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
Liang Zheng, Liyun Cao, X. Long Zheng
Summary: This study reveals the protective role of ADAMTS13 or lack of VWF in reducing irradiation and melanoma-induced thrombotic microangiopathy and mortality. The microenvironment created by plasma ADAMTS13 or lack of VWF may affect melanoma cell phenotypes through alteration of oxidation-reduction and lipid metabolic pathways.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Review
Hematology
Dafna J. Groeneveld, Lauren G. Poole, James P. Luyendyk
Summary: Liver disease is associated with significant changes in the hemostatic system, with anticoagulants showing promise in slowing disease progression but also posing bleeding risks. Elevated levels of VWF may accelerate intrahepatic thrombosis, suggesting a potential link between VWF function and the progression of liver disease.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
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)
Review
Medicine, General & Internal
Parnian Alavi, Abhisha M. Rathod, Nadia Jahroudi
Summary: Endothelial cells have the capacity to express both pro and anticoagulant molecules, but they mainly function to maintain a non-thrombogenic surface under normal conditions. When stimulated, injured, or dysfunctional, endothelial cells release VWF, a procoagulant protein that plays a central role in platelet aggregation and thrombus formation. With aging, there is a significant increase in VWF levels, which correlates with a rise in thrombotic events, but the reasons for this age-related increase remain unclear.
JOURNAL OF CLINICAL MEDICINE
(2021)
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
Medicine, General & Internal
Jun Kit He, Samuel Schick, Marshall Williams, Bradley Wills, Martim Pinto, Gean Viner, Eugene Brabston, Amit Momaya, X. Long Zheng, Brent Ponce
Summary: This study found that following TSA surgery, patients had decreased ADAMTS13 activity, increased VWF levels, and the lowest ADAMTS13/VWF ratio, suggesting that the highest risk for VTE may be on postoperative day 2. Proper anticoagulation treatment is recommended during this period.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Health Care Sciences & Services
Chanukya K. Colonne, Emmanuel J. Favaloro, Leonardo Pasalic
Summary: von Willebrand factor (VWF) and ADAMTS13 play important roles in normal hemostasis and can be involved in abnormal hemostasis in malignancy. VWF may also contribute to inflammation, angiogenesis, tumor biology, and tumor metastasis. VWF and ADAMTS13 have been explored as tumor biomarkers, but their clinical utility is currently limited. Further studies are needed to understand the relationships between VWF, ADAMTS13, and malignancy.
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
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
Hematology
Miruna Popa, Markus Hecker, Andreas H. Wagner
Summary: ADAMTS13 is a metalloprotease whose expression is inhibited by proinflammatory cytokines, potentially increasing the risk of arterial thrombosis. Factors associated with atherosclerosis do not seem to affect ADAMTS13 expression. There is a reciprocal correlation between the expression of ADAMTS13 and vWF in endothelial cells.
THROMBOSIS AND HAEMOSTASIS
(2022)
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
Ilaria Mancini, Luciano Baronciani, Andrea Artoni, Paola Colpani, Marina Biganzoli, Giovanna Cozzi, Cristina Novembrino, Massimo Boscolo Anzoletti, Valentina De Zan, Maria Teresa Pagliari, Roberta Gualtierotti, Stefano Aliberti, Mauro Panigada, Giacomo Grasselli, Francesco Blasi, Flora Peyvandi
Summary: Severe COVID-19 patients exhibit an increased risk of thromboembolic events, with evidence of microthrombosis in the lungs of deceased patients. The study found a significant alteration of the VWF-ADAMTS13 axis in COVID-19 patients, with an elevated VWF:Ag to ADAMTS13 activity ratio strongly associated with disease severity, enhancing the hypercoagulable state and risk of microthrombosis in these patients.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Multidisciplinary Sciences
Kanwal Singh, Andrew C. Kwong, Hasam Madarati, Sharumathy Kunasekaran, Taylor Sparring, Alison E. Fox-Robichaud, Patricia C. Liaw, Colin A. Kretz
Summary: The study found that in septic patients, ADAMTS13 activity and antigen were reduced, while VWF antigen was elevated, with non-septic patients showing milder changes. These abnormalities persisted throughout the ICU stay and discharge in all patient cohorts, potentially contributing to a prothrombotic state in sepsis patients.
Article
Hematology
Peter L. Turecek, Rachel C. Peck, Savita Rangarajan, Christopher Reilly-Stitt, Michael A. Laffan, Rashid Kazmi, Izabela James, Ahilanandan Dushianthan, Gerald Schrenk, Herbert Gritsch, Bruce M. Ewenstein, Bjorn Mellgard, Wolfhard Erdlenbruch, Nisha Jain, Nikolaus B. Binder, Andrew D. Mumford
Summary: Thrombosis is common in severe COVID-19 patients, with an imbalance of VWF/ADAMTS13 implicated in its pathogenesis. Correction of this imbalance through rADAMTS13 may help restore hemostatic balance and potentially serve as a therapeutic approach in severe COVID-19 cases.
THROMBOSIS RESEARCH
(2021)
Editorial Material
Hematology
Jeannie Callum, Philippe Begin, Erin Jamula, Yang Liu, Amie T. Kron, Marie-Christine Auclair, Melissa Cushing, Donald M. Arnold
Summary: The CONCOR-1 trial, addressing the use of convalescent plasma for COVID-19 patients, was successfully conducted with the help of various measures and preparations. Valuable lessons were learned from this experience, providing insights for future pandemic research.
TRANSFUSION MEDICINE
(2023)
Article
Hematology
Laura M. M. Venier, Bianca Clerici, Anna-Lise Bissola, Dimpy Modi, Stefan D. D. Jevtic, Michael Radford, Syed Mahamad, Ishac Nazy, Donald M. M. Arnold
Summary: VITT is a prothrombotic disorder caused by anti-PF4 antibodies that activate platelets and neutrophils, resulting in thrombosis. HIT is a related disorder mediated by anti-PF4, with similar pathophysiology and clinical manifestations but different triggers (heparin vs adenoviral vector vaccine). Both VITT and HIT usually present with thrombocytopenia and thrombosis, but VITT has a significantly higher risk of thrombosis occurring in unusual anatomical sites. Diagnostic accuracy differs between HIT and VITT, with ELISAs being more specific for VITT and platelet activation assays requiring the addition of PF4. Anticoagulation with non-heparin anticoagulants is the treatment for VITT and HIT, although heparin may be considered for VITT if no other options are available.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2023)
Article
Cell Biology
Caroline Gabe, Yang Liu, Joanne Duncan, Melanie St John, Kayla J. J. Lucier, David Kimmel, John G. G. Kelton, Donald M. M. Arnold
Summary: This study found that approximately 14.3% of ITP patients had T-LGL, while the prevalence of T-LGL in patients with nonimmune thrombocytopenia was lower. ITP patients with T-LGL had a more severe form of the disease and were less responsive to treatment.
Review
Hematology
Syed Mahamad, Dimpy Modi B.Tech, Hanny Al-Samkari, Adam Cuker, Jenny M. Despotovic, Joseph E. Italiano, Michele P. Lambert, Eun-Ju Lee, Matthew T. Rondina, Michelle Sholzberg, Caroline Kruse, Mark Larche, Ishac Nazy, Matthew S. Miller, Donald M. Arnold
Summary: The inaugural McMaster Immune Thrombocytopenia (ITP) Summit was held virtually in 2021 to address the challenges in diagnosing ITP and gaps in understanding ITP mechanisms. The Summit included educational sessions covering 8 topics to inform future research priorities. Research priorities identified from the Summit include investigating platelet production as a target for ITP treatments, characterizing antigen processing on platelets, studying the interaction between megakaryocytes and the immune system, and improving platelet antibody testing methods.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2023)
Review
Hematology
Susan R. Kahn, Donald M. Arnold, Caterina Casari, Karl C. Desch, Katrien M. J. Devreese, Emmanuel J. Favaloro, Florian Gaertner, Samantha C. Gouw, Paolo Gresele, Arjan W. Griffioen, Lukas Heger, R. Manjunatha Kini, Shrey Kohli, Avi Leader, Ton Lisman, Marie Lordkipanidze, Eric Mullins, Helen Chioma Okoye, Rachel P. Rosovsky, Isabelle I. Salles-Crawley, Rita Selby, Michelle Sholzberg, David Stegner, Francesco Violi, Angela C. Weyand, Suzan Williams, Ze Zheng
Summary: The Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held in Montreal, Canada from June 24-28, 2023. The conference showcased cutting-edge advances in various scientific fields related to thrombosis and haemostasis, with a special focus on immuno-thrombosis. The congress covered a wide range of topics including arterial thromboembolism, coagulation and natural anticoagulants, diagnostics and omics, and women's health.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2023)
Review
Hematology
Donald M. Arnold, Bianca Clerici, Ekaterina Ilicheva, Waleed Ghanima
Summary: Immune thrombocytopenia (ITP) is an autoimmune disorder with immune-mediated thrombocytopenia and bleeding risk. Some patients are considered refractory to treatment, but the meaning of 'refractory' has become ambiguous. Experts proposed a new definition for refractory ITP, and initial data from registries showed a range of refractory patients.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Medicine, General & Internal
Deborah M. Siegal, Emilie P. Belley-Cote, Shun Fu Lee, Stephen Hill, Frederick D'Aragon, Ryan Zarychanski, Bram Rochwerg, Michael Chasse, Alexandra Binnie, Kimia Honarmand, Francois Lauzier, Ian Ball, Waleed Al-Hazzani, Patrick Archambault, Erick Duan, Kosar Khwaja, Francois Lellouche, Paul Lysecki, Francois Marquis, Jean-Francois Naud, Jason Shahin, Jennifer Shea, Jennifer L. Y. Tsang, Han Ting Wang, Mark Crowther, Donald M. Arnold, Emily Di Sante, Gladys Marfo, Tanya Kovalova, Sylvanus Fonguh, Jessica Vincent, Stuart J. Connolly
Summary: The use of small-volume blood collection tubes in the ICU may decrease RBC transfusions without affecting laboratory analysis.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Editorial Material
Medicine, General & Internal
Syed Mahamad, Donald M. Arnold
Article
Hematology
Kiarash Riazi, Mark Ly, Rebecca Barty, Jeannie Callum, Donald M. Arnold, Nancy M. Heddle, Douglas G. Down, Davinder Sidhu, Na Li
Summary: This study utilized electronic health records to uncover utilization subgroups among immunoglobulin (Ig) recipients in Canada. The findings provide valuable insights for resource planning and demand forecasting.
Meeting Abstract
Hematology
N. Li, K. Riazi, D. Arnold, D. Sidhu, R. Barty, N. Heddle, J. Callum, D. Down
Meeting Abstract
Hematology
D. Arnold, K. Eisa, P. Keith, D. Morrison, S. Ning, A. Shih, S. Waserman, K. Webert, M. Yan, N. Heddle
Article
Hematology
Theodore E. Warkentin, Donald M. Arnold, Jo-Ann I. Sheppard, Jane C. Moore, John G. Kelton, Ishac Nazy
Summary: This study compared the profiles of anti-PF4 vs anti-PF4/H antibodies using solid-EIA and fluid-EIA among different disorders. The results showed that the fluid-EIA profiles of classic HIT (cHIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT) were opposite to those of solid-EIA, while autoimmune HIT (aHIT) and spontaneous HIT (SpHIT) patients exhibited reactivity in both fluid-EIA and solid-EIA against PF4. Moreover, a minority of SpHIT and aHIT patients presented clinical and serologic profiles resembling VITT.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Letter
Hematology
Syed Mahamad, Na Li, Donald M. Arnold
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Meeting Abstract
Clinical Neurology
R. Fox, J. Oh, D. Arnold, S. Syed, Z. Xu, T. Turner, A. Traboulsee, D. Reich
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Meeting Abstract
Clinical Neurology
G. Giovannoni, J. Foley, G. Defer, L. Zhovtis Ryerson, J. Cohen, D. Arnold, H. Butzkueven, G. Cutter, J. Killestein, H. Wiendl, S. Sinks, J. Steverson, L. Dsilva, M. Monine, J. Sohn, E. Ferraro, T. Lasky
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
