Article
Hematology
Wenjing Cao, Aria R. Trask, Antonia I. Bignotti, Lindsey A. George, Bhavya S. Doshi, Denise E. Sabatino, Noritaka Yada, Liang Zheng, Rodney M. Camire, X. Long Zheng
Summary: This study aims to determine the effect of FVIII on VWF proteolysis and homeostasis. Through mouse models, recombinant FVIII infusion, and patients with hemophilia A, the study concludes that FVIII plays a pivotal role in regulating VWF proteolysis and homeostasis under various conditions.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Kayleigh M. Voos, Wenpeng Cao, Nicholas A. Arce, Emily R. Legan, Yingchun Wang, Asif Shajahan, Parastoo Azadi, Pete Lollar, Xiaohui Frank Zhang, Renhao Li
Summary: Desialylation of O-glycans around A1 increases its activity by destabilizing the AIM, leading to enhanced binding activity and platelet aggregation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
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
Biology
Klaus Bonazza, Roxana E. Iacob, Nathan E. Hudson, Jing Li, Chafen Lu, John R. Engen, Timothy A. Springer
Summary: This study investigates the regulatory role of N-linker and C-linker in the binding of A1 to GPIb alpha. The results show that the N-linker decreases the affinity of A1 for GPIb alpha, with a stronger contribution from its O-glycan moiety. Additionally, the N-linker regulates the hydrogen deuterium exchange, thermal stability, and urea-induced unfolding of A1. In contrast, the C-linker has no significant effect on the affinity of A1 for GPIb alpha.
Article
Hematology
Matteo Campioni, Paulette Legendre, Cecile Loubiere, Barbara Lunghi, Mirko Pinotti, Olivier D. Christophe, Peter J. Lenting, Cecile V. Denis, Francesco Bernardi, Caterina Casari
Summary: The study explored two independent molecular mechanisms to prevent the detrimental impact of dominant-negative VWF variants in mouse models of dominant VWD, showing beneficial consequences in vivo.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Developmental Biology
J. Pastuschek, C. Baer, C. Goehner, U. Budde, P. Leidenmuehler, T. Groten, E. Schleussner, U. R. Markert
Summary: The research results show that recombinant VWF does not pass through the human placenta, indicating it can be safely used for maternal treatment without causing adverse effects on the fetus.
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
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
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
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
Medicine, General & Internal
Ingrid Skornova, Tomas Simurda, Jan Stasko, Jana Zolkova, Juraj Sokol, Pavol Holly, Miroslava Dobrotova, Ivana Plamenova, Jan Hudecek, Monika Brunclikova, Alena Stryckova, Peter Kubisz
Summary: von Willebrand disease (VWD) is the most common inherited bleeding disorder caused by defects or deficiency of von Willebrand factor. Laboratory testing for VWF-related disorders requires assessment of VWF levels and activity, as well as multimer analysis to evaluate structural features. The introduction of VWF multimer analysis into standard VWD diagnostics helps in patient classification, treatment selection, and dosage determination.
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
Hematology
Seon Jae Choi, Courtney N. Dwyer, Lindsy Rapkin, Matthew Cormier, Charles C. T. Hindmarch, Kate Nesbitt, Alison Michels, Wilma Hopman, Laura L. Swystun, David Lillicrap
Summary: This study investigates the role of von Willebrand factor (VWF) in inflammation-associated venous thrombosis and analyzes the localization and interactions of various thrombus constituents. The results show that inhibiting VWF can reduce venous thrombosis induced by endotoxemia, and most thrombus components are found in the white thrombus regardless of endotoxemia. Furthermore, while endotoxemia modulates the interactions of VWF with other thrombus constituents, the scaffolding network composed of VWF, fibrin, and neutrophil extracellular traps remains largely unaffected.
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)
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
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
Gastroenterology & Hepatology
Eleanor Luce, Clara Steichen, Mickael Allouche, Antonietta Messina, Jean-Marie Heslan, Thierry Lambert, Anne Weber, Tuan Huy Nguyen, Olivier Christophe, Anne Dubart-Kupperschmitt
Summary: Assessing differentiation of induced pluripotent stem cells from hemophilia B patients based on the production and activity of coagulation factor IX reveals the importance of mature hepatocytes for functional recovery in transplantation.
Article
Immunology
Rachel E. Lamerton, Edith Marcial-Juarez, Sian E. Faustini, Marisol Perez-Toledo, Margaret Goodall, Sian E. Jossi, Maddy L. Newby, Iain Chapple, Thomas Dietrich, Tonny Veenith, Adrian M. Shields, Lorraine Harper, Ian R. Henderson, Julie Rayes, David C. Wraith, Steve P. Watson, Max Crispin, Mark T. Drayson, Alex G. Richter, Adam F. Cunningham
Summary: This study investigates the interaction between SARS-CoV-2 antibodies and complement activation using an ELISA assay. The results suggest that the downstream effects of antibody-dependent complement activation may vary depending on the disease status and the specific antigen targeted.
FRONTIERS IN IMMUNOLOGY
(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.
Article
Oncology
Abdullah O. Khan, Antonio Rodriguez-Romera, Jasmeet S. Reyat, Aude-Anais Olijnik, Michela Colombo, Guanlin Wang, Wei Xiong Wen, Nikolaos Sousos, Lauren C. Murphy, Beata Grygielska, Gina Perrella, Christopher B. Mahony, Rebecca E. Ling, Natalina E. Elliott, Christina Simoglou Karali, Andrew P. Stone, Samuel Kemble, Emily A. Cutler, Adele K. Fielding, Adam P. Croft, David Bassett, Gowsihan Poologasundarampillai, Anindita Roy, Sarah Gooding, Julie Rayes, Kellie R. Machlus, Bethan Psaila
Summary: This study presents a human bone marrow organoid that can support the growth and survival of primary cells from patients with myeloid and lymphoid blood cancers. This organoid model allows for mechanistic studies of blood cancers within their microenvironment and serves as an ex vivo tool for prioritizing new therapeutics.
Review
Hematology
Jordan D. D. Dimitrov, Lubka T. T. Roumenina, Gina Perrella, Julie Rayes
Summary: Regardless of the cause, hemolytic diseases are associated with thrombosis, inflammation, and immune dysregulation, resulting in organ damage and poor outcomes. Hemolysis not only leads to anemia and loss of the anti-inflammatory functions of red blood cells, but also releases damage-associated molecular patterns, such as ADP, hemoglobin, and heme, which trigger a hyperinflammatory and hypercoagulable state through various receptors and signaling pathways. Extracellular free heme, in particular, can activate platelets, endothelial cells, innate cells, as well as the coagulation and complement cascades, thereby promoting thrombo-inflammatory events. This review discusses the main mechanisms by which hemolysis, especially heme, drives this thrombo-inflammatory environment and explores the impact of hemolysis on the host response to secondary infections.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
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)