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
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
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)
Review
Biochemistry & Molecular Biology
Juan A. De Pablo-Moreno, Luis Javier Serrano, Luis Revuelta, Maria Jose Sanchez, Antonio Liras
Summary: The vascular endothelium plays a crucial role in hemostasis, maintaining a delicate balance between procoagulant and anticoagulant proteins, as well as fibrinolytic and antifibrinolytic factors. Coagulation disorders can be caused by mutations in coagulation factors or disruptions in the regulatory mechanisms. Treatment options include replacement and nonreplacement therapies, as well as administration of antifibrinolytic agents. Targeted therapies, such as monoclonal antibodies and interfering RNA therapies, are also being developed. The treatment approach for thrombophilia, disseminated intravascular coagulation, and severe thrombophilia varies depending on the specific condition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Jerzy Windyga, Benoit Guillet, Lucia Rugeri, Alexandra Fournel, Ewa Stefanska-Windyga, Valerie Chamouard, Sonia Pujol, Celine Henriet, Francoise Bridey, Claude Negrier
Summary: This study evaluated the hemostatic efficacy and safety of continuous infusion of pdFVIII and pdVWF in patients with HA and VWD undergoing surgery.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Eugenia Biguzzi, Filippo Castelli, Willem M. Lijfering, Suzanne C. Cannegieter, Jeroen Eikenboom, Frits R. Rosendaal, Astrid van Hylckama Vlieg
Summary: VWF:Ag and FVIII:C levels increase with age, with carriers of non-O blood group showing a steeper increase that is mediated by acquired factors. Differences in increase between blood groups are annulled after adjustment for acquired factors.
THROMBOSIS RESEARCH
(2021)
Article
Physiology
Helena A. Turton, Josephine Pickworth, Gordon G. Paterson, Allan Lawrie, J. Kenneth Baillie, A. A. Roger Thompson
Summary: High altitude exposure leads to increased levels of plasma P-selectin and vWF, with a strong positive correlation between the two markers. These changes are not solely attributed to an increase in platelet count.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Po-Chia Chen, Fabian Kutzki, Angelika Mojzisch, Bernd Simon, Emma-Ruoqi Xu, Camilo Aponte-Santamaria, Kai Horny, Cy Jeffries, Reinhard Schneppenheim, Matthias Wilmanns, Maria A. Brehm, Frauke Graeter, Janosch Hennig
Summary: Von Willebrand disease is a bleeding disorder associated with mutations in the VWF gene. This study investigates the structure and dynamics of the C6 domain and the G2705R variant in C6, using nuclear magnetic resonance spectroscopy, molecular dynamics simulations and aggregometry. The findings show that the G2705R mutation destabilizes VWF by promoting hinging between the subdomains of C6.
JOURNAL OF STRUCTURAL BIOLOGY
(2022)
Article
Hematology
Jameel Abdulrehman, Yonah C. Ziemba, Peihong Hsu, Elizabeth M. Van Cott, Elizabeth A. Plumhoff, Piet Meijer, Martine J. Hollestelle, Rita Selby
Summary: The study compared the imprecision among various VWD assays and methods, finding that VWF antigen had the lowest imprecision while collagen binding activity had the highest. There was excellent consensus among the assays for correct classification of sample results, but consensus on final interpretation decreased as sample complexity increased.
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
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
Cardiac & Cardiovascular Systems
Artur Saldanha, Maria Eduarda Veiga, Erica Okazaki, Cynthia Rothschild, Gracia Martinez, Vanderson Rocha, Fernanda A. Orsi, Paula Villaca
Summary: MGUS is a plasma cell disorder that can precede multiple myeloma. AVWS is a rare bleeding disorder that can occur in patients with MGUS. Eradication of the monoclonal paraprotein may be necessary to treat bleeding complications due to MGUS-associated AVWS.
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
(2023)
Article
Cardiac & Cardiovascular Systems
Ingrid Bekono-Nessah, Alex Rosenburg, Christopher T. Bowles, Fernando Riesgo-Gil, Ulrich Stock, Richard R. Szydlo, Mike Laffan, Deepa J. Arachchillage
Summary: Major bleeding and thrombosis significantly increase the 1-year mortality in HVAD patients. Optimal perioperative hemostasis and anticoagulation remain crucial for HVAD patients.
Article
Hematology
Hithin Noble, Christina Crossette-Thambiah, Zain Odho, Nilanthi Karawitage, Karen Logan, Charis Pericleous, Mike Laffan, Deepa J. Arachchillage
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2023)
Article
Pharmacology & Pharmacy
Alexander J. Robbins, Nur Amalina Che Bakri, Edward Toke-Bjolgerud, Aaron Edwards, Asha Vikraman, Cathy Michalsky, Michael Fossler, Nana-Marie Lemm, Savviz Medhipour, William Budd, Athanasia Gravani, Lisa Hurley, Vikas Kapil, Aimee Jackson, Dagan Lonsdale, Victoria Latham, Michael Laffan, Neil Chapman, Nichola Cooper, Richard Szydlo, Joseph Boyle, Katrina M. Pollock, David Owen
Summary: COVID-19 causes significant thrombosis and coagulopathy, with elevated D-dimer as an adverse outcome predictor. The mechanism of this coagulopathy is not clear, but it may involve the accumulation of pro-inflammatory angiotensin-II due to the loss of angiotensin-converting enzyme 2 activity. A study investigated the effect of TRV027, a synthetic angiotensin-1-7 analogue, on D-dimer levels in 30 hospitalized COVID-19 patients. The results showed a numerical decrease in D-dimer in the TRV027 group, but this difference did not reach statistical significance.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Hematology
Tom Burke, Idaira Rodriguez-Santana, Pratima Chowdary, Randall Curtis, Kate Khair, Michael Laffan, Paul Mclaughlin, Declan Noone, Brian O'Mahony, John Pasi, Mark Skinner, Jamie O'Hara
Summary: The problem joint (PJ) concept was developed to address patient-centric needs for a more holistic assessment of joint morbidity for people with haemophilia (PwH). This study used data analysis to quantify the humanistic burden of PJs in PwH and further validated the PJ outcome measure. The results showed that PJs are associated with decreased health-related quality of life and overall work productivity loss in PwH. Therefore, the importance of PJs should be considered in clinical and health policy assessments of joint health.
Review
Biochemistry & Molecular Biology
Deepa J. Arachchillage, Mike Laffan, Charis Pericleous
Summary: Antiphospholipid syndrome (APS) is a highly prothrombotic disorder caused by thrombo-inflammatory antiphospholipid antibodies (aPL) that lead to thrombosis through various mechanisms. Obstetric complications in APS are a result of placental thrombosis, inflammation, and complement activation. While anticoagulation is the main treatment, it may not effectively prevent thrombosis recurrence in some patients, especially those with triple positive aPL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Deepa Arachchillage, Indika Rajakaruna, Zain Odho, Mike Makris, Mike Laffan
Summary: The controversy of post-discharge thromboprophylaxis in COVID-19 patients remains. This observational study across 26 NHS Trusts aimed to determine the impact of thromboprophylaxis on hospital acquired thrombosis (HAT) in discharged patients. The study found no difference in HAT between patients discharged with and without thromboprophylaxis, but increasing age and smoking significantly increased the risk of HAT.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Mike Laffan, Gary Benson, Cathy Farrelly, Keith Gomez, April Jones, Rhona Maclean, James O'Donnell, Michelle Lavin
Summary: Von Willebrand Disease (VWD) is a common inherited bleeding disorder, but awareness and understanding of the disease lags behind other bleeding disorders, causing delays in diagnosis and treatment. Updated national guidelines are needed to improve the management of VWD and provide equitable care for both men and women. Through a survey and analysis conducted by a panel of experts, eight recommendations were derived to enhance the detection and management of VWD.
Letter
Critical Care Medicine
Charlotte A. Bradbury, Patrick R. Lawler, Bryan J. McVerry, Ryan Zarychanski, REMAP C A P Investigators
INTENSIVE CARE MEDICINE
(2023)
Article
Medicine, General & Internal
J. Mahlangu, R. Kaczmarek, A. von Drygalski, S. Shapiro, S. -C. Chou, M. C. Ozelo, G. Kenet, F. Peyvandi, M. Wang, B. Madan, N. S. Key, M. Laffan, A. L. Dunn, J. Mason, D. V. Quon, E. Symington, A. D. Leavitt, J. Oldenburg, H. Chambost, M. T. Reding, K. Jayaram, H. Yu, R. Mahajan, K. -M. Chavele, D. B. Reddy, J. Henshaw, T. M. Robinson, W. Y. Wong, S. W. Pipe
Summary: This study demonstrates the long-term effectiveness and safety of valoctocogene roxaparvovec therapy in reducing bleeding events in men with severe hemophilia A. The pharmacokinetic modeling suggests a half-life of 123 weeks for the transgene-derived factor VIII production system. Models also indicate a similar relationship between factor VIII activity and bleeding episodes as observed in individuals with mild-to-moderate hemophilia A using epidemiologic data.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Cell Biology
Joanne L. Mitchell, Dalia Khan, Rekha H. Rana, Neline Kriek, Amanda J. Unsworth, Tanya Sage, Alexander P. Bye, Michael Laffan, Susan Shapiro, Anjan Thakurta, Henri Grech, Karthik Ramasamy, Jonathan M. Gibbins
Summary: This pilot study demonstrated that patients with MGUS, SM and MM have increased platelet reactivity and prothrombotic potential, which is further exacerbated by treatment with Lenalidomide.
Article
Hematology
Giulia Simini, Frances Akor, Richard Szydlo, Michael Laffan, Deepa R. J. Arachchillage
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2023)
Article
Hematology
Nicola S. Curry, Ross Davenport, Henna Wong, Christine Gaarder, Par Johansson, Nicole P. Juffermans, Marc Maegele, Jakob Stensballe, Karim Brohi, Mike Laffan, Simon J. Stanworth
Summary: This study reports coagulation profiles stratified by age and finds an association between age and hemostatic capability. Although similar patterns of coagulation abnormalities are observed across age groups following severe injury/shock, thresholds for single clotting factors differ. These age-related differences may need to be considered in clinical treatments (e.g., transfusion therapy).
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Deepa J. Arachchillage, Anna Weatherill, Indika Rajakaruna, Mihaela Gaspar, Zain Odho, Graziella Isgro, Lenka Cagova, Lucy Fleming, Stephane Ledot, Mike Laffan, Richard Szydlo, Rachel Jooste, Ian Scott, Alain Vuylsteke, Hakeem Yusuff
Summary: Thrombosis and major bleeding are common complications in V-V ECMO patients and significantly increase mortality. Age and elevated creatinine level are associated with increased mortality, while the type of thrombosis has different effects on mortality.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Meeting Abstract
Hematology
Deepa J. Arachchillage, Indika Rajakaruna, Mike Laffan, Richard Szydlo, Zain Odho, Ian Scott, Stephane Ledot, Alain Vuylsteke, Hakeem Yusuff
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Meeting Abstract
Hematology
Giulia Simini, Saravanan Vinayagam, Nilanthi Karawitage, Golzar Mobayen, Anupama Krishnamoorthi, Andrew James Innes, Michael Laffan, Deepa Jayakody Arachchillage
BRITISH JOURNAL OF HAEMATOLOGY
(2023)