitelli L., Pollio B., Preti P., Quintavalle G., Radossi P., Raso S., Ricca I., Rocino A., Santoro C., Carlotta Santoro R., Sarolo L., Schiavoni M., Schiavulli M., Sciancalepore P., Luisa Serino M., Mario Siragusa S., Sottilotta G., Svahn J., Valdre L., Cristina Vedovati M., Zanon E., Santagostino, E., Riva, A., Cesaro, S., Esposito, S., Matino, D., Mazzucchelli, R. I., Molinari, Angelo Claudio, Mura, R., Notarangelo, L. D., Tagliaferri, A., Di Minno, G., Clerici, M., Ambaglio, C., Brigida Aru, A., Baldacci, E., Barillari, G., Basso, M., Bernasconi, S., Bertamino, M., Bertoni, E., Biasoli, C., Federica Biguzzi, E., Bonetti, E., Borchiellini, A., Bulgarelli, S., Cabibbo, S., Cantori, I., Castaman, G., Castiglia, P., Coluccia, A., Coppetelli, U., Coppola, A., Cultrera, D., De Candia, E., Delios, G., Di Gennaro, L., Di Gregorio, P., Di Minno, M., Dragani, A., Pietro Ettorre, C., Franchini, M., Galli, M., Gallo, G., Giordano, P., Giuffrida, G., Iannaccaro, P., Lassandro, G., Lazzareschi, I., Linari, S., Luciani, M., Macchi, S., Malcangi, G., Malizia, R., Marietta, M., Marino, R., Massoud, M., Gabriella Mazzucconi, M., Milan, M., Morfini, M., Napolitano, M., Pasca, S., Pedrazzi, P., Peyvandi, F. A., Piscitelli, L., Pollio, B., Preti, P., Quintavalle, G., Radossi, P., Raso, S., Ricca, I., Rocino, A., Santoro, C., Carlotta Santoro, R., Sarolo, L., Schiavoni, M., Schiavulli, M., Sciancalepore, P., Luisa Serino, M., Mario Siragusa, S., Sottilotta, G., Svahn, J., Valdre, L., Cristina Vedovati, M., and Zanon, E.

Subjects
Adult, medicine.medical_specialty, Consensus, Delphi Technique, Vaccination schedule, Delphi method, haemophilia, 030204 cardiovascular system & hematology, Hemophilia A, Haemophilia, immunization, Hemophilia B, bleeding disorder, factor VIII inhibitor, vaccination, Child, Evidence-Based Medicine, Humans, Italy, Vaccination, 03 medical and health sciences, 0302 clinical medicine, Vaccine administration, Medicine, In patient, Clinical Haemophilia, Genetics (clinical), business.industry, Original Articles, Hematology, General Medicine, Evidence-based medicine, medicine.disease, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Immunization, Family medicine, Original Article, business, 030215 immunology
Abstract

Vaccination against communicable diseases is crucial for disease prevention, but this practice poses challenges to healthcare professionals in patients with haemophilia. Poor knowledge of the vaccination requirements for these patients and safety concerns often result in vaccination delay or avoidance. In order to address this issue, a panel of 11 Italian haemophilia and immunization experts conducted a Delphi consensus process to identify the main concerns regarding the safe use of vaccines in patients with haemophilia. The consensus was based on a literature search of the available evidence, which was used by the experts to design 27 consensus statements. A group of clinicians then rated these statements using the 5‐point Likert‐type scale (1 = strongly disagree; 5 = strongly agree). The main issues identified by the expert panel included vaccination schedule for haemophilic patients; protocol and optimal route of vaccine administration; vaccination of haemophilic patients with antibodies inhibiting coagulation factor VIII (inhibitors); and vaccination and risk of inhibitor development. This manuscript discusses these controversial areas in detail supported by the available literature evidence and provides evidence‐ and consensus‐based recommendations. Overall, participants agreed on most statements, except those addressing the potential role of vaccination in inhibitor formation. Participants agreed that patients with haemophilia should receive vaccinations according to the institutional schedule for individuals without bleeding disorders; however, vaccination of patients with haemophilia requires comprehensive planning, taking into account disease severity, type and route of vaccination, and bleeding risk. Data also suggest vaccination timing does not need to take into consideration when the patient received factor VIII replacement.

Published
2019

8. Heparin induced thrombocytopenia: position paper from the Italian Society on Thrombosis and Haemostasis (SISET)

Author

Marcucci, R., Berteotti, M., Gori, A. M., Giusti, B., Rogolino, A. A., Sticchi, E., Liotta, A. A., Ageno, W., De Candia, E., Gresele, P., Marchetti, M., Marietta, M., and Tripodi, A.

Subjects
Platelets, platelets, thrombocytopenia, heparin, argatroban, danaparoid, fondaparinux, Heparin, Settore MED/09 - MEDICINA INTERNA, Anticoagulants, Disease Management, Thrombocytopenia, Argatroban, Haemostasis and Thrombosis, Fondaparinux, Italy, Danaparoid, Humans, Societies, Medical
Abstract

Heparin induced thrombocytopenia (HIT) is a rare immune mediated adverse drug reaction occurring after exposure to heparin. It is a serious and potentially fatal condition, which may be associated with the development of arterial or venous thrombotic events. Although known for many years, HIT is still often misdiagnosed. Pre- test clinical probability, screening for anti-PF4/heparin antibodies and documentation of their platelet activating capacity are the cornerstones of diagnosis. However, both clinical algorithms and test modalities have limited predictive values and limited diffusion so that the diagnosis and management is challenging in the clinical practice. For this reason, there is an unmet need for novel rational non-anticoagulant therapies based on the pathogenesis of HIT. The present paper reports the position of the Italian Society on Haemostasis and Thrombosis (SISET) in order to increase awareness of HIT among clinicians and other health care professionals and to provide information on the most appropriate management.

Published
2020

9. Validation of the ISTH/SSC bleeding assessment tool for inherited platelet disorders: A communication from the Platelet Physiology SSC

Author

Gresele P, Orsini S, Noris P, Falcinelli E, Alessi MC, Bury L, Borhany M, Santoro C, Glembotsky AC, Cid AR, Tosetto A, De Candia E, Fontana P, Guglielmini G, Pecci A, and BAT-VAL study investigators

Subjects
bleeding assessment tool, bleeding diathesis, bleeding disorders, inherited platelet disorders, platelets
Abstract

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.

Published
2020

15. Thromboelastography clot strength profiles and effect of systemic anticoagulation in COVID-19 acute respiratory distress syndrome: a prospective, observational study.

Author

BOCCI, M. G., MAVIGLIA, R., CONSALVO, L. M., GRIEGO, D. L., MONTINI, L., MERCURIO, G., NARDI, G., PISAPIA, L., CUTULI, S. L., BIASUCCI, D. G., GORI, C., ROSENKRANZ, R., DE CANDIA, E., CARELLI, S., NATALINI, D., ANTONELLI, M., and FRANCESCHI, F.

Abstract

OBJECTIVE: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection may yield a hypercoagulable state with fibrinolysis impairment. We conducted a single-center observational study with the aim of analyzing the coagulation patterns of intensive care unit (ICU) COVID-19 patients with both standard laboratory and viscoelastic tests. The presence of coagulopathy at the onset of the infection and after seven days of systemic anticoagulant therapy was investigated. PATIENTS AND METHODS: Forty consecutive SARS-CoV-2 patients, admitted to the ICU of a University hospital in Italy between 29th February and 30th March 2020 were enrolled in the study, providing they fulfilled the acute respiratory distress syndrome criteria. They received full-dose anticoagulation, including Enoxaparin 0.5 mg⋅kg-1 subcutaneously twice a day, unfractionated Heparin 7500 units subcutaneously three times daily, or low-intensity Heparin infusion. Thromboelastographic (TEG) and laboratory parameters were measured at admission and after seven days. RESULTS: At baseline, patients showed elevated fibrinogen activity [rTEG-Ang 80.5° (78.7 to 81.5) ; TEG-ACT 78.5 sec (69.2 to 87.9)] and an increase in the maximum amplitude of clot strength [FF-MA 42.2 mm (30.9 to 49.2)]. No alterations in time of the enzymatic phase of coagulation [CKH-K and CKH-R, 1.1 min (0.85 to 1.3) and 6.6 min (5.2 to 7.5), respectively] were observed. Absent lysis of the clot at 30 minutes (LY30) was observed in all the studied population. Standard coagulation parameters were within the physiological range: [INR 1. 09 (1.01 to 1.20), aPTT 34.5 sec (29.7 to 42.2), antithrombin 97.5% (89.5 to 115)]. However, plasma fibrinogen [512.5 mgdl-1 (303.5 to 605)], and D-dimer levels [1752.5 ngml-1 (698.5 to 4434.5)], were persistently increased above the reference range. After seven days of full-dose anticoagulation, average TEG parameters were not different from baseline (rTEG-Ang p = 0.13, TEG-ACT p = 0.58, FF-MA p = 0.24, CK-R p = 0.19, CKH-R p = 0.35), and a persistent increase in white blood cell count, platelet count and D-dimer was observed (white blood cell count p < 0.01, neutrophil count p = 0.02, lymphocyte count p < 0.01, platelet count p = 0.13 < 0.01, D-dimer levels p= 0.02). CONCLUSIONS: SARS-CoV-2 patients with acute respiratory distress syndrome show elevated fibrinogen activity, high D-dimer levels and maximum amplitude of clot strength. Platelet count, fibrinogen, and standard coagulation tests do not indicate a disseminated intravascular coagulation. At seven days, thromboelasto-graphic abnormalities persist despite full-dose anticoagulation. [ABSTRACT FROM AUTHOR]

Published
2020

16. Bleeding risk of surgery and its prevention in patients with inherited platelet disorders

Author

Orsini, S, Noris, P, Bury, L, Heller, PG, Santoro, C, Kadir, RA, Butta, NC, Falcinelli, E, Cid, AR, Fabris, F, Fouassier, M, Miyazaki, K, Lozano, ML, Zúñiga P, Flaujac, C, Podda, GM, Bermejo, N, Favier, R, Henskens, Y, De Maistre, E, De Candia, E, Mumford, AD, Ozdemir, GN, Eker, I, Nurden, P, Bayart, S, Lambert, MP, Bussel, J, Zieger, B, Tosetto, A, Melazzini, F, Glembotsky, AC, Pecci, A, Cattaneo, M, Schlegel, N, Gresele, P, and European Hematology Association - Scientific Working Group (EHA-SWG) on thromboc

Abstract

Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders. However, very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a worldwide, multicentric, retrospective study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted, and their efficacy in patients with inherited platelet disorders: the Surgery in Platelet disorders And Therapeutic Approach (SPATA) study. We rated the outcome of 829 surgical procedures carried out in 423 patients with well-defined forms of inherited platelet disorders: 238 inherited platelet function disorders and 185 inherited platelet number disorders. Frequency of surgical bleeding was high in patients with inherited platelet disorders (19.7%), with a significantly higher bleeding incidence in inherited platelet function disorders (24.8%) than in inherited platelet number disorders (13.4%). The frequency of bleeding varied according to the type of inherited platelet disorder, with biallelic Bernard Soulier syndrome having the highest occurrence (44.4%). Frequency of bleeding was predicted by a pre-operative World Health Organization bleeding score of 2 or higher. Some types of surgery were associated with a higher bleeding incidence, like cardiovascular and urological surgery. The use of pre-operative pro-hemostatic treatments was associated with a lower bleeding frequency in patients with inherited platelet function disorders but not in inherited platelet number disorders. Desmopressin, alone or with antifibrinolytic agents, was the preventive treatment associated with the lowest bleedings. Platelet transfusions were used more frequently in patients at higher bleeding risk. Surgical bleeding risk in inherited platelet disorders is substantial, especially in inherited platelet function disorders, and bleeding history, type of disorder, type of surgery and female sex are associated with higher bleeding frequency. Prophylactic pre-operative pro-hemostatic treatments appear to be required and are associated with a lower bleeding incidence.

Published
2017

18. MYH9-Related Disease: A Novel Prognostic Model to Predict the Clinical Evolution of the Disease Based on Genotype-Phenotype Correlations

Author

Pecci, A, Klersy, C, Gresele, P, Lee, K, De Rocco, D, Bozzi, V, Russo, G, Heller, Pg, Loffredo, G, Ballmaier, M, Fabris, F, Beggiato, E, Kahr, Wha, Pujol-Moix, N, Platokouki, H, Matthijs, G, Noris, P, Yerram, P, Hermans, C, Batzios, S, De Groot, M, Zieger, B, De Candia, E, Fraticelli, V, Kersseboom, R, Piccoli, Gb, Zimmermann, S, Zaninetti, C, Nicchia, E, Baronci, C, Seri, M, Knight, Pj, Balduini, Cl, Savoia, A, Van Geet, C, Geber, B, Economou, M, Fierro, T, Glembotsky, Ac, Vianello, F, Guthner, C., Pecci, A, Klersy, C, Gresele, P, Lee, Kj, De Rocco, D, Bozzi, V, Russo, G, Heller, Pg, Loffredo, G, Ballmaier, M, Fabris, F, Beggiato, E, Kahr, Wh, Pujol-Moix, N, Platokouki, H, Van Geet, C, Noris, P, Yerram, P, Hermans, C, Gerber, B, Economou, M, De Groot, M, Zieger, B, De Candia, E, Fraticelli, V, Kersseboom, R, Piccoli, Gb, Zimmermann, S, Fierro, T, Glembotsky, Ac, Vianello, F, Zaninetti, C, Nicchia, E, Güthner, C, Baronci, C, Seri, M, Knight, Pj, Balduini, Cl, Savoia, A., DE ROCCO, Daniela, Pujol Moix, N, Nicchia, Elena, Savoia, Anna, and University of Zurich

Subjects
Male, Oncology, thrombocytopenia, Medicina Clínica, Disease, Malattia MYH9 associata, Myh9 related disease, MYH9 RELATED DISEASE, Myh9, MYH9, Risk Factors, purl.org/becyt/ford/3.2 [https], Genotype, Genetics(clinical), CRYSTAL-STRUCTURE, Age of Onset, IIA, Genetics (clinical), deafne, MYOSIN HEAVY-CHAIN, EPSTEIN-SYNDROME, Molecular Motor Proteins, FECHTNER SYNDROMES, Trombocitopenia, Penetrance, POWER STROKE STATE, Phenotype, Italy, nephropathy, Female, purl.org/becyt/ford/3 [https], Miosina No Muscular Iia, Adult, 2716 Genetics (clinical), medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, MOTOR DOMAIN, Hearing Loss, Sensorineural, Genetic counseling, 610 Medicine & health, Biology, nonmuscle myosin, Article, Cataract, Nephropathy, 1311 Genetics, Internal medicine, deafness, Genetics, medicine, Humans, Hematología, Gene, Genetic Association Studies, Hereditaria, Myosin Heavy Chains, MUTATIONS, Settore MED/09 - MEDICINA INTERNA, medicine.disease, Amino Acid Substitution, Epstein Syndrome, Mutation, 10032 Clinic for Oncology and Hematology, Linear Models, SMOOTH-MUSCLE MYOSIN
Abstract

MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9-RD is characterized by a considerable variability in clinical evolution: patients present at birth with only thrombocytopenia, but some of them subsequently develop sensorineural deafness, cataract, and/or nephropathy often leading to end-stage renal disease (ESRD). We searched for genotype–phenotype correlations in the largest series of consecutive MYH9-RD patients collected so far (255 cases from 121 families). Association of genotypes with noncongenital features was assessed by a generalized linear regression model. The analysis defined disease evolution associated to seven different MYH9 genotypes that are responsible for 85% of MYH9-RD cases. Mutations hitting residue R702 demonstrated a complete penetrance for early-onset ESRD and deafness. The p.D1424H substitution associated with high risk of developing all the noncongenital manifestations of disease. Mutations hitting a distinct hydrophobic seam in the NMMHC-IIA head domain or substitutions at R1165 associated with high risk of deafness but low risk of nephropathy or cataract. Patients with p.E1841K, p.D1424N, and C-terminal deletions had low risk of noncongenital defects. These findings are essential to patients' clinical management and genetic counseling and are discussed in view of molecular pathogenesis of MYH9-RD. Fil: Pecci, Alessandro. University of Pavia; Italia Fil: Klersy, Catherine. IRCCS Policlinico San Matteo Foundation; Italia Fil: Gresele, Paolo. Università di Perugia; Italia Fil: Lee, Kieran J. D.. University of Leeds; Reino Unido Fil: De Rocco, Daniela. Università degli Studi di Trieste; Italia Fil: Bozzi, Valeria. University of Pavia; Italia Fil: Russo, Giovanna. University of Catania; Italia Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Loffredo, Giuseppe. Pausilipon Hospital. Department of Oncology; Italia Fil: Ballmaier, Matthias. Hannover Medical School; Alemania Fil: Fabris, Fabrizio. Università di Padova; Italia Fil: Beggiato, Eloise. Hospital “Città della Salute e Della Scienza”; Italia Fil: Kahr, Walter H. A.. University of Toronto; Canadá. Hospital for Sick Children. Division of Hematology/Oncology; Canadá Fil: Pujol Moix, Nuria. Universitat Autònoma de Barcelona; España Fil: Platokouki, Helen. “Aghia Sophia” Children's Hospital; Grecia Fil: Van Geet, Christel. University of Leuven. Center for Molecular and Vascular Biology; Bélgica Fil: Noris, Patrizia. University of Pavia; Italia Fil: Yerram, Preethi. University of Missouri; Estados Unidos Fil: Hermans, Cedric. St-Luc University Hospital; Bélgica Fil: Gerber, Bernhard. University Hospital Zurich, Division of Hematology; Suiza Fil: Economou, Marina. Aristotle University; Grecia Fil: De Groot, Marco. University of Groningen; Países Bajos Fil: Zieger, Barbara. University Medical Center Freiburg; Alemania Fil: De Candia, Erica. Catholic University of Rome; Italia Fil: Fraticelli, Vincenzo. Giovanni Paolo II Foundation; Italia Fil: Kersseboom, Rogier. Erasmus Medical Centre; Países Bajos Fil: Piccoli, Giorgina B.. Università di Torino; Italia Fil: Zimmermann, Stefanie. Goethe Universitat Frankfurt; Alemania Fil: Fierro, Tiziana. Università di Perugia; Italia Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Vianello, Fabrizio. Università di Padova; Italia Fil: Zaninetti, Carlo. University of Pavia; Italia Fil: Nicchia, Elena. Università degli Studi di Trieste; Italia Fil: Güthner, Christiane. Stadtspital Triemli. Department of Medical Oncology and Hematology; Italia Fil: Baronci, Carlo. Pediatric Hospital "Bambino Gesù"; Italia Fil: Seri, Marco. Università di Bologna; Italia Fil: Knight, Peter J.. University of Leeds; Reino Unido Fil: Balduini, Carlo L.. University of Pavia; Italia Fil: Savoia, Anna. Università degli Studi di Trieste; Italia

Published
2014

20. Efficacy and Safety of Low-Dose Aspirin in Polycythemia Vera

Author

Landolfi, R, Marchioli, R, Kutti, J, Gisslinger, H, Tognoni, G, Patrono, C, Barbui, T, Finazzi, G, Pusterla, S, Falanga, A, Galli, M, Wadenvik, H, Gastl, G, Ludescher, C, Lutz, D, Girschikofsky, M, Michlmayr, G, Rechberger, E, Niessner, H, Ivansich, E, Rain, Jd, Chommienne Thomas, C, Hehlmann, R, Engelich, G, Kohne, E, Kramer, A, Christakis, Ji, Papaioannou, M, Gerotziafas, G, O'Donnell, R, Bennett, M, Lugassy, G, Ellis, M, Eldor, A, Naparstek, E, Marilus, R, Leoni, P, Rupoli, S, Scortechini, Ar, Agostini, V, Volpe, E, Calmieri, F, Volpe, A, Storti, G, Ciampa, A, Dammacco, F, Lauta, Vm, Ranieri, G, Rizzi, R, Orsola, S, Tura, S, Finelli, C, Marino, G, Rossi, G, Almici, C, Capucci, A, Zanetti, F, Giustolisi, R, Cacciola, Rr, Cacciola, E, Peta, A, Magro, D, Frigerio, G, Alberio, F, Beretta, A, Bonferroni, M, Raviolo, A, Ferrini, Prl, Grossi, A, Fabbri, A, Nardelli, S, Centra, A, Musolino, C, Bellomo, G, Trincali, O, Spatari, Giovanna, Foa, P, Gerli, G, Carraro, Mc, Zanella, A, Lurlo, A, Barraco, F, Torelli, G, Marietta, M, Pogliani, E, Miccolis, Ir, La Rocca, A, Puglisi, A, Sardeo, G, Rotoli, B, Martinelli, V, Ciancia, R, Cardarelli, A, Cimino, R, Fasanaro, A, Randi, Ml, Rizzoli, V, Caramatti, C, Gaeta, L, Lazzarino, M, Passamonti, F, Lazzola, M, Malabarba, L, Natale, D, Pulini, S, Davi, G, Gugliotta, L, Ilariucci, F, De Candia, E, Eugenio, S, Amadori, S, Buccisano, F, Mandelli, F, Montefusco, E, Petti, Mc, Spadea, A, Carotenuto, M, Morelli, A, Nobile, M, Longinotti, M, Pardini, Sm, Lauria, F, Buccalossi, A, Gentili, S, Mazza, P, Cervellera, M, Maggi, A, Di Francesco, A, Pasqualoni, E, Chisesi, T, Polacco, A, Capnist, G, Rodeghiero, F, Ruggeri, M, Arrizabalaga, B, Remacha, A, De Mendiguren, Bp, Hernandez Nieto, L, Hernandez Garcia, Mt, Gonzalez Brito, G, Machado, P, Garcia, G, Villegas, A, Pena, A, Fernandez, Ag, Carbonell, F, Del Arco, A, Back, H, Stenke, L, Hansen, S, Larsson, G, Stromblad, G, Lauri, B, Ryden, Bo, Linder, O, Lundholm, Bg, Lannemyr, O, Strandberg, M, Andreasson, B, Stockelberg, D, Pasquariello, F, Tichelli, A, Otremba, B, Hinrichs, Hf, Weber Stadelmann, W, Bareford, D, Oscier, Dg, Bowey, N, Taylor, Pc, de Gaetano, G, Najean, Y, Pearson, Tc, Di Blasio, A, Atashkar, S, Mari, E, Tamayo, D, Borelli, G, Ferri, B, Marfisi, Rm, Olivieri, M, Polidoro, A, Spoltore, R, Levantesi, G, Di Mascio, R, Miceli, G, Sperti, G, Correale, E, Vermjlen, J, and Collins, R.

Subjects
Aspirin, medicine.medical_specialty, business.industry, food and beverages, General Medicine, medicine.disease, Thrombosis, Pulmonary embolism, Venous thrombosis, Polycythemia vera, Relative risk, Internal medicine, Anesthesia, Cardiology, Medicine, Myocardial infarction, business, Contraindication, medicine.drug
Abstract

background The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial. methods We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and no contraindication to such treatment in a double-blind, placebo-controlled, randomized trial to assess the safety and efficacy of prophylaxis with low-dose aspirin (100 mg daily). The two primary end points were the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The mean duration of follow-up was about three years. results Treatment with aspirin, as compared with placebo, reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality were not reduced significantly. The incidence of major bleeding episodes was not significantly increased in the aspirin group (relative risk, 1.62; 95 percent confidence interval, 0.27 to 9.71). conclusions Low-dose aspirin can safely prevent thrombotic complications in patients with polycythemia vera who have no contraindications to such treatment.

Published
2004

22. Cardiovascular risk and inflammation in nonalcoholic fatty liver disease: The upregulation of inflammatory platelet transcripts suggest a role for platelets in the “inflammatory network” of NAFLD

Author

Alberelli, M.A., primary, Miele, L., additional, Racco, S., additional, Biolato, M., additional, Marrone, G., additional, Cefalo, C., additional, Landolfi, R., additional, Gasbarrini, A., additional, De Candia, E., additional, and Grieco, A., additional

Published
2015
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34. The Asp(272)-Glu(282) region of platelet glycoprotein Ibalpha interacts with the heparin-binding site of alpha-thrombin and protects the enzyme from the heparin-catalyzed inhibition by antithrombin III.

Author

De Cristofaro, R, De Candia, E, Rutella, S, and Weitz, J I

Abstract

Platelet glycoprotein Ib (GpIb) mediates interaction with both von Willebrand factor and thrombin. Thrombin binds to GpIb via its heparin-binding site (HBS) (De Candia, E., De Cristofaro, R., De Marco, L., Mazzucato, M., Picozzi, M., and Landolfi, R. (1997) Thromb. Haemostasis 77, 735-740; De Cristofaro, R., De Candia, E., Croce, G., Morosetti, R., and Landolfi, R. (1998) Biochem. J. 332, 643-650). To identify the thrombin-binding domain on GpIbalpha, we examined the effect of GpIbalpha(1-282), a GpIbalpha fragment released by the cobra venom mocarhagin on the heparin-catalyzed rate of thrombin inhibition by antithrombin III (AT). GpIbalpha(1-282) inhibited the reaction in a dose-dependent and competitive fashion. In contrast, the GpIbalpha(1-271) fragment, produced by exposing GpIbalpha(1-282) to carboxypeptidase Y, had no effect on thrombin inhibition by the heparin-AT complex. Measurements of the apparent equilibrium constant of the GpIbalpha(1-282) binding to thrombin as a function of different salts (NaCl and tetramethyl-ammonium chloride) concentration (0.1-0.2 M) indicated a large salt dependence (Gamma(+/-) = -4.5), similar to that pertaining to the heparin binding to thrombin. The importance of thrombin HBS in its interaction with GpIbalpha was confirmed using DNA aptamers, which specifically bind to either HBS (HD22) or the fibrinogen recognition site of thrombin (HD1). HD22, but not HD1, inhibited thrombin binding to GpIbalpha(1-282). Furthermore, the proteolytic derivative gamma(T)-thrombin, which lacks the fibrinogen recognition site, binds to GpIbalpha via its intact HBS in a reaction that is inhibited by HD22. Neither alpha- nor gamma(T)-thrombin bound to GpIbalpha(1-271), suggesting that the Asp(272)-Glu(282) region of GpIbalpha may act as a "heparin-like" ligand for the thrombin HBS, thereby inhibiting heparin binding to thrombin. It was also demonstrated that intact platelets may dose-dependently inhibit the heparin-catalyzed thrombin inhibition by AT at enzyme concentrations <5 nM. Altogether, these findings show that thrombin HBS binds to the region of GpIbalpha involving the Asp(272)-Glu(282) segment, protecting the enzyme from the inactivation by the heparin-AT system.

Published
2000

35. Allosteric equilibria in the binding of fibrinogen to platelets.

Author

De Cristofaro, R, Landolfi, R, De Candia, E, Castagnola, M, Di Cera, E, and Wyman, J

Abstract

The binding of fibrinogen to platelets occurs according to the law of mass action. The platelet receptor binds reversibly a single fibrinogen molecule and undergoes a conformational transition between two allosteric states, T and R, that differ in their affinity for fibrinogen. The equilibrium between the two forms is shifted by ADP toward the R (high-affinity) state, thus promoting the aggregation process. This model opens the way to consideration of allosteric modulation of the binding of fibrinogen to its platelet receptor.

Published
1988
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36. Increased platelet-fibrinogen affinity in patients with myeloproliferative disorders [see comments]

Author

Landolfi, R, De Cristofaro, R, Castagnola, M, De Candia, E, D'Onofrio, G, Leone, G, and Bizzi, B

Abstract

Patients with myeloproliferative disorders (MPD) are known to have some abnormalities of platelet glycoproteins (Gp). Quantitative changes of the Gp Ib, IIb-IIIa, and/or their glucidic content have been reported. Since the Gp IIb-IIIa complex plays a major role in fibrinogen binding by activated platelets, we measured the platelet fibrinogen affinity in nine patients with polycythemia vera (PV) and one subject with chronic myeloid leukemia (CML) by the aggregometric method of Marguerie. In all patients the Kd of the platelet fibrinogen reaction was significantly decreased as compared to controls, with evidence in two cases with PV of a heterogeneity of platelet-fibrinogen receptor sites. The measurement of 125I-labeled fibrinogen-platelet binding, performed in seven patients (five PV and two CML), showed receptor populations with increased (Kd1 = 0.58 + 0.3 X 10(7) mol/L) and normal affinity (Kd2 = 5.12 + 3.1 X 10(7) mol/L). These results demonstrate a heterogeneity of platelet-fibrinogen receptors in these patients and may explain the thrombotic diathesis of MPD subjects.

Published
1988
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40. Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history of MYH9-related disease

Author

Nuria Pujol-Moix, Carmine Pecoraro, Paula G. Heller, Paolo Gresele, Filomena Di Bari, Carlo Dufour, Erica De Candia, Michael Doubek, Patrizia Noris, Pasi A. Koivisto, Marco Seri, Stefan Lethagen, Patrizia Alvisi, Umberto Russo, Carlo L. Balduini, Ugo Ramenghi, Achille Iolascon, Dirk Schwabe, Valeria Bozzi, Anna Savoia, Alessandro Pecci, Bianca Rocca, Catherine Klersy, Antonio Granata, Emanuele Panza, Fabrizio Fabris, Pecci A, Panza E, Pujol-Moix N, Klersy C, Di Bari F, Bozzi V, Gresele P, Lethagen S, Fabris F, Dufour C, Granata A, Doubek M, Pecoraro C, Koivisto PA, Heller PG, Iolascon A, Alvisi P, Schwabe D, De Candia E, Rocca B, Russo U, Ramenghi U, Noris P, Seri M, Balduini CL, Savoia A., Pecci, A, Panza, E, PUJOL MOIX, N, Klersy, C, DI BARI, F, Bozzi, V, Gresele, P, Lethagen, S, Fabris, F, Dufour, C, Granata, A, Doubek, M, Pecoraro, C, Koivisto, Pa, Heller, Pg, Iolascon, A, Alvisi, P, Schwabe, D, DE CANDIA, E, Rocca, B, Russo, U, Ramenghi, U, Noris, P, Seri, M, Balduini, Cl, Savoia, Anna, Pujol Moix, N, Di Bari, F, Iolascon, Achille, De Candia, E, and Savoia, A.

Subjects
Male, sindrome di Fechtner, Presenile cataracts, MYH9-RELATED DISEASE, Kaplan-Meier Estimate, Medicina Clínica, anomalia di May-Hegglin, medicine.disease_cause, Gastroenterology, MYH9, Sebastian syndrome, MUTATION, Genetics (clinical), gene MYH9, Genes, Dominant, Genetics, Mutation, Nephritis, sindrome di Sebastian, Fechtner syndrome, Molecular Motor Proteins, Syndrome, Middle Aged, Phenotype, Female, Adult, medicine.medical_specialty, May-Hegglin anomaly, CIENCIAS MÉDICAS Y DE LA SALUD, Genotype, Hearing Loss, Sensorineural, Biology, Cataract, nonmuscle myosin IIA, miosina nonmuscolare IIA, sindrome di Epstein, Cataracts, Internal medicine, medicine, Humans, Hematología, Survival analysis, INHERITED THROMBOCYTOPENIA, Myosin Heavy Chains, Platelet Count, Infant, medicine.disease, Thrombocytopenia, Protein Structure, Tertiary, Epstein Syndrome, MYH9 GENE, Epstein syndrome, May–Hegglin anomaly
Abstract

MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness, presenile cataracts, and/or progressive nephritis leading to end-stage renal failure. No consistent correlations have been identified between the 27 different MYH9 mutations identified so far and the variable clinical evolution of the disease.We have evaluated 108 consecutive MYH9- RD patients belonging to 50 unrelated pedigrees. The risk of noncongenital manifestations associated with different genotypes was estimated over time by event-free survival analysis.We demonstrated that all subjects with mutations in the motor domain of NMMHC-IIA present with severe thrombocytopenia and develop nephritis and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. We also evaluated the clinical course of patients with mutations in the four most frequently affected residues of NMMHC-IIA (responsible for 70% of MYH9-RD cases).We concluded that mutations at residue 1933 do not induce kidney damage or cataracts and cause deafness only in the elderly, those in position 702 result in severe thrombocytopenia and produce nephritis and deafness at a juvenile age, while alterations at residue 1424 or 1841 result in intermediate clinical pictures. These findings are relevant not only to patients’ clinical management but also to the elucidation of the pathogenesis of the disease. Fil: Pecci, Alessandro. Universita Degli Studi Di Pavia; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Panza, Emanuele. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Universidad de Bologna; Italia Fil: Pujol Moix, Núria. Hospital de la Santa Creu i Sant Pau; España Fil: Klersy, Catherine. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Di Bari, Filomena. Telethon Institute of Genetics and Medicine; Italia Fil: Bozzi, Valeria. Universita Degli Studi Di Pavia; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Gresele, Paolo. Università di Perugia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Lethagen, Stefan. Universidad de Copenhagen; Dinamarca. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Fabris, Fabrizio. Università di Padova; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Dufour, Carlo. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Granata, Antonio. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Policlinico "Vittorio Emanuele"; Italia Fil: Doubek, Michael. University Hospital; República Checa Fil: Pecoraro, Carmine. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. ‘‘Santobono’’ Children’s Hospital; Italia Fil: Koivisto, Pasi A.. Tampere University Hospital; Finlandia Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Iolascon, Achille. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Università degli Studi di Napoli Federico II; Italia Fil: Alvisi, Patrizia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Ospedale Maggiore Carlo Alberto Pizzardi; Italia Fil: Schwabe, Dirk. Goethe Universitat Frankfurt; Alemania Fil: De Candia, Erica. Università degli studi di Roma "La Sapienza"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Rocca, Bianca. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Università degli studi di Roma "La Sapienza"; Italia Fil: Russo, Umberto. Ospedale Luigi Sacco; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Ramenghi, Ugo. Università degli studi di Torino; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Noris, Patrizia. Universita Degli Studi Di Pavia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia Fil: Seri, Marco. Universidad de Bologna; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Balduini, Carlo L.. Universita Degli Studi Di Pavia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia Fil: Savoia, Anna. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia

Published
2008

41. Rituximab for treatment of autoimmune acquired platelet function disorders: description of two cases of acquired Glanzmann thrombasthenia and one case of acquired delta storage pool disease

Author

Maria Adele Alberelli, Marina Marchetti, Anna Falanga, Raffaele Landolfi, Paola Ferrazzi, Corrado Lodigiani, Alfredo Dragani, Sara Gamba, Erica De Candia, Monica Bacci, Alberelli, M, Bacci, M, Marchetti, M, Ferrazzi, P, Dragani, A, Gamba, S, Landolfi, R, Falanga, A, Lodigiani, C, and De Candia, E

Subjects
Adult, Male, Albinism, acquired platelet function disorders, acquired platelet function disorders, delta storage pool disease, Glanzmann thrombasthenia, immune-mediated platelet disorder, rituximab, Hemorrhagic Disorders, Glanzmann thrombasthenia, delta storage pool disease, immune-mediated platelet disorder, rituximab, Autoimmune Diseases, medicine, Humans, Platelet, Delta storage pool disease, Aged, Platelet Count, business.industry, Settore MED/09 - MEDICINA INTERNA, Hematology, Hermanski-Pudlak Syndrome, Immunology, Female, Rituximab, business, Immunosuppressive Agents, Thrombasthenia, medicine.drug
Published
2019

42. Platelet diameters in inherited thrombocytopenias: analysis of 376 patients with all known disorders

Author

Erica De Candia, Claudia Cagioni, Nuria Pujol-Moix, Valeria Bozzi, Marco Cattaneo, Federica Melazzini, Carlo L. Balduini, Alessandro Pecci, James B. Bussel, Patrizia Noris, Fabrizio Fabris, Giuseppe Loffredo, Ginevra Biino, Marco Seri, Lucia Dora Notarangelo, Giovanna Russo, Paula G. Heller, Paolo Gresele, Anna Savoia, Elisa Civaschi, Ugo Ramenghi, Serena Barozzi, Shinji Kunishima, Noris, P, Biino, G, Pecci, A, Civaschi, E, Savoia, Anna, Seri, M, Melazzini, F, Loffredo, G, Russo, G, Bozzi, V, Notarangelo, Ld, Gresele, P, Heller, Pg, Pujol Moix, N, Kunishima, S, Cattaneo, M, Bussel, J, De Candia, E, Cagioni, C, Ramenghi, U, Barozzi, S, Fabris, F, Balduini, Cl, P. Nori, G. Biino, A. Pecci, E. Civaschi, A. Savoia, M. Seri, F. Melazzini, G. Loffredo, G. Russo, V. Bozzi, L. D. Notarangelo, P. Gresele, P. G. Heller, N. Pujol-Moix, S. Kunishima, M. Cattaneo, J. Bussel, E. De Candia, C. Cagioni, U. Ramenghi, S. Barozzi, F. Fabri, and C. L. Balduini

Subjects
Male, MYH9-RELATED DISEASE, PLAQUETAS, Medicina Clínica, PHENOTYPE, Biochemistry, chemistry.chemical_compound, hemic and lymphatic diseases, purl.org/becyt/ford/3.2 [https], IMMUNE THROMBOCYTOPENIA, ELTROMBOPAG, MUTATIONS, PURPURA, ADULTS, Platelet, inherited thrombocytopenia, Child, inherited thrombocytopenias, TROMBOCITOPENIAS, Molecular Motor Proteins, Hematology, Middle Aged, platelet size, Child, Preschool, Abnormalities of platelet size, Female, purl.org/becyt/ford/3 [https], DPM, Adult, Blood Platelets, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Adolescent, Hearing Loss, Sensorineural, Platelet disorder, Immunology, Eltrombopag, PLATELET DISORDERS, Diagnosis, Differential, Young Adult, Internal medicine, medicine, Humans, Hematología, Mean platelet volume, Cell Size, Purpura, Thrombocytopenic, Idiopathic, Platelet diameter, Myosin Heavy Chains, business.industry, THROMBOCYTOPENIA, Large Platelets, Infant, Cell Biology, Platelets and Thrombopoiesis, Immune thrombocytopenia, Settore MED/15 - MALATTIE DEL SANGUE, Endocrinology, Giant platelets, chemistry, Case-Control Studies, Mutation, business
Abstract

Abnormalities of platelet size are one of the distinguishing features of inherited thrombocytopenias (ITs), and evaluation of blood films is recommended as an essential step for differential diagnosis of these disorders. Nevertheless, what we presently know about this subject is derived mainly from anecdotal evidence. To improve knowledge in this field, we evaluated platelet size on blood films obtained from 376 patients with all 19 forms of IT identified so far and found that these conditions differ not only in mean platelet diameter, but also in platelet diameter distribution width and the percentage of platelets with increased or reduced diameters. On the basis of these findings, we propose a new classification of ITs according to platelet size. It distinguishes forms with giant platelets, with large platelets, with normal or slightly increased platelet size, and with normal or slightly decreased platelet size. We also measured platelet diameters in 87 patients with immune thrombocytopenia and identified cutoff values for mean platelet diameter and the percentage of platelets with increased or reduced size that have good diagnostic accuracy in differentiating ITs with giant platelets and with normal or slightly decreased platelet size from immune thrombocytopenia and all other forms of IT. Fil: Noris, Patrizia. University of Pavia; Italia Fil: Biino, Ginevra. Consiglio Nazionale Delle Ricerche. Istituto di Genetica Molecolare; Italia Fil: Pecci, Alessandro. University of Pavia; Italia Fil: Civaschi, Elisa. University of Pavia; Italia Fil: Savoia, Anna. Università degli Studi di Trieste; Italia. Istituto Di Ricovero e Cura a Carattere Scientifico Burlo Garofolo; Italia Fil: Seri, Marco. Università di Bologna; Italia Fil: Melazzini, Federica. University of Pavia; Italia Fil: Loffreddo, Giuseppe. Pausilipon Hospital; Italia Fil: Russo, Giovana. Università degli Studi di Catania; Italia Fil: Bozzi, Valeria. University of Pavia; Italia Fil: Notarangelo, Lucia Dora. Spedali Civili. Ospedale dei Bambini; Italia Fil: Gresele, Paolo. Università di Perugia; Italia Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Pujol Moix, Nuria. Universitat Autònoma de Barcelona; España Fil: Kunishima, Shinji. National Hospital Organization Nagoya Medical Center; Japón Fil: Cattaneo, Marco. Università degli Studi di Milano; Italia Fil: Bussel, James. Cornell University; Estados Unidos Fil: de Candia, Erica. Universita Cattolica del Sacro Cuore; Italia Fil: Cagioni, Claudia. University of Pavia; Italia Fil: Ramenghi, Ugo. Università di Torino; Italia Fil: Barozzi, Serena. University of Pavia; Italia Fil: Fabris, Fabrizio. Università di Padova; Italia Fil: Balduini, Carlo L.. University of Pavia; Italia

Published
2014

43. Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia

Author

Paula G. Heller, Loredana Bury, Catherine Trichet, Nuria Pujol-Moix, Alessandro Pecci, Fabrizio Fabris, Maria Luigia Randi, Ana C. Glembotsky, Marco Cattaneo, Adam Cuker, Jeanne-Yvonne Borg, Nathalie Trillot, James B. Bussel, Patrizia Noris, E Muniz-Diaz, François Lanza, Lucia Dora Notarangelo, Dominique Martin-Coignard, Anne Bauters, Paolo Gresele, Thomas Lecompte, Catherine Klersy, Sandra Mercier, Giuseppe Loffredo, Marie-Françoise Hurtaud-Roux, Véronique Le Cam Duchez, Emanuela Falcinelli, Nicole Schlegel, Erica De Candia, Dino Veneri, Schéhérazade Benabdallah-Guedira, Fanny Menard, Catherine Pouymayou, Ilaria Nichele, Chloé James, Michela Faleschini, Elisa Civaschi, Caterina Marconi, Roberta Bottega, Tommaso Pippucci, Pierre Sié, Sophie Bayart, Béatrice Saposnik, Daniela De Rocco, Rémi Favier, Françoise Boehlen, Pierre Fontana, Alina Ferster, Anna Savoia, Carlo L. Balduini, Pamela Magini, Bruno Royer, Véronique Latger-Cannard, Alessandra Tucci, Dominique Fleury, Agnes Rigouzzo, Tiziana Fierro, Gian Marco Podda, Emmanuel de Maistre, Silvia Ferrari, Paquita Nurden, Pietro Minuz, Andreas Greinacher, Virginie Siguret, A. M. Mezzasoma, Patrizia, Nori, Nicole, Schlegel, Catherine, Klersy, Paula G., Heller, Elisa, Civaschi, Nuria Pujol, Moix, Fabrizio, Fabri, Remi, Favier, Paolo, Gresele, Véronique Latger, Cannard, Adam, Cuker, Paquita, Nurden, Andreas, Greinacher, Marco, Cattaneo, Erica De, Candia, Alessandro, Pecci, Marie Françoise Hurtaud, Roux, Ana C., Glembotsky, Eduardo Muñiz, Diaz, Maria Luigia, Randi, Nathalie, Trillot, Loredana, Bury, Thomas, Lecompte, Caterina, Marconi, Savoia, Anna, Carlo L., Balduini, Sophie, Bayart, Anne, Bauter, Schéhérazade Benabdallah, Guedira, Françoise, Boehlen, Jeanne Yvonne, Borg, Bottega, Roberta, James, Bussel, DE ROCCO, Daniela, Emmanuel de, Maistre, Faleschini, Michela, Emanuela, Falcinelli, Silvia, Ferrari, Alina, Ferster, Tiziana, Fierro, Dominique, Fleury, Pierre, Fontana, Chloé, Jame, Francois, Lanza, Véronique Le Cam, Duchez, Giuseppe, Loffredo, Pamela, Magini, Dominique Martin, Coignard, Fanny, Menard, Sandra, Mercier, Annamaria, Mezzasoma, Pietro, Minuz, Ilaria, Nichele, Lucia D., Notarangelo, Tommaso, Pippucci, Gian Marco, Podda, Catherine, Pouymayou, Agnes, Rigouzzo, Bruno, Royer, Pierre, Sie, Virginie, Siguret, Catherine, Trichet, Alessandra, Tucci, Béatrice, Saposnik, Dino, Veneri, Noris P, Schlegel N, Klersy C, Heller PG, Civaschi E, Pujol-Moix N, Fabris F, Favier R, Gresele P, Latger-Cannard V, Cuker A, Nurden P, Greinacher A, Cattaneo M, De Candia E, Pecci A, Hurtaud-Roux MF, Glembotsky AC, Muñiz-Diaz E, Randi ML, Trillot N, Bury L, Lecompte T, Marconi C, Savoia A, and Balduini CL

Subjects
Pediatrics, Blood transfusion, medicine.medical_treatment, PLAQUETAS, Medicina Clínica, Retrospective Studie, Pregnancy, purl.org/becyt/ford/3.2 [https], inherited thrombocytopenia, Young adult, ddc:616, education.field_of_study, Hematology, Medicine (all), TROMBOCITOPENIA, Articles, platelets, purl.org/becyt/ford/3 [https], Female, Medicina Critica y de Emergencia, Human, Adult, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Population, Humans, Infant, Newborn, Pregnancy Complications, Hematologic, Retrospective Studies, Thrombocytopenia, Young Adult, NO, bleeding risk, Hematologic, Internal medicine, medicine, education, Fetus, Hysterectomy, business.industry, Inherited thrombocytopenias, DIÁMETRO PLAQUETARIO, Infant, Retrospective cohort study, pregnancy, medicine.disease, Newborn, Pregnancy Complications, Settore MED/15 - MALATTIE DEL SANGUE, HEREDITARIA, business
Abstract

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 × 10(9)/L. Fil: Noris, Patrizia. Istituti di Ricovero e Cura a Carattere Scientifico. Policlinico San Matteo di Pavia; Italia. Università degli Studi di Pavia; Italia Fil: Schlegel, Nicole. Université Paris Diderot - Paris 7; Francia Fil: Klersy, Catherine. Istituti di Ricovero e Cura a Carattere Scientifico. Policlinico San Matteo di Pavia; Italia Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Civaschi, Elisa. Università degli Studi di Pavia; Italia Fil: Pujol Moix, Nuria. Universitat Autònoma de Barcelona; España Fil: Fabris, Fabrizio. Università di Padova; Italia Fil: Favier, Remi. Inserm; Francia. Armand Trousseau Children’s Hospital; Francia. French Reference Center for Inherited Platelet disorders; Francia Fil: Gresele, Paolo. Università di Perugia; Italia Fil: Latger Cannard, Véronique. Centre Hospitalo-Universitaire. Service d’Hématologie Biologique; Francia. Reference French Centre. Centre de Compétence Nord-Est des Pathologies Plaquettaires; Francia Fil: Cuker, Adam. University of Pennsylvania; Estados Unidos Fil: Nurden, Paquita. Hôpital Xavier Arnozan; Francia Fil: Greinacher, Andreas. Institut für Immunologie und Transfusionsmedizin; Alemania Fil: Cattaneo, Marco. Università degli Studi di Milano; Italia Fil: De Candia, Erica. Università Cattolica del Sacro Cuore; Italia Fil: Pecci, Alessandro. Università degli Studi di Pavia; Italia Fil: Hurtaud Roux, Marie Françoise. Université Paris Diderot - Paris 7; Francia Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Muñiz Diaz, Eduardo. Banc de Sang i Teixits de Catalunya. Immunohematology Department; España Fil: Randi, Maria Luigia. Università di Padova; Italia Fil: Trillot, Nathalie. Centre Hospitalier Régional Universitaire de Lille. Pôle Biologie Pathologie Génétique. Institut d’Hématologie-Transfusion; Francia Fil: Bury, Loredana. Università di Perugia; Italia Fil: Lecompte, Thomas. Hôpitaux Universitaires de Genève; Suiza. Université de Genève. Faculté de Médecine; Suiza Fil: Marconi, Caterina. Università di Bologna; Italia Fil: Savoia, Anna. Università degli Studi di Trieste; Italia Fil: Balduini, Carlo L.. Istituti di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; Italia. Università degli Studi di Pavia; Italia Fil: European Hematology Association Scientific Working Group on Thrombocytopenias and Platelet Function Disorders. No especifica

Published
2014

44. Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and alpha-granule deficiency

Author

Roberta Bottega, Ana C. Glembotsky, Anna Savoia, Marco Cattaneo, Patrizia Noris, Alessandro Pecci, Paula G. Heller, Erica De Candia, Daniela De Rocco, Carlo L. Balduini, Nuria Pujol-Moix, Gian Marco Podda, '-', Bottega, Roberta, Alessandro, Pecci, Erica De, Candia, Nuria, Pujol‐moix, Paula G., Heller, Patrizia, Nori, Daniela De, Rocco, Gian Marco, Podda, Ana C., Glembotsky, Marco, Cattaneo, Carlo L., Balduini, Savoia, Anna, Pecci, A., De Candia, E., Pujol Moix, N., Heller, P. G., Noris, P., DE ROCCO, Daniela, Podda, G. M., Glembotsky, A. C., Cattaneo, M, and Balduini, C. L.

Subjects
Proband, Blood Platelets, Sindrome piastrine grigie, CIENCIAS MÉDICAS Y DE LA SALUD, Genotype, RNA Splicing, Haploinsufficiency, Medicina Clínica, Biology, Settore MED/03 - GENETICA MEDICA, NBEAL2, patients, Frameshift mutation, Gray platelet syndrome, Thrombospondin 1, gray platelet syndrome, purl.org/becyt/ford/3.2 [https], medicine, Missense mutation, Humans, Hematología, Allele, Alleles, Genetic Association Studies, Genetics, Hematology, Blood Proteins, Exons, medicine.disease, Phenotype, Thrombocytopenia, Introns, Pedigree, Mutation, purl.org/becyt/ford/3 [https], Original Articles and Brief Reports
Abstract

Background. The gray platelet syndrome (GPS) is a rare inherited bleeding disorder characterized by macrothrombocytopenia and deficiency of alpha-granules in platelets. The genetic defect responsible for GPS was recently identified in biallelic mutations in the NBEAL2 gene. Design and Methods. We studied 11 consecutive families with inherited macrothrombocytopenia of unknown origin and alpha-granule deficiency. All of them underwent NBEAL2 DNA sequencing and evaluation of the platelet phenotype, including a systematic assessment of the alpha-granule content by immunofluorescence analysis for alpha-granule secretory proteins. Results. We identified 9 novel mutations hitting the two alleles of NBEAL2 in 4 probands. They included missense, nonsense and frameshift mutations, as well as nucleotide substitutions that altered the splicing mechanisms as determined at the RNA level. All the individuals with NBEAL2 biallelic mutations showed almost complete absence of platelet -granules. Interestingly, the 13 individuals assumed to be asymptomatic because carriers of a mutated allele had platelet macrocytosis and significant reduction of the -granule content. However, they were not thrombocytopenic. In the remaining 7 probands, we did not identify any NBEAL2 alterations, suggesting that other genetic defect(s) are responsible for their platelet phenotype. Of note, these patients were characterized by a lower severity of the -granule deficiency than individuals with two NBEAL2 mutated alleles. Conclusions. Our data extend the spectrum of mutations responsible for GPS and demonstrate that macrothrombocytopenia with α-granule deficiency is a genetic heterogeneous trait. In terms of practical applications, the screening of NBEAL2 is worthwhile only in patients with macrothrombocytopenia and severe reduction of the α-granules. Finally, individuals carrying one NBEAL2 mutated allele have mild laboratory abnormalities, suggesting that even haploinsufficiency has an effect on platelet phenotype. Fil: Bottega, Roberta. University of Trieste. Department of Medical Science; Italia; Fil: Pecci, Alessandro. University of Pavia and IRCCS Policlinico San Matteo Foundation. Department of Internal Medicine; Italia; Fil: de Candia, Erica. Università Cattolica del Sacro Cuore. Hemostasis and Thrombosis Unit, Policlinico Agostino Gemelli; Italia; Fil: Pujol-Moix, Nuria. Universitat Autònoma de Barcelona. Hospital de la Santa Creu i Sant Pau; España; Fil: Heller, Paula Graciela. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Invest.Medicas; Argentina; Fil: Noris, Patrizia. University of Pavia and IRCCS Policlinico San Matteo Foundation. Department of Internal Medicine; Italia; Fil: de Rocco, Daniela. Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"; Italia; Fil: Podda, Gian Marco. Università degli Studi di Milano. Dipartimento di Scienze della Salute; Italia; Fil: Glembotsky, Ana Claudia. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Invest.Medicas; Argentina; Fil: Cattaneo Marco. Università degli Studi di Milano. Dipartimento di Scienze della Salute; Italia; Fil: Balduini, Carlo L.. University of Pavia and IRCCS Policlinico San Matteo Foundation. Department of Internal Medicine; Italia; Fil: Savoia Anna. Institute for Maternal and Child Health - IRCCS; Italia

Published
2013

45. Management of bleeding and of invasive procedures in patients with platelet disorders and/or thrombocytopenia: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET)

Author

Esther Diana Rossi, Marco Cattaneo, Sergio Siragusa, Carlo L. Balduini, E. De Candia, Alberto Tosetto, G. Mariani, Angelo Claudio Molinari, Tosetto, A, Balduini, CL, Cattaneo, M, De Candia, E, Mariani, G, Molinari, AC, Rossi, E, and Siragusa, S

Subjects
Male, medicine.medical_specialty, Platelet disorder, MEDLINE, Settore MED/15 - Malattie Del Sangue, platelet, transfusion, medicine, Humans, Platelet, Aprotinin, Intensive care medicine, Adverse effect, Desmopressin, business.industry, Settore MED/09 - MEDICINA INTERNA, Hematology, bleeding, medicine.disease, Thrombosis, Thrombocytopenia, Surgery, Bleeding diathesis, Italy, Surgical Procedures, Operative, platelet defects, Female, Blood Platelet Disorders, business, medicine.drug
Abstract

The optimal management of bleeding or its prophylaxis in patients with disorders of platelet count or function is controversial. The bleeding diathesis of these patients is usually mild to moderate: therefore, transfusion of platelet concentrates may be inappropriate, as potential adverse effects might outweigh its benefit. The availability of several anti-hemorrhagic drugs further compounds this problem, mainly because the efficacy/suitability of the various treatment options in different clinical manifestations is not well defined. In these guidelines, promoted by the Italian Society for Studies on Haemostasis and Thrombosis (Società Italiana per lo Studio dell'Emostasi e della Trombosi [SISET]), we aim at offering the best available evidence to help the physicians involved in the management of patients with disorders of platelet count or function. Literature review and appraisal of available evidence are discussed for different clinical settings and for different available treatments, including platelet concentrates (PC), recombinant activated factor VII, desmopressin, antifibrinolytics, aprotinin and local hemostatic agents.

Published
2009

46. Why the disorder induced by GATA1 Arg216Gln mutation should be called 'X-linked thrombocytopenia with thalassemia' rather than 'X-linked gray platelet syndrome'

Author

Carlo L. Balduini, Anna Savoia, Erica De Candia, Balduini, Cl, DE CANDIA, E, and Savoia, Anna

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Mutation, Thalassemia, Platelet, Settore MED/09 - MEDICINA INTERNA, Immunology, GATA1, Cell Biology, Hematology, Biology, medicine.disease_cause, medicine.disease, Thrombocytopenia, Biochemistry, X linked thrombocytopenia, Gray platelet syndrome, gray platelet syndrome, hemic and lymphatic diseases, medicine, OMIM : Online Mendelian Inheritance in Man, Bleeding disorder, Dyserythropoietic anemia
Abstract

To the editor: GATA1 mutations induce 2 X-linked thrombocytopenias: dyserythropoietic anemia with thrombocytopenia (Online Mendelian Inheritance in Man [OMIM] 300367) and X-linked thrombocytopenia with thalassemia (XLTT; OMIM314050). The former has been described in 6 families with 5 different

Published
2007

47. Circulating Activated Platelets in Children With Long Covid: A Case-Controlled Preliminary Observation.

Author

Buonsenso D, Sorrentino S, Ferretti A, Morello R, Valentini P, Di Gennaro L, and De Candia E

Abstract

We investigated if children with Long Covid (n=14) have activated platelets compared with healthy controls (n=14). Platelet activation and secretion markers were investigated by flow cytometry using MoAbs directed against P-selectin, CD63, and PAC-1 in quiescent platelets and in platelets stimulated with 10-µM adenosine diphosphate and 25-µM protease activated receptor 1-activating peptide. Circulating platelets of patients with Long Covid had significantly increased expression of the activation marker cytometry using MoAbs directed against P-selectin (P = 0.019)., Competing Interests: The remaining authors have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Published
2024
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48. Safety and effectiveness of oral anticoagulants in patients with atrial fibrillation and stage 4 chronic kidney disease: a real-world experience.

Author

Talerico R, Brando E, Luzi L, Vedovati MC, Giustozzi M, Verso M, Di Gennaro L, Basso M, Ferretti A, Porfidia A, De Candia E, Pola R, Agnelli G, and Becattini C

Abstract

It is still uncertain whether direct oral anticoagulants (DOACs) perform better than vitamin K antagonists (VKAs) in subjects with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD). The aim of the study was to compare safety and effectiveness of DOACs and VKAs in patients with NVAF and stage 4 CKD (creatinine clearance 15-29 mL/min). We searched the hospital databases of two academic centers to retrospectively identify patients with stage 4 CKD who were on treatment with DOACs or VKAs for NVAF. Safety was the primary outcome of the study and was assessed in terms of incidence of major bleeding (MB). Secondary outcomes were clinically relevant non-major bleeding (CRNMB) and death for any cause. A total of 176 patients (102 on DOACs and 74 on VKAs) were found and included in the analysis. The incidence rate of MB was not statistically different between groups (8.6 per 100 patients-year in the DOAC group and 5.6 per 100 patients-year in the VKA group). Rates of IS/SSE and CRNMB were statistically similar in the two treatment groups, as well. There were less deaths for any cause in the DOAC group than in the VKA group (8.6 and 15.8 per 100 patients-year, respectively), but the difference was not statistically significant. This study found no difference in terms of safety and effectiveness between patients with NVAF and stage 4 CKD treated with DOACs and VKAs. Larger prospective or randomized studies are needed to confirm these findings., (© 2024. The Author(s).)

Published
2024
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49. Platelets and Neurodegenerative Diseases: Current Knowledge and Future Perspectives.

Author

Gallo A, Lipari A, Di Francesco S, Ianuà E, Liperoti R, Cipriani MC, Martone AM, De Candia E, Landi F, and Montalto M

Subjects
Humans, Cognitive Dysfunction metabolism, Animals, Amyloid beta-Peptides metabolism, Platelet Aggregation Inhibitors therapeutic use, Blood Platelets metabolism, Alzheimer Disease metabolism, Platelet Activation, Neurodegenerative Diseases metabolism
Abstract

Platelets have a fundamental role in mediating hemostasis and thrombosis. However, more recently, a new idea is making headway, highlighting the importance of platelets as significant actors in modulating immune and inflammatory responses. In particular, platelets have an important role in the development of vascular amyloid-b-peptide(ab) deposits, known to play a relevant role in Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. The involvement of platelets in the pathogenesis of AD opens up the highly attractive possibility of applying antiplatelet therapy for the treatment and/or prevention of AD, but conclusive results are scarce. Even less is known about the potential role of platelets in mild cognitive impairment (MCI). The aim to this brief review is to summarize current knowledge on this topic and to introduce the new perspectives on the possible role of platelet activation as therapeutic target both in AD and MCI.

Published
2024
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50. MORE EARLY BLEEDS ASSOCIATED WITH HIGH BASELINE DIRECT ORAL ANTICOAGULANT LEVELS IN ATRIAL FIBRILLATION: THE MAS STUDY.

Author

Palareti G, Testa S, Legnani C, Dellanoce C, Cini M, Paoletti O, Ciampa A, Antonucci E, Poli D, Morandini R, Tala M, Chiarugi P, Santoro RC, Iannone AM, De Candia E, Pignatelli P, Faioni EM, Chistolini A, Esteban MDP, Marietta M, Tripodi A, and Tosetto A

Abstract

Treatment with direct oral anticoagulants (DOAC) in atrial fibrillation (AF) patients is effective and safe. However, bleeding complications still occur. Whether the measurement of DOAC levels may further improve treatment efficacy and safety is still an open issue. In the "Measure and See" (MAS) Study (#NCT03803579) venous blood was collected 15-30 days after DOAC initiation in AF patients who were then followed for one year to record the occurrence of major and clinically relevant non-major bleeding. DOAC plasma levels were measured in one laboratory, and results were kept blind to patients and treating doctors. Trough DOAC levels were assessed in 1657 patients [957 (57.7%) and 700 treated with standard and low-dose, respectively]. Fifty bleeding events were recorded during 1606 years of follow-up (3.11% pt/yrs). Fifteen bleeding events (4.97% pt/yrs) occurred in patients with C-trough standardized values in the highest activity class (> 0.50); whereas 35 events (2.69% pt/yrs) occurred in those with values in the two lower classes ( 0.50, p= 0.0401). Increasing DOAC levels and low-dose DOAC use were associated with increased bleeding risk in the first three months of treatment. 19% of patients receiving low doses had standardized activity values in the highest class. More bleeding occurred in patients treated with low (4.3% pt/yrs) than standard (2.2% pt/yrs; p= 0.0160) dose DOAC. Early measurement of DOAC levels in AF patients identified many subjects with high activity levels despite the low doses use and had more bleeding risk during the first 3 months of treatment., (Copyright © 2024 American Society of Hematology.)

Published
2024
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