Article
Hematology
Soracha Ward, Jamie M. O'Sullivan, James S. O'Donnell
Summary: Glycosylation is a crucial posttranslational modification that plays a key role in regulating protein biology with variations in glycan structures implicated in human diseases. The heavily glycosylated von Willebrand factor (VWF) with N- and O-linked glycans affecting its structure, function, and half-life, particularly highlighting the significant role of O-linked glycans in modulating VWF biology.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2021)
Article
Biochemistry & Molecular Biology
Marcela Montilla, Isabel Atienza-Navarro, Francisco Jose Garcia-Cozar, Carmen Castro, Francisco Javier Rodriguez-Martorell, Felix A. Ruiz
Summary: Polyphosphate (polyP) plays an important modulatory role in the binding of von Willebrand factor (VWF) and Factor VIII (FVIII) in blood coagulation, and may be used in developing new therapies to activate VWF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Maria Teresa Pagliari, Frits R. Rosendaal, Minoo Ahmadinejad, Zahra Badiee, Mohammad-Reza Baghaipour, Luciano Baronciani, Olga Benitez Hidalgo, Imre Bodo, Ulrich Budde, Giancarlo Castaman, Peyman Eshghi, Jenny Goudemand, Mehran Karimi, Bijan Keikhaei, Riitta Lassila, Frank W. G. Leebeek, Maria Fernanda Lopez Fernandez, Pier Mannuccio Mannucci, Renato Marino, Johannes Oldenburg, Ian Peake, Cristina Santoro, Reinhard Schneppenheim, Andreas Tiede, Gholamreza Toogeh, Alberto Tosetto, Marc Trossaert, Hamideh Yadegari, Eva M. K. Zetterberg, Flora Peyvandi, Augusto B. Federici, Jeroen Eikenboom
Summary: The VWFpp/VWF:Ag ratio indicates missense variants, while the FVIII:C/VWF:Ag ratio does not discriminate between missense and null alleles. The level of VWFpp is not associated with the severity of bleeding symptoms.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Michelle Lavin, Analia Sanchez Luceros, Peter Kouides, Rezan Abdul-Kadir, James S. O'Donnell, Ross Baker, Maha Othman, Sandra L. Haberichter
Summary: The management of pregnant women with von Willebrand disease (VWD) varies internationally, especially in antenatal, peripartum, and postpartum management. There is uncertainty surrounding the use of neuraxial anesthesia (NA) for women with type 2 and type 3 VWD, highlighting the need for international collaborative research efforts to improve care for pregnant women with VWD.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(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
Hematology
Maria Teresa Pagliari, Ulrich Budde, Luciano Baronciani, Peyman Eshghi, Minoo Ahmadinejad, Zahra Badiee, Mohammad-Reza Baghaipour, Olga Benitez Hidalgo, Eugenia Biguzzi, Imre Bodo, Giancarlo Castaman, Jenny Goudemand, Mehran Karimi, Bijan Keikhaei, Riitta Lassila, Frank W. G. Leebeek, Maria Fernanda Lopez Fernandez, Renato Marino, Johannes Oldenburg, Ian Peake, Cristina Santoro, Reinhard Schneppenheim, Andreas Tiede, Gholamreza Toogeh, Alberto Tosetto, Marc Trossaert, Hamideh Yadegari, Eva M. K. Zetterberg, Pier Mannuccio Mannucci, Augusto B. Federici, Jeroen Eikenboom, Flora Peyvandi
Summary: The prevalence of anti-von Willebrand factor (VWF) antibodies was assessed in patients with type 3 von Willebrand disease (VWD). The study found that 8.4% of the subjects tested positive for anti-VWF antibodies, while 6% had neutralizing VWF inhibitors. These inhibitors were mainly found in patients homozygous for VWF null alleles.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Review
Hematology
Omid Seidizadeh, Flora Peyvandi, Pier Mannuccio Mannucci
Summary: Von Willebrand disease is caused by quantitative or qualitative defects of von Willebrand factor (VWF). Type 2N VWD is a rare recessive disorder that requires accurate diagnosis and differentiation from other bleeding disorders such as mild/moderate hemophilia A.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Stephen J. X. Murphy, Soon Tjin Lim, Fionnuala Hickey, Justin A. Kinsella, Deirdre R. Smith, Sean Tierney, Bridget Egan, T. Martin Feeley, Sinead M. Murphy, D. Ronan Collins, Tara Coughlan, Desmond O'Neill, Joseph A. Harbison, Prakash Madhavan, Sean M. O'Neill, Mary-Paula Colgan, James S. O'Donnell, Jamie M. O'Sullivan, George Hamilton, Dominick J. H. McCabe
Summary: The study found that VWF:Ag levels were higher and VWFpp/VWF:Ag ratios were lower in early symptomatic patients with carotid stenosis compared to asymptomatic patients, and these levels decreased over time. Additionally, there was a difference in VWF:Ag levels between patients with blood group O and those without blood group O.
THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Masayuki Kubo, Kazuya Sakai, Masaki Hayakawa, Hirokazu Kashiwagi, Hideo Yagi, Yoshinobu Seki, Atsushi Hasegawa, Haruyuki Tanaka, Itsuto Amano, Yoshiaki Tomiyama, Masanori Matsumoto
Summary: This study investigated whether VWF degradation is enhanced in patients with ET. The results showed that patients with higher platelet counts had lower HMW-VWFM index and higher VWF-DP:VWF Ag ratio. Cytoreductive therapy increased the HMW-VWFM index and decreased the VWF-DP:VWF Ag ratio. In conclusion, an increased platelet count in ET patients is associated with enhanced cleavage of VWF, and cytoreductive therapy can reduce this cleavage and improve VWFM distributions.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Biochemistry & Molecular Biology
Athinoula Meli, Ann McCormack, Ianina Conte, Qu Chen, James Streetley, Marlene L. Rose, Ruben Bierings, Matthew J. Hannah, Justin E. Molloy, Peter B. Rosenthal, Tom Carter
Summary: Cellular and environmental stresses associated with heart disease and heart failure can alter the storage and secretion of VWF, leading to changes in the morphology and function of Weibel-Palade bodies (WPBs) in cardiac microvascular endothelial cells. In patients with dilated cardiomyopathy, WPBs exhibit rounded shape with disordered arrangement of VWF tubules, resulting in impaired VWF deployment during secretion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ellie Gibbs, Amer Khojah, Gabrielle Morgan, Louis Ehwerhemuepha, Lauren M. M. Pachman
Summary: This study aimed to determine if vWF:Ag, a serologic indicator of vascular disease activity, is useful to assess disease activity in children with JDM. The results showed that 25% of untreated JDM patients had elevated vWF:Ag levels, which were associated with disease severity.
Article
Hematology
Eugenia Biguzzi, Simona Maria Siboni, Saskia le Cessie, Luciano Baronciani, Frits R. Rosendaal, Astrid van Hylckama Vlieg, Flora Peyvandi
Summary: The study evaluated the differential increase of VWF and FVIII:C with age among different ages and types of VWD.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Michelle Lavin, Pamela Christopherson, Julie Grabell, Thomas Abshire, Veronica Flood, Sandra L. Haberichter, David Lillicrap, James S. O'Donnell, Robert R. Montgomery, Paula D. James
Summary: This study evaluates the clinical utility of an interim bleeding protocol in VWD patients and provides a new approach to longitudinal bleeding assessment and insights into the evolution of bleeding in VWD.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Connie H. Miller
Summary: In this study, 4 out of 10 VWD3 patients developed VWF inhibitors, with 2 being detected during bleeding episodes and 2 during routine screening. Preanalytical heat treatment was necessary for detecting inhibitors post infusion.
Article
Hematology
Linru Xu, Yanyang Qiu, Yanqing Li, Yaxuan Wei, Yan Wan, Wei Deng
Summary: A new fluorescent protein-VWF chimera (FP-VWF) was developed to monitor the tissue dynamics of VWF distribution, showing similar hematologic function to wild-type VWF. The results indicated the value of FP-VWF in probing the tissue dynamics of VWF in various biological and pharmaceutical applications.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Biochemistry & Molecular Biology
Elena Barbon, Charlotte Kawecki, Solenne Marmier, Aboud Sakkal, Fanny Collaud, Severine Charles, Giuseppe Ronzitti, Caterina Casari, Olivier D. Christophe, Cecile V. Denis, Peter J. Lenting, Federico Mingozzi
Summary: Von Willebrand disease (VWD), the most common inherited bleeding disorder, has limited efficacy with current liver-directed gene therapy. This study developed a gene therapy strategy using an optimized AAV vector and endothelial-targeting peptide to deliver the VWF gene into endothelial cells, achieving long-term expression.
Article
Hematology
Volker Huck, Po-Chia Chen, Emma-Ruoqi Xu, Alexander Tischer, Ulrike Klemm, Camilo Aponte-Santamaria, Christian Mess, Tobias Obser, Fabian Kutzki, Gesa Koenig, Cecile V. Denis, Frauke Graeter, Matthias Wilmanns, Matthew Auton, Stefan W. Schneider, Reinhard Schneppenheim, Janosch Hennig, Maria A. Brehm
Summary: This study uncovered a prothrombotic gain of function associated with a VWF variant located in the C4 domain, leading to an increase in platelet aggregate size and affecting the structural flexibility. The research highlights the uniqueness of this VWF variant and its significance for vascular health.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Cardiac & Cardiovascular Systems
Jeremy Lagrange, Morel E. Worou, Jean-Baptiste Michel, Alexandre Raoul, Melusine Didelot, Vincent Muczynski, Paulette Legendre, Francois Plenat, Guillaume Gauchotte, Marc-Damien Lourenco-Rodrigues, Olivier D. Christophe, Peter J. Lenting, Patrick Lacolley, Cecile Denis, Veronique Regnault
Summary: VWF induces VSMC proliferation through A2 domain binding to LRP4 receptor and integrin alpha(v)beta(3) signaling. These findings provide new insights into the mechanisms that drive physiological repair and pathological hyperplasia of the arterial vessel wall.
CARDIOVASCULAR RESEARCH
(2022)
Article
Hematology
Claire Kizlik-Masson, Ivan Peyron, Stephane Gangnard, Gaelle Le Goff, Solen M. Lenoir, Sandra Damodaran, Marie Clavel, Stephanie Roullet, Veronique Regnault, Antoine Rauch, Flavien Vincent, Emmanuelle Jeanpierre, Annabelle Dupont, Catherine Ternisien, Thibault Donnet, Olivier D. Christophe, Eric van Belle, Cecile Denis, Caterina Casari, Sophie Susen, Peter J. Lenting
Summary: A nanobody (KB-VWF-D3.1) is identified to distinguish proteolyzed and non-proteolyzed VWF and monitor VWF degradation levels. Reduced intact-VWF levels are observed in patients with von Willebrand disease, aortic stenosis, and patients receiving mechanical circulatory support.
Meeting Abstract
Hematology
Vincent Muczynski, Angel Smith, Thibaud Sefiane, Olivier D. Christophe, Peter J. Lenting, David Granger, Kerry Chester, Amit C. Nathwani
Article
Hematology
Stephanie Roullet, Norman Luc, Julie Rayes, Jean Solarz, Dante Disharoon, Andrew Ditto, Emily Gahagan, Christa Pawlowski, Thibaud Sefiane, Frederic Adam, Caterina Casari, Olivier D. Christophe, Michael Bruckman, Peter J. Lenting, Anirban Sen Gupta, Cecile Denis
Summary: The lack of innovation in von Willebrand disease (VWD) is due to the complexity and heterogeneity of the disease and a lack of recognition of the impact of bleeding symptoms experienced by patients. This study proposes a new approach using synthetic platelet (SP) nanoparticles for the treatment of VWD-2B and severe VWD. The results show that SP can improve thrombus formation and reduce blood loss in VWD-2B and VWF-KO mice.
Article
Cardiac & Cardiovascular Systems
Antoine Rauch, Annabelle Dupont, Mickael Rosa, Maximilien Desvages, Christina Le Tanno, Johan Abdoul, Melusine Didelot, Alexandre Ung, Richard Ruez, Emmanuelle Jeanpierre, Melanie Daniel, Delphine Corseaux, Hugues Spillemaeker, Julien Labreuche, Benedicte Pradines, Natacha Rousse, Peter J. Lenting, Mouhamed D. Moussa, Andre Vincentelli, Jean-Claude Bordet, Bart Staels, Flavien Vincent, Cecile V. Denis, Eric Van Belle, Caterina Casari, Sophie Susen
Summary: Thrombocytopenia is consistently observed in ECMO patients, with a time-dependent decrease in platelet count, GP Ib alpha shedding, and increased soluble GP Ib alpha levels. Shedding of GP Ib alpha is dependent on rheological conditions, with higher rates at high-flow speeds.
CIRCULATION RESEARCH
(2023)
Article
Hematology
Alexis Texier, Peter J. Lenting, Cecile Denis, Stephanie Roullet, Olivier D. Christophe
Summary: This study reveals the binding between von Willebrand factor and angiopoietin-2, with angiopoietin-2 enhancing the binding of von Willebrand factor to angiopoietin-1.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Alexandre Kauskot, Coralie Mallebranche, Arnaud Bruneel, Francois Fenaille, Jean Solarz, Toscane Viellard, Miao Feng, Christelle Reperant, Jean-Claude Bordet, Sophie Cholet, Cecile Denis, Genevieve McCluskey, Sylvain Latour, Emmanuel Martin, Isabelle Pellier, Dominique Lasne, Delphine Borgel, Sven Kracker, Alban Ziegler, Marie Tuffigo, Benjamin Fournier, Charline Miot, Frederic Adam
Summary: XMEN disease, caused by loss-of-function mutations in the MAGT1 gene, is associated with platelet dysfunction and defective N-glycosylation, which may explain the bleeding events in patients with XMEN disease.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Melissa Bou-Jaoudeh, Angelina Mimoun, Sandrine Delignat, Ivan Peyron, Ladislas Capdevila, Victoria Daventure, Claire Deligne, Jordan D. Dimitrov, Olivier D. Christophe, Cecile V. Denis, Peter J. Lenting, Valerie Proulle, Sebastien Lacroix-Desmazes
Summary: This study investigated the impact of IdeS treatment in inhibitor-positive HA mice injected with emicizumab. The results showed that IdeS efficiently eliminated anti-FVIII IgG and restored the hemostatic efficacy of exogenous FVIII, unaffected by the presence of emicizumab and polyclonal human IgG in the mice.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Review
Hematology
Robert A. Ariens, Beverley J. Hunt, Ejaife O. Agbani, Josefin Ahnstrom, Robert Ahrends, Raza Alikhan, Alice Assinger, Zsuzsa Bagoly, Alessandra Balduini, Elena Barbon, Christopher D. Barrett, Paul Batty, Jorge David Aivazoglou Carneiro, Wee Shian Chan, Moniek de Maat, Kerstin de Wit, Cecile Denis, Martin H. Ellis, Renee Eslick, Hongxia Fu, Catherine P. M. Hayward, Benoit Ho-Tin-Noe, Frederikus A. Klok, Riten Kumar, Karin Leiderman, Rustem I. Litvinov, Nigel Mackman, Zoe McQuilten, Matthew D. Neal, William A. E. Parker, Roger J. S. Preston, Julie Rayes, Alireza R. Rezaie, Lara N. Roberts, Bianca Rocca, Susan Shapiro, Deborah M. Siegal, Lirlandia P. Sousa, Katsue Suzuki-Inoue, Tahira Zafar, Jiaxi Zhou
Summary: The ISTH London 2022 Congress is the first face-to-face conference since the COVID-19 pandemic. The conference proceedings are also streamed online for those unable to attend. The scientific program covers a wide range of topics and the Illustrated Review article is a revolutionary way to communicate research.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Marie-Daniela Dubois, Ivan Peyron, Olivier-Nicolas Pierre-Louis, Serge Pierre-Louis, Johalene Rabout, Pierre Boisseau, Annika de Jong, Sophie Susen, Jenny Goudemand, Remi Neviere, Pascal Fuseau, Olivier D. Christophe, Peter J. Lenting, Cecile Denis, Caterina Casari
Summary: This study reports two mutations in the D4 domain of VWF that induce combined qualitative and quantitative defects. One mutation leads to almost complete intracellular retention of the protein, while the other mutation results in reduced binding to collagen and platelet receptors.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Lamia Lamrani, Frederic Adam, Christelle Soukaseum, Cecile Denis, Hana Raslova, Jean-Philippe Rosa, Marijke Bryckaert
Summary: This study evaluates the role of filamin A (FLNa) subdomains in regulating integrin alpha IIb beta 3 signaling. The results show that FLNa-actin and FLNa-beta 3 interactions negatively regulate alpha IIb beta 3 activation, while FLNa dimerization domain negatively regulates alpha IIb beta 3 outside-in signaling.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)