Journals Journal of Thrombosis and Haem...

Journal of Thrombosis and Haemostasis : JTH
Gao-Chao Zhang, Ye-Jun Wu, Feng-Qi Liu, Qi Chen, Xue-Yan Sun, Qing-Yuan Qu, Hai-Xia Fu, Xiao-Jun Huang, Xiao-Hui Zhang
BACKGROUND AND OBJECTIVES: The sympathetic nerve is known to regulate immune responses in autoimmunity. Aberrant T cell immunity plays a vital role in immune thrombocytopenia (ITP) pathogenesis. The spleen is the primary site of platelet destruction. However, little is known whether and how splenic sympathetic innervation and neuroimmune modulation contribute to ITP pathogenesis. We hypothesized that decreased distribution of sympathetic nerve in the spleen of ITP mice contributed to abnormal T cell immunity and promoted ITP development, which could be reversed by β2-adrenergic receptor (β2-AR) agonists...
March 25, 2023: Journal of Thrombosis and Haemostasis: JTH
Jecko Thachil, Jean M Connors, Johnny Mahlangu, Michelle Sholzberg
Hemophilia is classified into mild, moderate, and severe based on coagulation factor activity levels. Factor replacement and prophylaxis regimens in persons with hemophilia (PwH) have helped to reduce bleeding and its related complications. With several newer treatments, some already approved and others soon to be, there may be a need to consider health-related quality of life in addition to bleed prevention as the goals of comprehensive care provision in PwH. In this article, we discuss the reasons why such an approach may be relevant and call for the International Society of Thrombosis and Haemostasis to revisit the current classification of hemophilia...
March 25, 2023: Journal of Thrombosis and Haemostasis: JTH
Bethany Samuelson Bannow, Jerome J Federspiel, David E Abel, Logan Mauney, Rachel P Rosovsky, Shannon M Bates
The care of pregnant persons with/at risk for venous thromboembolism is complex and often challenging. While guidelines have been published regarding the use of specific therapies, such as anticoagulants; in this population, none have provided guidance on how to coordinate multidisciplinary care of these patients. Here, we provide an expert consensus on the role of various providers in the care of this patient population, as well as necessary resources and suggestions for best practices.
March 25, 2023: Journal of Thrombosis and Haemostasis: JTH
Ejaife O Agbani, Lorraine Chow, Joshua Nicholas, Leslie Skeith, Prism Schneider, Alexander Gregory, Etienne Mahe, Lisa Yamaura, Daniel Young, Antoine Dufour, Padma Polash Paul, Andrew M Walker, Priyanka G Mukherjee, Alastair W Poole, Man-Chiu Poon, Adrienne Lee
BACKGROUND: Preeclampsia is a hypertensive disorder in pregnancy that results in significant adverse maternal and neonatal outcomes. Platelet activation is present in preeclampsia and contributes to the thrombo-haemorrhagic states of the disorder. However, the mechanisms which initiate and/or sustain platelet activation in preeclampsia are ill-defined. METHODS: In this quantitative observational study, we analysed platelet procoagulant membrane dynamics in preeclampsia patients (n=21) compared to age-matched normotensive pregnancies (n=20), gestational hypertension (n=10), and non-pregnant female controls (n=19)...
March 22, 2023: Journal of Thrombosis and Haemostasis: JTH
Marie-Claude Pelland-Marcotte, Valérie Bouchard, Évelyne Bégin, Eve Bouhêlier, Raoul Santiago, Paul Monagle
BACKGROUND: Accurate prediction of the individual risk of venous thromboembolism (VTE) remains suboptimal in children, and biomarkers are currently not used to stratify the risk of VTE in children. OBJECTIVES: To assess which biological or radiological biomarkers may predict VTE or VTE complications in children. PATIENTS/METHODS: A literature search was performed for peer-reviewed publications (1990-2022). We included studies addressing the use of biomarkers for patients aged 29 days to 18 years old to predict VTE or VTE complications, including but not limited to TE-related death, VTE recurrence or post-thrombotic syndrome...
March 21, 2023: Journal of Thrombosis and Haemostasis: JTH
David S Paul, Tasha N Blatt, Wyatt J Schug, Emily G Clark, Tomohiro Kawano, Nigel Mackman, Sebastian Murcia, Kathryn O Poe, Jean Marie N Mwiza, T Kendall Harden, Wolfgang Bergmeier, Robert A Nicholas
BACKGROUND: Hemostatic plug formation at sites of vascular injury is strongly dependent on rapid platelet activation and integrin-mediated adhesion and aggregation. However, to prevent thrombotic complications, platelet aggregate formation must be a self-limiting process. The second wave mediator ADP activates platelets via Gq-coupled P2Y1 and Gi-coupled P2Y12 receptors. Following ADP exposure, the P2Y1 receptor undergoes rapid phosphorylation-induced desensitization, a negative feedback mechanism thought to be critical for limiting thrombus growth...
March 21, 2023: Journal of Thrombosis and Haemostasis: JTH
Belén de la Morena-Barrio, Ángeles Palomo, José Padilla, Laura Martin-Fernandez, Juan José Rojo-Carrillo, Rosa Cifuentes, Carlos Bravo-Pérez, Pedro Garrido-Rodríguez, Antonia Miñano, Ana María Rubio, Javier Pagan, María Llamas, Vicente Vicente, Francisco Vidal, María Luisa Lozano, Javier Corral, María Eugenia de la Morena-Barrio
BACKGROUND: Congenital factor XI deficiency is a coagulopathy probably underestimated that confers antithrombotic protection. Characterization of genetic defects in F11 is mainly focused on the identification of single nucleotide variants and small insertion/deletions, as they represent up to 99% of the alterations accounting for factor deficiency, with only 3 gross gene defects of structural variants (SVs) having been described. OBJECTIVE: To identify and characterize SVs affecting F11...
March 18, 2023: Journal of Thrombosis and Haemostasis: JTH
Wei Liu, Jiaying Liu, Feng Xue, Renchi Yang, Lei Zhang
Patients with acquired hemophilia A (AHA) are prone to bleeding symptoms due to decrease of factor VIII (FVIII) activity caused by FVIII antibodies. Risk of severe bleeding in AHA is higher than that of hereditary hemophilia, so clearance of FVIII inhibitors is necessary for treatment, especially refractory AHA. Daratumumab is currently a popular monoclonal antibody for clearing plasma cells and antibodies and often used in multiple myeloma. Based on this, we report for the first time that 4 patients with AHA who were refractory to first- and second-line therapy were treated with daratumumab and achieved good responses...
March 18, 2023: Journal of Thrombosis and Haemostasis: JTH
Behnaz Pezeshkpoor, Nadja Sereda, Ann-Cristin Berkemeier, Isabell Matuschek, Nadine Schwarz, Peter L Turecek, Silvia Horneff, Claudia Klein, Georg Goldmann, Natascha Marquardt, Thilo Albert, Jens Müller, Johannes Oldenburg
BACKGROUND: The standard therapy for hemophilia A (HA) patients is the replacement with Factor VIII (FVIII) therapeutics. To overcome the limitation of the short half-life of wild-type FVIII protein, polyethylene glycol (PEG) can be coupled to therapeutic FVIII to improve pharmacokinetics. OBJECTIVES: To characterize antibodies developed against a FVIII therapeutic PEGylated with a 40 kDa PEG (40PEG-BDDFVIII ) in two mild HA patients. METHODS: An in-house bead-based immunoassay was developed to characterize and confirm the specificity of detected antibodies...
March 17, 2023: Journal of Thrombosis and Haemostasis: JTH
Anna Falanga, Marina Marchetti
Thrombosis, both venous and arterial, is a leading cause of morbidity and mortality in patients with cancer. Studies on the molecular basis of cancer-associated thrombophilia have a long story starting from the first observation of the presence of tumor cells in circulating microthrombi two centuries ago. The profound link between pathways of blood coagulation and tumor biology has been more and more unraveled, and new actors in this complex interaction have been identified. The unfavorable impact of thrombosis in a cancer patient, on which also hangs a high bleeding risk as compared to the non-cancer population, has led during years to the production of large clinical studies to adopt the best prophylaxis and treatment strategies of venous thromboembolism in different medical and surgical settings, now incorporated in dedicated international guidelines...
March 15, 2023: Journal of Thrombosis and Haemostasis: JTH
Bosko M Stojanovski, Enrico Di Cera
BACKGROUND: Current assays that monitor thrombin generation in plasma rely on fluorogenic substrates to follow the kinetics of zymogen activation, which may be complicated by substrate cleavage from other proteases. In addition, these assays depend on activation following cleavage at the R320 site of prothrombin and fail to report cleavage at the alternative R271 site that leads to shedding of the auxiliary Gla and kringle domains of prothrombin. OBJECTIVE: To develop a plasma assay that directly monitors prothrombin activation independent of fluorogenic substrate hydrolysis...
March 15, 2023: Journal of Thrombosis and Haemostasis: JTH
Dino Mehic, Georg Neubauer, Florian Janig, Alexandra Kaider, Cihan Ay, Ingrid Pabinger, Johanna Gebhart
BACKGROUND: The future bleeding risk, especially after hemostatic challenges, and thus requirement of hemostatic treatment in patients with mild-to-moderate bleeding disorders (MBD) is largely unknown. OBJECTIVE: To prospectively examine the recurrence of bleeding symptoms and clinical risk factors for future bleeding in MBD patients, including patients with bleeding disorder of unknown cause (BDUC). METHODS AND PATIENTS: Bleeding symptoms of MBD patients included in the Vienna bleeding biobank were re-evaluated at in-person follow-up visits or by mail...
March 14, 2023: Journal of Thrombosis and Haemostasis: JTH
Christina VanderPluym, Paul Esteso, Ashish Ankola, Amy Hellinger, Courtney Ventresco, Beth Hawkins, Ryan L Kobayashi, Ryan Williams, Maria A Cetatoui, Kimberlee Gauvreau, Jesse J Esch
BACKGROUND: DOAC use in pediatric cardiology is poorly defined. OBJECTIVE: We present the largest experience of apixaban use in children with heart disease, using weight- and level-based dosing. METHODS: Retrospective single-center analysis of cardiac patients ≤19 y treated with apixaban. Patients were evaluated for safety (clinically relevant non-major (CRNM) or major bleeding; thrombotic events) and effectiveness (thrombus improvement by imaging)...
March 13, 2023: Journal of Thrombosis and Haemostasis: JTH
Hilary Whitworth, Ernest K Amankwah, Marisol Betensky, Lana A Castellucci, Adam Cuker, Neil A Goldenberg, Christoph Male, Elliot Rinzler, Ayesha Zia, Leslie Raffini
Despite the growing number of pediatric antithrombotic clinical trials, standardized safety and efficacy outcome definitions for pediatric venous thromboembolism (VTE) clinical trials have not been updated since 2011. Many recent trials have adapted the recommended definitions, leading to heterogeneity in outcomes and limiting our ability to compare studies. The International Society on Thrombosis and Haemostasis Scientific and Standardization Subcommittee (SSC) on Pediatric and Neonatal Thrombosis and Hemostasis organized a Task Force to update the efficacy and safety outcome definitions for pediatric VTE clinical trials...
March 13, 2023: Journal of Thrombosis and Haemostasis: JTH
Ludovica Lombardi, Francesca Maiorca, Ramona Marrapodi, Annamaria Sabetta, Noemi Scafa, Davide Pallucci, Marzia Miglionico, Giulio F Romiti, Bernadette Corica, Silvia Piconese, Antonella Polimeni, Fabio Pulcinelli, Roberto Cangemi, Marcella Visentini, Stefania Basili, Lucia Stefanini
BACKGROUND: Genetic-based COVID-19 vaccines have proved highly effective in reducing the risk of hospitalization and death. As they were first distributed on a large-scale population, adenoviral-based vaccines were linked to a very rare thrombosis with thrombocytopenia syndrome and the interplay between platelets and vaccinations increasingly gained attention. OBJECTIVE: To study the crosstalk between platelets and the vaccine-induced immune response. METHODS: We prospectively enrolled young healthy volunteers who received the mRNA-based vaccine, BNT162b2 (n=15), or the adenovirus-based vaccine, AZD1222 (n=25) and studied their short-term platelet and immune response before and after vaccine injections...
March 12, 2023: Journal of Thrombosis and Haemostasis: JTH
Linlin Wang, Pengfei Wang, Fuyuan Zhang, Xiaochong Guo, Xiang Chen, Dawei Guan, Rui Zhao
No abstract text is available yet for this article.
March 11, 2023: Journal of Thrombosis and Haemostasis: JTH
Yetunde A Ayinuola, Deborah L Donahue, Jermilia Charles, Zhong Liang, Francis J Castellino, Victoria A Ploplis
BACKGROUND: Streptococcus pyogenes (GAS) is a human bacterial pathogen that generates an array of mild to very severe diseases. Worldwide there are approximately 700 million cases of GAS infection per year. In some strains of GAS, the surface-resident M-protein, Plasminogen-binding Group A Streptococcal M-Protein (PAM), binds directly to human host plasminogen (hPg) where it is activated to plasmin (hPm) through a mechanism involving Pg/bacterial streptokinase (SK) complex. Binding to Pg and its activation are dictated by selected sequences within the human host Pg protein which has made it difficult to generate animal models to study this pathogen...
March 11, 2023: Journal of Thrombosis and Haemostasis: JTH
Matteo Candeloro, Emanuele Valeriani, Manuel Monreal, Walter Ageno, Nicoletta Riva, Sam Schulman, Soo-Mee Bang, Meritxell Mellado, José Antonio Díaz-Peromingo, Jorge Moisés, Ana María Díaz-Brasero, Juan-Carlos Garcia-Pagan, Valeria Perez-Campuzano, Marco Senzolo, Andrea De Gottardi, Marcello Di Nisio
BACKGROUND: The clinical relevance and management of incidental splanchnic vein thrombosis (SVT) remain poorly defined. OBJECTIVES: To evaluate the clinical course of incidental SVT in comparison with symptomatic SVT and assess safety and effectiveness of anticoagulant treatment in incidental SVT. METHODS: Individual patient data meta-analysis of randomized controlled trials or prospective studies published up to June 2021. Efficacy outcomes were recurrent venous thromboembolism (VTE) and all-cause mortality...
March 10, 2023: Journal of Thrombosis and Haemostasis: JTH
Cecilia Becattini, Maria Cristina Vedovati
No abstract text is available yet for this article.
March 8, 2023: Journal of Thrombosis and Haemostasis: JTH
Yang Sun, Lujun Zhang, Yu Cao, Xingsheng Li, Fan Liu, Xiaoxiao Cheng, Jianlin Du, Haitao Ran, Zhigang Wang, Yongyong Li, Yuxing Feng, Liwen Liang, Wenhua Su, N D Melgiri, Hong Zhang, Rongzhong Huang
BACKGROUND: Stroke accelerates inflammatory monocyte recruitment to the endothelium and consequent atheroprogression via high-mobility group box 1-receptor for advanced glycation end products (Hmgb1-RAGE) signaling. Notably, Hmgb1 interacts with multiple Toll-like receptors (TLRs) and promotes TLR4-mediated pro-inflammatory myeloid cell activation. Therefore, TLR-associated mechanism(s) within monocytes may play a role in Hmgb1-driven post-stroke atheroprogression. OBJECTIVES: We aimed to elucidate the TLR-associated mechanism(s) within monocytes that contribute to stroke-induced exacerbation of atherosclerotic disease...
March 7, 2023: Journal of Thrombosis and Haemostasis: JTH
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