Journals Journal of Thrombosis and Haem...

Journal of Thrombosis and Haemostasis : JTH
James E Chessum, Shana A Shaya, Dana Rajab, Ali Aftabjahani, Ji Zhou, Jeffrey I Weitz, Peter L Gross, Paul Y Kim
BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI) levels are positively correlated with the risk of thrombosis. The mechanism of how TAFI affects venous thromboembolism (VTE) remains uncertain. In addition, the role of sex on the risk of VTE has also been studied. However, their association also remains unclear. We investigate how TAFI and/or sex affects venous thrombus stability and consequent pulmonary embolism. METHODS: FeCl3 -induced thrombi were formed within femoral veins of male and female wild-type (WT) or TAFI-knockout (Cpb2-/- ) mice...
September 24, 2023: Journal of Thrombosis and Haemostasis: JTH
Jonathan Mäder, Christina C Rolling, Minna Voigtländer, Anita Schulenkorf, Carina Lehr, Judith Regenhardt, Carsten Bokemeyer, Lennart Beckmann, Florian Langer
BACKGROUND: Cancer-associated thrombosis (CAT) is a frequent complication in patients with malignancies. While FXI/FXIa inhibition is efficacious in preventing postoperative venous thromboembolism, its role in tumor cell-induced coagulation is less defined. OBJECTIVES: We thus aimed to provide mechanistic insights into FXI/FXIa inhibition in tumor cell-induced coagulation activation. METHODS: Procoagulant activity (PCA) of four different tissue factor (TF) expressing tumor cell lines was analyzed by single-stage clotting and thrombin generation assay in the presence of a FXIa inhibitor, BMS-262084 (BMS), an inhibitory FXI antibody (anti-FXI), or peak and trough concentrations of rivaroxaban or tinzaparin...
September 24, 2023: Journal of Thrombosis and Haemostasis: JTH
Manuel Salzmann, Patrizia Gibler, Patrick Haider, Mira Brekalo, Roberto Plasenzotti, Thomas Filip, Rebecca Nistelberger, Boris Hartmann, Johann Wojta, Christian Hengstenberg, Bruno K Podesser, Julia B Kral-Pointner, Philipp J Hohensinner
BACKGROUND: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells and highly procoagulant. Anticoagulation treatment was shown to reduce in-hospital mortality, indicating thromboinflammatory complications. However, little data is available on the involvement of NETs in secondary events after virus clearance, which can lead to persistent lung damage and post-acute sequelae with chronic fatigue and dyspnea...
September 23, 2023: Journal of Thrombosis and Haemostasis: JTH
Julie Jaffray, Maua Mosha, Brian Branchford, Neil A Goldenberg, Michael Silvey, Stacy E Croteau, John H Fargo, James D Cooper, Nihal Bakeer, Amy Stillings, Emily Krava, Guy Young, Ernest K Amankwah
No abstract text is available yet for this article.
September 21, 2023: Journal of Thrombosis and Haemostasis: JTH
Dino Mehic, Daniel Kraemmer, Alexander Tolios, Julia Bücheler, Peter Quehenberger, Helmuth Haslacher, Cihan Ay, Ingrid Pabinger, Johanna Gebhart
BACKGROUND: In patients with a mild-to-moderate bleeding disorders (MBD), von Willebrand disease (VWD) is diagnosed at von Willebrand factor (VWF) levels ≤50 IU/dL. Although VWF levels are unstable, repeated testing for VWD diagnosis is not necessarily advised in recent guidelines. AIMS: To analyze the relevance of repeated VWF testing to diagnose VWD in MBD patients. METHODS: Data of 277 MBD patients from the Vienna bleeding biobank with at least two separate assessments of VWF antigen (VWF:Ag) and activity (VWF:Act) were analyzed...
September 21, 2023: Journal of Thrombosis and Haemostasis: JTH
Nasim Shahidi Hamedani, Anouk Anna Marie Therese Donners, Matthijs van Luin, Simone Gasper, Heiko Rühl, Claudia Klein, Thilo Albert, Mohsin El Amrani, Bernd Pötzsch, Johannes Oldenburg, Jens Müller
BACKGROUND: Accurate measurement of emicizumab in the presence of FVIII is required in severe HA patients treated with emicizumab and additional need for FVIII substitution or in emicizumab prophylaxis in patients with acquired or moderate to mild HA. However, the presence of FVIII potentially biases the results. OBJECTIVE: To assess the impact of plasma FVIII activity on determined emicizumab levels and to evaluate different strategies for correction for or pre-analytical inhibition of FVIII...
September 21, 2023: Journal of Thrombosis and Haemostasis: JTH
Magdalena Gierula, Victoria M Noakes, Isabelle I Salles-Crawley, James T B Crawley, Josefin Ahnström
BACKGROUND: For maximal TFPIα functionality, two synergistic cofactors, protein S and FV-short, are required. Both interact with TFPIα, protein S through Kunitz 3 residues Arg199/Glu226 and FV-short with the C-terminus. How these interactions impact the synergistic enhancement remains unclear. OBJECTIVES: Determine the importance of the TFPIα-protein S and TFPIα-FV-short interactions for TFPIα enhancement. METHODS: TFPIα variants unable to bind protein S (K3m [R199Q/E226Q]) or FV-short (ΔCT [aa 1-249]) were generated...
September 20, 2023: Journal of Thrombosis and Haemostasis: JTH
Daniel Kraemmer, Oliver Königsbrügge, Florian Moik, Brigitte Wildner, Cihan Ay, Ingrid Pabinger
BACKGROUND: With population pharmacokinetic (PK) modeling more readily available and PK-guided prophylaxis endorsed by current hemophilia guidelines, we conducted a systematic review to summarize current evidence in the literature. OBJECTIVE: To assess the efficacy of PK-guided compared to non-PK-guided prophylaxis. METHODS: We did not restrict inclusion to specific study design labels and included all studies consisting of at least one distinct cohort arm receiving PK-guided prophylaxis...
September 20, 2023: Journal of Thrombosis and Haemostasis: JTH
Andrea Lee Cervi, Darrin Applegate, Scott M Stevens, Scott C Woller, Lisa M Baumann Kreuziger, Kavya Punchhalapalli, Tzu-Fei Wang, Ramon Lecumberri, Kaity Greco, Yuxin Bai, Samantha Bolger, Stephanie Fontyn, Sam Schulman, Gary Foster, James Demetrios Douketis
BACKGROUND: In patients with acute deep vein thrombosis (DVT) treated with catheter-based thrombolysis and venous stenting, post-stenting anticoagulant management is uncertain. METHODS: We created an international registry of patients with leg DVT from 2005-2019 who received venous stents as part of their acute management. We collected data on baseline clinical characteristics and pre-and post-venous stent antithrombotic therapy. RESULTS: We studied 173 patients with venous stents: 101 (58%) were ≤50 years old; 105 (61%) were female; and 128 (74%) had risk factors for thrombotic disease...
September 20, 2023: Journal of Thrombosis and Haemostasis: JTH
Justine H Ryu, Kenneth A Bauer, Sol Schulman
Type 2 Normandy von Willebrand disease (type 2N VWD) is a rare qualitative defect in von Willebrand factor (VWF) that results in impaired factor VIII (FVIII) binding and consequently reduced FVIII levels. Current perioperative strategies require VWF concentrates to attain durable hemostatic FVIII levels. This case highlights the successful perioperative management of a 78-year-old female with type 2N VWD and coronary artery disease utilizing efanesoctocog alfa, a novel long-acting recombinant FVIII product approved for hemophilia A...
September 19, 2023: Journal of Thrombosis and Haemostasis: JTH
Megan Simpson, Anuj Narwal, Eric West, Jill Martin, Catherine N Bagot, Andrew R Page, Henry G Watson, Claire S Whyte, Nicola J Mutch
BACKGROUND: Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT) is a rare syndrome associated with adenoviral vector vaccines for COVID-19. The syndrome is characterised by thrombosis, anti-platelet factor 4 (PF4) antibodies, thrombocytopenia, high D-dimer and hypofibrinogenemia. OBJECTIVE: To investigate abnormalities in fibrinolysis that contribute to the clinical features of VITT. METHODS: Plasma from 18 suspected VITT cases was tested for anti-PF4 by ELISA and characterised as meeting criteria for VITT (11/18) or deemed unlikely (7/18; non-VITT)...
September 19, 2023: Journal of Thrombosis and Haemostasis: JTH
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
BACKGROUND: Coagulation factor VIII (FVIII) and von Willebrand factor (VWF) circulate as a noncovalent complex, but each has its distinct functions. Binding of FVIII to VWF results in a prolongation of FVIII's half-life in circulation and modulates FVIII's immunogenicity during hemophilia therapy. However, the biological effect of FVIII and VWF interaction on VWF homeostasis is not fully understood. METHODS: Mouse models, recombinant FVIII infusion, and hemophilia A patients on a high dose FVIII for immune tolerance induction therapy or emicizumab for bleeding symptoms were included to address this question...
September 17, 2023: Journal of Thrombosis and Haemostasis: JTH
Toshiaki Iba, Julie Helms, Matthew D Neal, Jerrold H Levy
Disseminated intravascular coagulation can occur due to different causes but commonly following sepsis. Trauma-induced coagulopathy (TIC) occurs on hospital arrival in approximately 25% of seriously injured patients who initially presents with impaired hemostasis and a bleeding phenotype that can later progress to a prothrombotic phase. Following traumatic injury, ineffective hemostasis is driven by massive blood loss, tissue damage, and hyperfibrinolysis. This initial impaired hemostasis continues until surgical or other management strategies not only to stop the causes of hemorrhage but also progresses to a prothrombotic and hypofibrinolytic state, also termed fibrinolytic shutdown...
September 16, 2023: Journal of Thrombosis and Haemostasis: JTH
Tina Manon-Jensen, Srilatha Tangada, Cecilie Bager, Pratima Chowdary, Robert Klamroth, Annette von Drygalski, Jerzy Windyga, Miguel Escobar, Peder Frederiksen, Werner Engl, Bruce Ewenstein, Morten Karsdal
BACKGROUND: Hemophilia patients with recurrent hemarthroses develop hemophilic arthropathy (HA). Regular prophylaxis with factor VIII (FVIII) can reduce HA, but there is a need for objective outcome measures to evaluate treatment efficacy. METHODS: Joint remodeling was assessed by analyzing serum levels of collagen remodeling products at baseline and months 3, 6, 9, and 12 in a 98 patient subset receiving pharmacokinetics-guided prophylaxis with rurioctocog alfa pegol, targeting FVIII trough levels of 1-3 IU/dL or 8-12 IU/dL (PROPEL study, NCT0285960)...
September 15, 2023: Journal of Thrombosis and Haemostasis: JTH
Michael M Glenzer, Momade Correia, Virgilio Nhantumbo, Richard Fw Barnes, Elvira Luis, Ines Boaventura, Nelia Manguele, Patricia Silva, Annette von Drygalski
INTRODUCTION: Estimates indicate ≈500-1,000 maternal deaths per 100,000 live births in Sub-Saharan Africa (SSA) (vs ≈5-20 in developed countries). Postpartum hemorrhage (PPH) seems a major contributor to maternal mortality (MM), but there are no comprehensive data for the region. METHODS: We collected prospective data on MM, PPH, and associated risk factors in metropolitan Mozambique. We recorded consecutive deliveries at Maputo Central Hospital between February 2019 and January 2021...
September 12, 2023: Journal of Thrombosis and Haemostasis: JTH
Andra H James, Paula D James
Women, or people with a uterus, are vulnerable to both normal and abnormal bleeding. During the reproductive years, the uterus is prepared physiologically to accept an embryo and support its growth and development during pregnancy, or in the absence of implantation of an embryo, recycle through the process of menstruation and accept an embryo a month or so later. If fertilization takes place and an embryo or embryos implant in the uterus, the fetal trophoblast, or outer cell layer of the embryo, invades and dilates the maternal spiral arteries and forms the placenta...
September 12, 2023: Journal of Thrombosis and Haemostasis: JTH
Ratnashree Biswas, Emily Boyd, Nathan Eaton, Agata Steenackers, Marie L Schulte, Friedrich Reusswig, Hongyin Yu, Caleb Drew, Walter H A Kahr, Qizhen Shi, Markus Plomann, Karin M Hoffmeister, Hervé Falet
BACKGROUND: Upon vessel injury, platelets adhere to exposed matrix constituents via specific membrane receptors, including the von Willebrand factor receptor GPIb-IX-V complex and integrins β1 and β3. In platelets, the F-BAR protein PACSIN2 associates with the cytoskeletal and scaffolding protein filamin A (FlnA), linking GPIbα and integrins to the cytoskeleton. OBJECTIVES: Here we investigated the role of PACSIN2 in platelet function. METHODS: Platelet parameters were evaluated in mice lacking PACSIN2 and platelet integrin β1...
September 5, 2023: Journal of Thrombosis and Haemostasis: JTH
David M Smadja, Elisa Rossi, Skerdi Haviari, Ivan Bieche, Audrey Cras, Pascale Gaussem
BACKGROUND: The involvement of thrombin receptor PAR1 in blood vessel development has been largely demonstrated in knockout mice; however, its implication in adult mouse angiogenesis seems very moderate. AIMS: To explore the potential relationships between PAR1, stemness and angiogenic properties of endothelial colony forming cells (ECFCs). METHODS AND RESULTS: PAR1 activation on ECFCs using the selective PAR1 activating peptide induced a significant decrease in CD133 expression (RTQ-PCR analysis)...
September 5, 2023: Journal of Thrombosis and Haemostasis: JTH
Evelien Krumb, Nishita Mehta, Ciaran Hutchinson, Bilal Jradeh, Ewa Jaslowska, Keith Gomez, Rezan Abdul Kadir
In patients with severe congenital factor X (FX) deficiency, spontaneous intracranial haemorrhage (ICH) is particularly frequent in early childhood. We describe a case of fetal death at 26 weeks due to massive ICH. Gene panel analysis of post-mortem samples revealed homozygosity for a pathological F10 gene variant (c.1210T>C, p.Cys404Arg), which impedes correct folding of the catalytic serine protease domain and therefore causes a significant reduction in FX levels. The parents, not consanguineous but of the same ethnic community, were found to be heterozygous for this variant and did not have any personal or family history of abnormal bleeding...
September 5, 2023: Journal of Thrombosis and Haemostasis: JTH
Alexandre Guy, Geoffrey Garcia, Virginie Gourdou-Latyszenok, Laura Wolff-Thrombini, Lara Josserand, Quentin Kimmerlin, Simon Favre, Badr Kilani, Caroline Marty, Yacine Boulaftali, Sylvie Labrouche-Colomer, Olivier Mansier, Chloé James
BACKGROUND: Neutrophils participate in the pathogenesis of thrombosis through the formation of neutrophil extracellular traps (NETs). Thrombosis is the main cause of morbidity and mortality in patients with myeloproliferative neoplasms (MPNs). Recent studies have shown an increase in NET formation (NETosis) both in patients with JAK2V617F neutrophils and in mouse models, and reported the participation of NETosis in the pathophysiology of thrombosis in mice. OBJECTIVES: This study investigated whether JAK2V617F neutrophils are sufficient to promote thrombosis or whether their cooperation with other blood cell types is necessary...
September 5, 2023: Journal of Thrombosis and Haemostasis: JTH
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