Article
Multidisciplinary Sciences
Katarina D. Kovacevic, Stefan Greisenegger, Agnes Langer, Georg Gelbenegger, Nina Buchtele, Ingrid Pabinger, Karin Petroczi, Shuhao Zhu, James C. Gilbert, Bernd Jilma
Summary: BT200, a third generation anti-VWF aptamer, showed potential for secondary stroke prevention in patients with large artery atherosclerosis stroke by reducing VWF activity, VWF-dependent platelet function and prolonging closure times. Its target concentration-dependent manner and favorable safety profile in phase I trials make it an interesting drug candidate.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Caterina Casari, Remi Favier, Paulette Legendre, Alexandre Kauskot, Frederic Adam, Veronique Picard, Peter J. Lenting, Cecile Denis, Valerie Proulle
Summary: This report describes the successful treatment of splenic injury in a patient with p.V1316M-associated VWD2B and chronic thrombocytopenia using nonoperative management and a combination of VWF replacement therapy and platelet transfusions relayed by TPO-RA.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2022)
Article
Hematology
Nikolett Wohner, Silvie Sebastian, Vincent Muczynski, Dana Huskens, Bas de Laat, Philip G. de Groot, Peter J. Lenting
Summary: The study reveals that VWF strings secreted from endothelial cells are only partially covered with platelets, and osteoprotegerin plays a role in regulating platelet adhesion to VWF. This regulatory mechanism may be more relevant under inflammatory conditions.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Engineering, Biomedical
Noel G. Tsyu, Aleksey V. Belyaev
Summary: A multi-subunit glycoprotein called Von Willebrand factor (VWF) in blood plasma is responsible for mediating platelet adhesion to damaged blood vessel walls. The adhesion of VWF to collagen is crucial for platelet hemostasis and thrombosis, acting as a molecular bridge between injury and platelet adhesion receptors. This study proposes a simulation framework for VWF-mediated platelet adhesion under the influence of shear flow, using particles representing VWF multimers and platelets immersed in a viscous fluid. The model considers the flattened platelet shape and balances detail of description with computational complexity.
INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING
(2023)
Article
Hematology
Maurice Swinkels, Sophie Hordijk, Petra E. Buergisser, Johan A. Slotman, Tom Carter, Frank W. G. Leebeek, A. J. Gerard Jansen, Jan Voorberg, Ruben Bierings
Summary: This study investigated the release of VWF and VWFpp from individual alpha-granules in response to different physiological stimuli. The results showed that the secretion of alpha-granule cargo increased in a dose-dependent manner upon activation of PAR-1 and GPVI signaling pathways. However, there were differential release patterns for VWF and VWFpp.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemistry & Molecular Biology
Sergey Okhota, Sergey Kozlov, Yuliya Avtaeva, Ivan Melnikov, Olga Saburova, Konstantin Guria, Evgeny Matroze, Zufar Gabbasov
Summary: This study examined platelet adhesion mediated by von Willebrand factor (VWF) at high shear rates in patients with premature coronary artery disease (CAD). The researchers found that patients with premature CAD exhibited a greater GPIb-mediated component of platelet adhesion compared to control patients. This suggests a potential role of excessive VWF-platelet interactions in the development of premature CAD.
Article
Hematology
Catarina Monteiro, Ana Goncalves, Monica Pereira, Catarina Lau, Sara Morais, Rosario Santos
Summary: Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant bleeding disorder characterized by increased platelet aggregation and enhanced affinity of GPIba to VWF. A novel heterozygous variant of GP1BA, likely causing the PT-VWD phenotype, was identified in the patient through genetic sequencing.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Cell Biology
Thorsten Kragh, Isabell Pekrul, Helmut W. Ott, Michael Spannagl, Patrick Moehnle
Summary: The interaction of platelets with von Willebrand factor is crucial for primary hemostasis. The study proposes a method for laboratory assessment and reporting of platelet von Willebrand factor, providing estimates of activity and concentration of platelet von Willebrand factor in healthy individuals.
Article
Hematology
Predrag Miljic, Abdelrahman Noureldin, Michelle Lavin, Sajida Kazi, Analia Sanchez-Luceros, Paula D. James, Maha Othman
Summary: This study examined the diagnostic and management approaches and outcomes in women with type 2B von Willebrand disease during pregnancy. The findings highlight the challenges and uncertainties in managing these patients, such as bleeding complications, unknown target safe VWF level, diverse hemostatic management practices, and varied views on delivery mode and anesthesia use.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemistry & Molecular Biology
Johana Hrdinova, Delia I. Fernandez, Bogac Ercig, Bibian M. E. Tullemans, Dennis P. L. Suylen, Stijn M. Agten, Kerstin Jurk, Tilman M. Hackeng, Karen Vanhoorelbeke, Jan Voorberg, Chris P. M. Reutelingsperger, Kanin Wichapong, Johan W. M. Heemskerk, Gerry A. F. Nicolaes
Summary: This study designed and synthesized stable cyclic peptides to interfere with the interaction between VWF A1 domain and GPIb alpha. The selected peptides showed low binding free energy and retained their interference in the binding of VWF to GPIb-V-IX, as confirmed by flow cytometry. These peptides phenotypically mimicked the changes seen with the anti-VWF A1 domain antibody CLB-RAg35, although they were less potent. The improved peptide opt-mono-ORbIT demonstrated increased inhibitory activity under flow.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Paola Colpani, Luciano Baronciani, Francesca Stufano, Giovanna Cozzi, Marco Boscarino, Maria Teresa Pagliari, Eugenia Biguzzi, Flora Peyvandi
Summary: This study evaluated four different assays to diagnose and detect various von Willebrand disease (VWD) variants. The VWF:GPIbM-automated assay was the most effective in diagnosing type 2B, while the VWF:RCo assays were the most effective in detecting type 2M and 2M/2A variants. The VWF:GPIbM ELISA overestimated the activity of type 2B patients lacking high-molecular-weight multimers (HMWM). Using a VWF activity/VWF:antigen ratio cut-off of 0.70 reduced the number of misdiagnosed patients by half.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Chemistry, Multidisciplinary
Valentina Drago, Luisa Di Paola, Claire Lesieur, Renato Bernardini, Claudio Bucolo, Chiara Bianca Maria Platania
Summary: In this study, a computational approach was used to analyze the binding of FVIII with VWF, revealing that the A3-C1 domains of B domain-deleted FVIII are the preferential binding site for VWF. This computational method can be applied to the rational design of other biologic drugs.
APPLIED SCIENCES-BASEL
(2022)
Article
Hematology
Justine H. Ryu, Kenneth A. Bauer, Sol Schulman
Summary: This report describes the successful perioperative management of a patient with type 2N VWD using the recombinant FVIII product efanesoctocog alfa. By decoupling the FVIII-VWF interaction, efanesoctocog alfa achieves prolonged FVIII circulation and mitigates potential cardiovascular risks.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Critical Care Medicine
Xue D. Manz, Robert Szulcek, Xiaoke Pan, Petr Symersky, Chris Dickhoff, Jisca Majolee, Veerle Kremer, Elisabetta Michielon, Ekaterina S. Jordanova, Teodora Radonic, Irene Bijnsdorp, Sander R. Piersma, Thang Pham, Connie R. Jimenez, Anton Vonk Noordegraaf, Frances S. de Man, Reinier A. Boon, Jan Voorberg, Peter L. Hordijk, Jurjan Aman, Harm Jan Bogaard
Summary: This study identifies the role of von Willebrand factor (vWF) in chronic thromboembolic pulmonary hypertension (CTEPH). Increased vWF levels in plasma and pulmonary endothelium of CTEPH patients contribute to elevated platelet adhesion to CTEPH endothelium. The increased expression of nuclear factor (NF)-kappa B2 and epigenetic modifications of the vWF promoter play a critical role in driving vWF transcription and promoting a prothrombotic phenotype in CTEPH-pulmonary artery endothelial cells.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Hematology
Noriko Tamura, Kazuya Shimizu, Seiji Shiozaki, Kazuyasu Sugiyama, Masamitsu Nakayama, Shinichi Goto, Shu Takagi, Shinya Goto
Summary: The role of erythrocytes in platelet adhesion to von Willebrand factor (VWF) on the vessel wall has been investigated through both biological experiments and computer simulations. The results show that the presence of erythrocytes positively correlates with the rate of platelet adhesion, regardless of whether the erythrocytes are native, fixed, or artificial. This suggests that erythrocytes play an important role in facilitating platelet adhesion to VWF.
THROMBOSIS AND HAEMOSTASIS
(2022)
Letter
Medicine, General & Internal
Mariangela Scavone, Gian Marco Podda, Elena Bossi, Rita Paroni, Marco Cattaneo
WIENER KLINISCHE WOCHENSCHRIFT
(2022)
Letter
Hematology
Sabina Chiaretti, Massimiliano Bonifacio, Roberta Agrippino, Fabio Giglio, Mario Annunziata, Antonio Curti, Maria Ilaria Del Principe, Prassede Salutari, Mariarita Sciume, Mario Delia, Marco Armenio, Valentina Mancini, Antonino Mule, Francesco Grimaldi, Giovanna Rege-Cambrin, Lidia Santoro, Federico Lussana, Patrizia Chiusolo, Crescenza Pasciolla, Anna Maria Scattolin, Marco Cerrano, Maria Ciccone, Marzia Defina, Fabio Forghieri, Carla Mazzone, Matteo Piccini, Felicetto Ferrara, Giovanni Pizzolo, Robin Foa
Summary: The management of patients with hematologic malignancies, particularly acute lymphoblastic leukemia (ALL), during the COVID-19 pandemic is challenging. This cross-sectional observational study conducted in Italian hematology centers explored the characteristics and management of COVID-19-infected ALL patients.
Article
Clinical Neurology
Emanuele Cerulli Irelli, Enrico Cocchi, Georgia Ramantani, Antonella Riva, Roberto Horacio Caraballo, Alessandra Morano, Loretta Giuliano, Tulay Yilmaz, Eleni Panagiotakaki, Francesca F. Operto, Beatriz Gonzalez Giraldez, Simona Balestrini, Katri Silvennoinen, Sara Casciato, Marion Comajuan, Francesco Fortunato, Anna Teresa Giallonardo, Rimma Gamirova, Antonietta Coppola, Giancarlo Di Gennaro, Angelo Labate, Vito Sofia, Gerhard Josef Kluger, Antonio Gambardella, Dorothee G. A. Kasteleijn-NolstTrenite, Betul Baykan, Sanjay M. Sisodiya, Alexis Arzimanoglou, Pasquale Striano, Carlo Di Bonaventura
Summary: Based on age at epilepsy onset (AEO), this study identified three subtypes of objective epilepsy with eyelid myoclonia (EEM) and analyzed their distinct clinical features. Early onset EEM was associated with higher rates of intellectual disability, antiseizure medication refractoriness, and psychiatric comorbidities, while late onset EEM had the highest proportion of myoclonia involving body regions other than eyelids and generalized tonic-clonic seizures. Intermediate onset EEM had the lowest observed rate of additional findings. Family history of EEM was more frequent in the subtypes with intermediate and late onset. Patients with body-MYO showed higher rates of migraine and generalized tonic-clonic seizures.
Article
Psychiatry
Katherine Turner, Anna Castelnovo, Lampros Perogamvros, Robert C. Cloninger, Andrea Galbiati, Alessia Bertolotti, Paola Proserpio, Michele Terzaghi, Raffaele Manni, Luigi Ferini Strambi, Lino Nobili, Mauro Manconi, Maria Paola Canevini, Elena Zambrelli
Summary: This study aimed to compare the personality traits of children and adolescents with and without disorders of arousal (DOA). The results showed that patients with DOA had higher scores on assessment measures such as PADSS and SDSC, as well as higher scores on novelty seeking, harm avoidance, and self-transcendence subscales in the JTCI. They also had lower scores on the self-directedness subscale.
JOURNAL OF PSYCHIATRIC RESEARCH
(2023)
Letter
Cell Biology
Mariangela Scavone, Gian Marco Podda, Armando Tripodi, Marco Cattaneo
Review
Oncology
Federico Lussana, Gianluca Cavallaro, Pantaleo De Simone, Alessandro Rambaldi
Summary: In this review, the impact of novel immune therapies on the treatment of acute lymphoblastic leukemia (ALL) in children and adults was discussed. Results from trials evaluating the incorporation of these new drugs into frontline treatments show promising clinical benefit. Clinical conditions, such as high tumor burden or extra medullary relapse, still have poor clinical outcome despite the promising results. Combination of immunotherapies with chemotherapy in frontline treatment is being evaluated to increase the rate and depth of molecular remission. The use of tyrosine kinase inhibitors and immunotherapy in Ph-positive ALL has shown unprecedented rates of remission and long-term cure. The development of potentially curative treatment modalities for older ALL patients who cannot receive intensive chemotherapy is also highlighted.
Article
Health Care Sciences & Services
Katherine Turner, Francesca La Briola, Aglaia Vignoli, Elena Zambrelli, Valentina Chiesa, Laura Fongoni, Olivia Baldi, Maria Paola Canevini
Summary: The study aims to characterize the behavioral profiles of adolescents with epilepsy, assess psychopathological disorders, and investigate the relationships between epilepsy, psychological functioning, and clinical variables. The findings reveal that 55.2% of adolescents with epilepsy have emotional disturbances, including body dissatisfaction, anxiety, interpersonal conflicts, family problems, uncertainty about the future, and self-esteem/well-being disorders. Gender and poor seizure control are associated with specific emotional features. Therefore, it is important to screen for emotional distress, recognize impairments, and provide appropriate treatment and follow-up for adolescents with epilepsy.
Review
Cardiac & Cardiovascular Systems
Bianca Clerici, Marco Cattaneo
Summary: Aspirin irreversibly inhibits platelet function by inhibiting the synthesis of TxA2. Although widely used at low doses for cardiovascular prevention, chronic treatment with aspirin can lead to gastrointestinal discomfort, mucosal erosions/ulcerations, and bleeding. Enteric-coated (EC) aspirin, the most commonly used formulation, is less effective than plain aspirin in inhibiting TxA2 production, especially in individuals with high body weight. It causes fewer erosions in the stomach but can still cause mucosal erosions in the small intestine. Several studies have shown that EC aspirin and buffered aspirin do not significantly reduce the incidence of clinically relevant gastrointestinal ulceration and bleeding. Plain aspirin should be the preferred formulation for cardiovascular prevention due to its favorable pharmacological profile.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2023)
Article
Hematology
Marta Brambilla, Alessia Becchetti, Gian Enrico Rovati, Nicola Cosentino, Maria Conti, Paola Canzano, Peter L. A. Giesen, Alessia Loffreda, Alice Bonomi, Marco Cattaneo, Erica De Candia, Gian Marco Podda, Daniela Trabattoni, Pablo Jose Werba, Jeness Campodonico, Christian Pinna, Giancarlo Marenzi, Elena Tremoli, Marina Camera
Summary: ADP-induced platelet activation leads to the expression of tissue factor (TF) on the cell surface. The study demonstrates that P2Y(12) receptors play a role in regulating TF expression, and P2Y(12) antagonists can reduce the percentage of TF-positive platelets. Assessment of TF-positive platelets can be used to identify patients with residual platelet reactivity.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Behavioral Sciences
G. Ferrera, E. Ricci, A. Vignoli, M. N. Savini, I. Vigano, V. Chiesa, D. Caputo, E. Zambrelli, F. La Briola, K. Turner, M. P. Canevini
Summary: This retrospective study aimed to evaluate the effects of highly purified, pharmaceutical-grade CBD on seizure frequency, quality of life (QoL), behavior, parental stress, and sleep in patients with drug-resistant epilepsy (DRE). The results showed that CBD decreased seizure frequency in 50% of the patients, with no serious adverse effects. CBD did not significantly affect sleep or parental stress, but it improved social interaction in QoL. These findings suggest that CBD is a safe and effective anti-seizure medication with potential benefits in other childhood disabilities.
EPILEPSY & BEHAVIOR
(2023)
Meeting Abstract
Clinical Neurology
M. P. Canevini, O. Mecarelli, G. Di Gennaro, A. D'Aniello, A. T. Giallonardo, U. Aguglia, G. Assenza, A. Gambardella, G. Coppola, P. Veggiotti, V. De Giorgis, C. Cerminara, F. Vigevano, S. Goldman, A. Patten, P. Mansi, A. Milan, A. Gentile
Meeting Abstract
Clinical Neurology
A. Gambardella, G. Di Gennaro, A. D'Aniello, A. T. Giallonardo, O. Mecarelli, U. Aguglia, G. Assenza, M. P. Canevini, G. Coppola, P. Veggiotti, V. De Giorgis, C. Cerminara, F. Vigevano, S. Goldman, A. Patten, P. Mansi, A. Milan, A. Gentile
Meeting Abstract
Clinical Neurology
L. Turacchi, A. Lividini, V. Rovelli, K. Turner, E. Salvatici, G. Banderali, M. P. Canevini, E. Zambrelli
Article
Genetics & Heredity
Angela Peron, Maria Paola Canevini, Filippo Ghelma, Rosangela Arancio, Miriam Nella Savini, Aglaia Vignoli
Summary: Clinical manifestations and management of adult patients with Rett syndrome were assessed in this study. The results showed that adult patients with Rett syndrome still experience a range of symptoms and issues, such as epilepsy, sleep problems, and behavioral disorders. A transitional program and a multidisciplinary team are needed to optimize the clinical management of these patients.
JOURNAL OF MEDICAL GENETICS
(2022)
