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1. Diagnosis and treatment of chronic synovitis in patients with haemophilia: consensus statements from the Italian Association of Haemophilia Centres

Author

Di Minno, Matteo Nicola Dario, Napolitano, Mariasanta, Giuffrida, Anna Chiara, Baldacci, Erminia, Carulli, Christian, Boccalandro, Elena, Bruno, Clarissa, Forneris, Eleonora, Ricca, Irene, Passeri, Walter, Martinelli, Marco, Rivolta, Gianna Franca, Solimeno, Luigi Piero, Martinoli, Carlo, Rocino, Angiola, Pasta, Gianluigi, Aru, Brigida, Balestri, Elena, Biasoli, Chiara, Cantori, Isabella, Coluccia, Antonella, Contino, Laura, Coppola, Antonio, Cultrera, Dorina, Daniele, Filomena, Ettorre, Cosimo Pietro, Giordano, Paola, Iannaccaro, Piergiorgio, Lassandro, Giuseppe, Linari, Silvia, Luciani, Matteo, Malcangi, Giuseppe, Mancuso, Maria Elisa, Marchesini, Emanuela, Marino, Renato, Mazucconi, Maria Gabriella, Molinari, Angelo Claudio, Notarangelo, Lucia Dora, Pasca, Samantha, Quintavalle, Gabriele, Radossi, Paolo, Raso, Simona, Sabatino, Vincenzo, Santagostino, Elena, Santoro, Cristina, Scaturro, Dalila, Zanon, Ezio, Di Minno, Matteo Nicola Dario, Napolitano, Mariasanta, Giuffrida, Anna Chiara, Baldacci, Erminia, Carulli, Christian, Boccalandro, Elena, Bruno, Clarissa, Forneris, Eleonora, Ricca, Irene, Passeri, Walter, Martinelli, Marco, Rivolta, Gianna Franca, Solimeno, Luigi Piero, Martinoli, Carlo, Rocino, Angiola, Pasta, Gianluigi, Aru, Brigida, Balestri, Elena, Biasoli, Chiara, Cantori, Isabella, Coluccia, Antonella, Contino, Laura, Coppola, Antonio, Cultrera, Dorina, Daniele, Filomena, Ettorre, Cosimo Pietro, Giordano, Paola, Iannaccaro, Piergiorgio, Lassandro, Giuseppe, Linari, Silvia, Luciani, Matteo, Malcangi, Giuseppe, Mancuso, Maria Elisa, Marchesini, Emanuela, Marino, Renato, Mazucconi, Maria Gabriella, Molinari, Angelo Claudio, Notarangelo, Lucia Dora, Pasca, Samantha, Quintavalle, Gabriele, Radossi, Paolo, Raso, Simona, Sabatino, Vincenzo, Santagostino, Elena, Santoro, Cristina, Scaturro, Dalila, Zanon, Ezio, and Matteo Nicola Dario Di Minno, Mariasanta Napolitano, Anna Chiara Giuffrida, Erminia Baldacci, Christian Carulli, Elena Boccalandro, Clarissa Bruno, Eleonora Forneris, Irene Ricca, Walter Passeri, Marco Martinelli, Gianna Franca Rivolta, Luigi Piero Solimeno, Carlo Martinoli, Angiola Rocino, Gianluigi Pasta, Dalila Scaturro

Subjects
haemophilia, haemophilic arthropathy, synovitis, Chronic Disease, Consensus, Hemophilia A, Humans, Italy, Synovitis, haemophilia, haemophilic arthropathy, synovitis, Hematology
Abstract

Although synovitis is recognized as a marker of joint disease activity, its periodic assessment is not included in routine clinical surveillance of patients with haemophilia (PwH). In order to evaluate the current knowledge and to identify controversial issues, a preliminary literature search by the Musculoskeletal Committee of the Italian Association of Haemophilia Centres (AICE) has been conducted. Statements have been established and sent to the Italian AICE members to collect their level of agreement or disagreement by a Delphi process. Thirty-seven consensus recommendations have been drafted. We found a general agreement on the indication to consider the presence of synovitis as a marker of joint disease activity in PwH. Accordingly, there was agreement on the indication to search for synovitis both in patients reporting joint pain and in asymptomatic ones, recognizing ultrasound as the most practical imaging technique to perform periodic joint screening. Interestingly, after detection of synovitis, there was agreement on the indication to modify the therapeutic approach, suggesting prophylaxis in patients treated on demand and tailoring treatment in patients already under prophylaxis. Whereas the need of an early consultation with a physiotherapist is recommended for PwH affected by chronic synovitis, the exact timing for an orthopaedic surgeon consultation is currently unknown.

Published
2021
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2. Pain assessment and management in Italian Haemophilia Centres

Author

Di Minno, Matteo N D, Santoro, Cristina, Corcione, Antonio, Di Minno, Giovanni, Martinelli, Marco, Mancuso, Maria E, Acone, Benedetto, Molinari, Angelo C, Passeri, Emilio V, Rocino, Angiola, Santoro, Rita C, Tagliaferri, Annarita, Mattia, Consalvo, Agostini, Paola, Andreoli, Ernesto, Ambaglio, Chiara, Arancio, Fabiola, Aru, Brigida, Baldacci, Erminia, Belfiore, Antonella, Bernasconi, Sayla, Biasoli, Chiara, Borchiellini, Alessandra, Brunetti, Gregorio, Cerbone, Annamaria, Caimi, Teresa, Cantori, Isabella, Coluccia, Antonella, Contino, Laura, Coppetelli, Ugo, Costanzi, Matteo, Cultrera, Dorina, De Cristofaro, Raimondo, Delios, Grazia, Di Gennaro, Leonardo, Di Gregorio, Patrizia, Ettorre, Cosimo Pietro, Fasulo, Rosamaria, Feola, Giulio, Ferretti, Antonietta, Franchini, Massimo, Frizziero, Antonio, Galletti, Lisa, Giuffrida, Gaetano, Giuffrida, Annachiara, Iannaccaro, Piergiorgio, Lassandro, Giuseppe, Linari, Silvia, Lione, Aurora, Lombardo, Rita, Luciani, Matteo, Macchi, Silvia, Maestrini, Giacomo, Malcangi, Giuseppe, Malizia, Raniero, Margaglione, Maurizio, Marietta, Marco, Marino, Renato, Massoud, Michela, Napolitano, Mariasanta, Nichele, Ilaria, Notarangelo, Lucia Dora, Pagano, Cinzia, Pasta, Gianluigi, Pollio, Berardino, Quintavalle, Gabriele, Ranalli, Paola, Raso, Simona, Ricca, Irene, Schiavoni, Mario, Schiavulli, Michele, Sottilotta, Gianluca, Todisco, Angela, Zanon, Ezio, Di Minno, Matteo N D, Santoro, Cristina, Corcione, Antonio, Di Minno, Giovanni, Martinelli, Marco, Mancuso, Maria E, Acone, Benedetto, Molinari, Angelo C, Passeri, Emilio V, Rocino, Angiola, Santoro, Rita C, Tagliaferri, Annarita, Mattia, Consalvo, Agostini, Paola, Andreoli, Ernesto, Ambaglio, Chiara, Arancio, Fabiola, Aru, Brigida, Baldacci, Erminia, Belfiore, Antonella, Bernasconi, Sayla, Biasoli, Chiara, Borchiellini, Alessandra, Brunetti, Gregorio, Cerbone, Annamaria, Caimi, Teresa, Cantori, Isabella, Coluccia, Antonella, Contino, Laura, Coppetelli, Ugo, Costanzi, Matteo, Cultrera, Dorina, De Cristofaro, Raimondo, Delios, Grazia, Di Gennaro, Leonardo, Di Gregorio, Patrizia, Ettorre, Cosimo Pietro, Fasulo, Rosamaria, Feola, Giulio, Ferretti, Antonietta, Franchini, Massimo, Frizziero, Antonio, Galletti, Lisa, Giuffrida, Gaetano, Giuffrida, Annachiara, Iannaccaro, Piergiorgio, Lassandro, Giuseppe, Linari, Silvia, Lione, Aurora, Lombardo, Rita, Luciani, Matteo, Macchi, Silvia, Maestrini, Giacomo, Malcangi, Giuseppe, Malizia, Raniero, Margaglione, Maurizio, Marietta, Marco, Marino, Renato, Massoud, Michela, Napolitano, Mariasanta, Nichele, Ilaria, Notarangelo, Lucia Dora, Pagano, Cinzia, Pasta, Gianluigi, Pollio, Berardino, Quintavalle, Gabriele, Ranalli, Paola, Raso, Simona, Ricca, Irene, Schiavoni, Mario, Schiavulli, Michele, Sottilotta, Gianluca, Todisco, Angela, and Zanon, Ezio

Subjects
Factor IX, Italy, Humans, Pain Management, pain heamophilia, Hemophilia A, blood coagulation disorders, haemophilia, pain perception, pain management, surveys, Haemostasis and Thrombosis, Pain Measurement
Abstract

BACKGROUND: Although the widespread use of factor VIII/IX replacement therapy has significantly reduced the severity of arthropathy in persons with haemophilia (PWH), some develop degenerative joint changes, associated with significant pain. The aim of this survey was to investigate the management and perception of pain among Italian physicians who treat PWH. MATERIALS AND METHODS: Between September and October 2017, a questionnaire was distributed to 35 Italian haemophilia treatment centres (60 physicians). RESULTS: Fifty-three haemophilia specialists completed the survey. We found that there was good agreement (98.1%) on the need to investigate pain at each clinical visit, but there was heterogeneity in the opinions of haemophilia specialists with regards to the availability of validated guidelines (35.8%) and whether pain specialists should be a part of the comprehensive care team in daily clinical practice (58.5%). Haemophilia specialists also agreed pain should be evaluated using a rating scale validated in PWH (88.7%). Pain was mainly managed by the haemophilia specialists themselves, supported by a physiatrist and physiotherapist, while a pain specialist was only involved in 26.4% of cases. The combination of paracetamol with tramadol or codeine was the most common first-line treatment, while cyclo-oxygenase-2 inhibitors, non-steroidal anti-inflammatory drugs, and opioids were less commonly used. DISCUSSION: There are some unmet needs in Italy regarding pain management for PWH and the management of pain in these patients by haemophilia specialists. There is a lack of evidence-based guidelines for these specialists to use, as well as a reluctance to involve pain specialists. The lack of spontaneous reporting of pain by PWH, despite using pain relief, highlights the need for clinicians to actively ask patients about any pain they may be experiencing.

Published
2021

3. Acquired inhibitors of clotting factors: AICE recommendations for diagnosis and management

Author

Franchini, Massimo, Castaman, Giancarlo, Coppola, Antonio, Santoro, Cristina, Zanon, Ezio, Di Minno, Giovanni, Morfini, Massimo, Santagostino, Elena, Rocino, Angiola, Abbate, Rosanna, Aru, Anna Brigida, Biasoli, Chiara, Borchiellini, Alessandra, Caimi, Teresa Maria, Cantori, Isabella, Cerbone, Anna Maria, Cesaro, Simone, Ciabatta, Carlo, Coluccia, Antonella, Contino, Laura, Cultrera, Dorina, De Cristofaro, Raimondo, Delios, Grazia, Di Minno, Matteo Nicola Dario, Dragani, Alfredo, Ettorre, Cosimo Pietro, Feola, Giulio, Gamba, Gabriella, Gandini, Giorgio, Giuffrida, Anna Chiara, Giuffrida, Gaetano, Gresele, Paolo, Hassan, Hamisa Jane, Lassandro, Giuseppe, Latella, Caterina, Linari, Silvia, Luciani, Matteo, Mancuso, Maria Elisa, Marchesini, Emanuela, Marino, Renato, Matino, Davide, Mazzucconi, Maria Gabriella, Messina, Maria, Milan, Marta, Molinari, Angelo Claudio, Napolitano, Mariasanta, Notarangelo, Lucia Dora, Peyvandi, Flora, Pollio, Berardino, Radossi, Paolo, Riccardi, Federica, Riva, Silvia, Rivolta, Gianna Franca, Rossetti, Gina, Santoro, Rita Carlotta, Serino, Maria Luisa, Schiavulli, Michele, Schiavoni, Mario, Schinco, Piercarla, Solimeno, Luigi Piero, Sottilotta, Gianluca, Targhetta, Roberto, Tagliaferri, Annarita, Testa, Sophie, Todisco, Angela, Turello, Marina, Valdrè, Lelia, Franchini M., Castaman G., Coppola A., Santoro C., Zanon E., Di Minno G., Morfini M., Santagostino E., Rocino A., Abbate R., Aru A.B., Biasoli C., Borchiellini A., Caimi T.M., Cantori I., Cerbone A.M., Cesaro S., Ciabatta C., Coluccia A., Contino L., Cultrera D., De Cristofaro R., Delios G., Di Minno M.N.D., Dragani A., Ettorre C.P., Feola G., Gamba G., Gandini G., Giuffrida A.C., Giuffrida G., Gresele P., Hassan H.J., Lassandro G., Latella C., Linari S., Luciani M., Mancuso M.E., Marchesini E., Marino R., Matino D., Mazzucconi M.G., Messina M., Milan M., Molinari A.C., Napolitano M., Notarangelo L.D., Peyvandi F., Pollio B., Radossi P., Riccardi F., Riva S., Rivolta G.F., Rossetti G., Santoro R.C., Serino M.L., Schiavulli M., Schiavoni M., Schinco P., Solimeno L.P., Sottilotta G., Targhetta R., Tagliaferri A., Testa S., Todisco A., Turello M., Valdre L., Franchini, Massimo, Castaman, Giancarlo, Coppola, Antonio, Santoro, Cristina, Zanon, Ezio, DI MINNO, Giovanni, Morfini, Massimo, Santagostino, Elena, Rocino, Angiola, Group Author: Abbate, Rosanna, Aru, Anna Brigida, Biasoli, Chiara, Borchiellini, Alessandra, Caimi, Teresa Maria, Cantori, Isabella, Cerbone, Anna Maria, Cesaro, Simone, Ciabatta, Carlo, Coluccia, Antonella, Contino, Laura, Cultrera, Dorina, De Cristofaro, Raimondo, Delios, Grazia, DI MINNO, matteo nicola dario, Dragani, Alfredo, Ettorre, Cosimo Pietro, Feola, Giulio, Gamba, Gabriella, Gandini, Giorgio, Giuffrida, Anna Chiara, Giuffrida, Gaetano, Gresele, Paolo, Hassan, Hamisa Jane, Lassandro, Giuseppe, Latella, Caterina, Linari, Silvia, Luciani, Matteo, Mancuso, Maria Elisa, Marchesini, Emanuela, Marino, Renato, Matino, Davide, Mazzucconi, Maria Gabriella, Messina, Maria, Milan, Marta, Molinari, Angelo Claudio, Napolitano, Mariasanta, Notarangelo, Lucia Dora, Peyvandi, Flora, Pollio, Berardino, Radossi, Paolo, Riccardi, Federica, Riva, Silvia, Rivolta, Gianna Franca, Rossetti, Gina, Santoro, Rita Carlotta, Serino, Maria Luisa, Schiavulli, Michele, Schiavoni, Mario, Schinco, Piercarla, Solimeno, Luigi Piero, Sottilotta, Gianluca, Targhetta, Roberto, Tagliaferri, Annarita, Testa, Sophie, Todisco, Angela, Turello, Marina, and Valdrè, Lelia

Subjects
Male, Autoantibodies, Blood Coagulation Factor Inhibitors, Female, Humans, Hemophilia A, Immunology and Allergy, Hematology, Blood Coagulation Factor Inhibitor, Recommendation, Autoantibodie, Human
Published
2015

6. Assessment of the olfactory function in Italian patients with type 3 von Willebrand disease caused by a homozygous 253 Kb deletion involving VWF and TMEM16B/ANO2

Author

Paolo Gasparini, Anna Morgan, Renato Marino, Valentina Cenedese, Maurizio Margaglione, Cosimo Ettorre, Massimo Mezzavilla, Anna Maria Menini, Cenedese, Valentina, Mezzavilla, Massimo, Morgan, Anna, Marino, Renato, Ettorre, Cosimo Pietro, Margaglione, Maurizio, Gasparini, Paolo, and Menini, ANNA MARIA

Subjects
Olfactory system, Male, smell identification test, vonwillebrand-factor, lcsh:Medicine, population, amplification, Settore BIO/09 - Fisiologia, type 3 von Willebrand disease, activated chloride channel, deletion, lcsh:Science, Sequence Deletion, Genetics, education.field_of_study, Multidisciplinary, biology, Homozygote, Middle Aged, transduction, Smell, medicine.anatomical_structure, sensory neurons, protein, tmem16a, cilia, Italy, VWF and TMEM16B/ANO2, Female, Research Article, Adult, Population, Anoctamins, von Willebrand Disease, Type 3, Olfactory mucosa, Young Adult, Von Willebrand factor, Olfactory Mucosa, von Willebrand Factor, medicine, Von Willebrand disease, Humans, education, Chromosome 12, Genetic Association Studies, lcsh:R, Wild type, Membrane Proteins, medicine.disease, Olfactory Perception, Case-Control Studies, biology.protein, lcsh:Q, Olfactory epithelium
Abstract

Type 3 Von Willebrand disease is an autosomal recessive disease caused by the virtual absence of the von Willebrand factor (VWF). A rare 253 kb gene deletion on chromosome 12, identified only in Italian and German families, involves both the VWF gene and the N-terminus of the neighbouring TMEM16B/ANO2 gene, a member of the family named transmembrane 16 (TMEM16) or anoctamin (ANO). TMEM16B is a calcium-activated chloride channel expressed in the olfactory epithelium. As a patient homozygous for the 253 kb deletion has been reported to have an olfactory impairment possibly related to the partial deletion of TMEM16B, we assessed the olfactory function in other patients using the University of Pennsylvania Smell Identification Test (UPSIT). The average UPSIT score of 4 homozygous patients was significantly lower than that of 5 healthy subjects with similar sex, age and education. However, 4 other members of the same family, 3 heterozygous for the deletion and 1 wild type, had a slightly reduced olfactory function indicating that socio-cultural or other factors were likely to be responsible for the observed difference. These results show that the ability to identify odorants of the homozygous patients for the deletion was not significantly different from that of the other members of the family, showing that the 253 kb deletion does not affect the olfactory performance. As other genes may compensate for the lack of TMEM16B, we identified some predicted functional partners from in silico studies of the protein-protein network of TMEM16B. Calculation of diversity for the corresponding genes for individuals of the 1000 Genomes Project showed that TMEM16B has the highest level of diversity among all genes of the network, indicating that TMEM16B may not be under purifying selection and suggesting that other genes in the network could compensate for its function for olfactory ability.

Published
2015

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