Journals Journal of Thrombosis and Haem...

Journal of Thrombosis and Haemostasis : JTH
Francesca Ferraresso, Jerry Leung, Christian J Kastrup
Regulation of fibrinolysis, the process that degrades blood clots, is pivotal in maintaining haemostasis. Dysregulation leads to thrombosis or excessive bleeding. Proteins in the fibrinolysis system include fibrinogen, coagulation factor XIII, plasminogen, tissue plasminogen activator (tPA), urokinase (uPA), α2-antiplasmin, thrombin-activatable fibrinolysis inhibitor (TAFI), plasminogen activator inhibitor-1 (PAI-1), α2-macroglobulin, and others. While each of these is a potential therapeutic target for diseases, they each lack effective or long-acting inhibitors...
April 23, 2024: Journal of Thrombosis and Haemostasis: JTH
Meghan E McGrady, Vera Ignjatovic, Sophie Jones, Aisha Bruce, Neil A Goldenberg, Mattia Rizzi, Courtney D Thornburg, Kevin E Todd, Lori Luchtman-Jones
In response to growing recognition that non-adherence prevents children, adolescents, and young adults from achieving the therapeutic benefits of anticoagulant medication, the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis convened a working party on medication adherence. The primary aim of this manuscript was to synthesize recommendations from the larger adherence science literature to provide guidance regarding the classification, collection, and interpretation of anticoagulation adherence data...
April 18, 2024: Journal of Thrombosis and Haemostasis: JTH
Bethany T Samuelson Bannow
Bleeding is a well-recognized side effect of anticoagulant therapy, which is used to treat venous thromboembolism (VTE) in individuals of all ages, including those of female sex, who commonly experience VTE as a complication of hormonal therapies and/or pregnancy. Heavy menstrual bleeding (HMB) is also extremely common in reproductive aged individuals of female sex. Despite these overlapping situations, relatively little attention has been paid to the impact of anticoagulant-associated HMB on treatment strategies and the patient experience...
April 18, 2024: Journal of Thrombosis and Haemostasis: JTH
Soroush Shahryari Fard, Theodore J Perkins, Philip S Wells
BACKGROUND: Thus far, all the clinical models developed to predict major bleeding in patients on extended anticoagulation therapy use the baseline predictors to stratify patients into different risk groups. Therefore, these models do not account for the clinical changes and events that occur after the baseline visit, which can modify risk of bleeding. However, it is difficult to develop predictive models from the routine follow-up clinical interviews which are irregular sequences of multivariate time series data...
April 18, 2024: Journal of Thrombosis and Haemostasis: JTH
David-Alexandre Trégouët, Pierre-Emmanuel Morange
This invited review follows the oral presentation "To Sequence or Not to Sequence, That Is Not the Question; But 'When, Who, Which and What For?' Is" given during the State of the Art session "Translational Genomics in Thrombosis: From OMICs to Clinics" of the International Society on Thrombosis and Haemostasis 2023 Congress. Emphasizing the power of next-generation sequencing technologies and the diverse strategies associated with DNA variant analysis, this review highlights the unresolved questions and challenges in their implementation both for the clinical diagnosis of venous thromboembolism and in translational research...
April 18, 2024: Journal of Thrombosis and Haemostasis: JTH
Bella Madan, Margareth C Ozelo, Priyanka Raheja, Emily Symington, Doris V Quon, Andrew D Leavitt, Steven W Pipe, Gillian Lowe, Gili Kenet, Mark T Reding, Jane Mason, Michael Wang, Annette von Drygalski, Robert Klamroth, Susan Shapiro, Hervé Chambost, Amy L Dunn, Johannes Oldenburg, Sheng-Chieh Chou, Flora Peyvandi, Carolyn M Millar, Dane Osmond, Hua Yu, Ebony Dashiell-Aje, Tara M Robinson, Johnny Mahlangu
BACKGROUND: Valoctocogene roxaparvovec transfers a human factor VIII (FVIII) coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection. OBJECTIVE: Present 3-year efficacy and safety in the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial. METHODS: GENEr8-1 enrolled 134 adult males with severe hemophilia A who were receiving FVIII prophylaxis. Efficacy endpoints included annualized bleeding rate (ABR), annualized FVIII utilization (AFU), FVIII activity (chromogenic substrate assay; imputed as 1 IU/dL at baseline and 0 IU/dL after discontinuation), and the Haemophilia-Specific Quality of Life Questionnaire for Adults (Haemo-QOL-A)...
April 11, 2024: Journal of Thrombosis and Haemostasis: JTH
Ahmed Hjazi, Celia Gonzalez Maroto, Michael Appiah, Maria Elena Rodriguez-Gutierrez, Ana Ignat, Golzar Mobayen, Theresa Page, Thomas A J McKinnon
BACKGROUND: Carfilzomib (CFZ) is a second-generation proteasome inhibitor used to treat multiple myeloma. Potent inhibition of the proteasome results in chronic proteotoxic endoplasmic reticulum (ER) stress, leading to apoptosis. While CFZ has improved survival rates in multiple myeloma, it is associated with an increased risk of cardiovascular adverse effects. While this has been putatively linked to cardiotoxicity, CFZ could potentially also exhibit adverse effects on the endothelium...
April 10, 2024: Journal of Thrombosis and Haemostasis: JTH
Laurie Josset, Alexandre Leuci, Maissaa Janbain, Anaëlle De-Wreede, Stephanie Desage, Anne Lienhart, Valérie Bin, Dorothée Lambert, Xavier Delavenne, Yesim Dargaud
BACKGROUND: Emicizumab has been approved for the prophylaxis of patients with hemophilia A with or without inhibitors. However, spontaneous and trauma-induced breakthrough bleeds have been reported in patients on emicizumab prophylaxis, and no laboratory assay has been validated to evaluate the hemostatic activity of emicizumab. OBJECTIVES: The thrombin generation assay (TGA) could be a surrogate marker of the hemostatic efficacy of emicizumab. The correlation between TGA and the methods used to measure emicizumab blood concentration was evaluated in this study...
April 6, 2024: Journal of Thrombosis and Haemostasis: JTH
Nicola Potere, Isabelle Mahé, Pantep Angchaisuksiri, Gabriela Cesarman-Maus, Chee Wee Tan, Anila Rashid, Farjah H AlGahtani, Egidio Imbalzano, Nick van Es, Avi Leader, Edeghonghon Olayemi, Ettore Porreca, Fionnuala Ní Áinle, Helen C Okoye, Matteo Candeloro, Didier Mayeur, Luca Valerio, R Cary Clark, Lana A Castellucci, Stefano Barco, Marcello Di Nisio
BACKGROUND: Venous thromboembolism (VTE) is a major preventable cause of morbidity, disability, and mortality in subjects with cancer. A global appraisal of cancer-associated VTE education and awareness is not available. OBJECTIVES: To evaluate VTE-related education, awareness, and unmet needs from the perspective of people living with cancer using a quantitative and qualitative approach. PATIENTS/METHODS: This cross-sectional study used data from an online-based survey covering multidimensional domains of cancer-associated VTE...
April 4, 2024: Journal of Thrombosis and Haemostasis: JTH
Stella Bijkerk, Harm J Lourens, Wout G N Mares, Corine A van Kampen, Maurits J van der Veen, Henk J Adriaansen, Erik D Ponfoort, Barbara Festen, G Wouter Westendorp, Jörgen M P Rovers, Gerie M C Groot, Hans-Peter R Bootsma, Linde M Amelung, Sander Bins, Gerjo Velders, Remy H H Bemelmans
BACKGROUND: The effect of the vitamin K antagonist (VKA) acenocoumarol on coagulation needs to be reversed when patients undergo an invasive procedure with considerable bleeding risk. A strategy to achieve this is administering oral vitamin K before a procedure while continuing acenocoumarol. OBJECTIVES: To assess the effect on periprocedural International Normalized Ratio (INR)-values and safety using oral vitamin K as anticoagulant reversal method. METHODS: In this prospective cohort study, consecutive patients using acenocoumarol undergoing elective procedures between 2019 and 2022 were included...
April 3, 2024: Journal of Thrombosis and Haemostasis: JTH
Poorva Bindal, Rushad Patell, Thita Chiasakul, Mandy N Lauw, Amica Ko, Tzu-Fei Wang, Jeffrey I Zwicker
BACKGROUND: Chimeric antigen receptor T cell (CAR T-cell) therapy is increasingly utilized for treatment of hematologic malignancies. Hematologic toxicities including thrombosis and bleeding complications have been reported. Accurate estimates for thrombotic and bleeding outcomes are lacking. METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to February 2022 for studies reporting thrombotic or bleeding outcomes in patients receiving CAR T-cell therapy...
April 2, 2024: Journal of Thrombosis and Haemostasis: JTH
Yohei Hisada, Sierra J Archibald, Karan Bansal, Yanjun Chen, Chen Dai, Sindhu Dwarampudi, Nora Balas, Lindsey Hageman, Nigel S Key, Smita Bhatia, Ravi Bhatia, Nigel Mackman, Radhika Gangaraju
BACKGROUND: Coagulopathy and associated bleeding and deep vein thrombosis (DVT) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated. OBJECTIVES: To evaluate the associations between biomarker levels and bleeding and DVT in acute leukemia patients. PATIENTS/METHOD: We examined plasma levels of activators, inhibitors and biomarkers of the coagulation and fibrinolytic pathways in patients ≥18 years with newly diagnosed acute leukemia compared to normal controls...
April 2, 2024: Journal of Thrombosis and Haemostasis: JTH
Sebastiaan N J Laan, Suzan de Boer, Richard J Dirven, Iris van Moort, Thomas B Kuipers, Hailiang Mei, Ruben Bierings, Jeroen Eikenboom
BACKGROUND: Endothelial colony forming cells (ECFCs) derived from patients can be used to investigate pathogenic mechanisms of vascular diseases like Von Willebrand Disease. Considerable phenotypic heterogeneity has been observed between ECFC clones derived from healthy donors. This heterogeneity needs to be well understood in order to use ECFCs as endothelial models for disease. Therefore, we aim to determine phenotypic and gene expression differences between control ECFCs. METHODS: A total of 34 ECFC clones derived from 16 healthy controls were analyzed...
April 2, 2024: Journal of Thrombosis and Haemostasis: JTH
Yuanbin Chen, Wei Jiao, Yonghua Wang, Zhijuan Liang, Liping Wang, Dan Li, Ye Liang, Haitao Niu
BACKGROUND: Patients with cancer are at an increased risk of developing a hypercoagulative phenotype and venous thromboembolism. However, no clinical trial has yet confirmed that anticoagulant therapy improves cancer prognosis, and the mechanism underlying hypercoagulation in patients with bladder cancer is not well understood. OBJECTIVES: We hypothesized that the prognostic genes affect tumor progression via tumor-mediated coagulation. METHODS: We detected the most significant prognostic genes of bladder cancer with The Cancer Genome Atlas dataset, and validated them in two Gene Expression Omnibus and one ArrayExpress datasets...
March 28, 2024: Journal of Thrombosis and Haemostasis: JTH
Quintijn Bonnez, Charlotte Dekimpe, Tim Bekaert, Edwige Tellier, Gilles Kaplanski, Bérangère S Joly, Agnès Veyradier, Paul Coppo, Jeroen Lammertyn, Claudia Tersteeg, Simon F De Meyer, Karen Vanhoorelbeke
BACKGROUND: Laboratory diagnosis of immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains challenging when ADAMTS13 activity ranges between 10-20%. To prevent misdiagnosis, open ADAMTS13 conformation gained clinical attention as a novel biomarker especially to diagnose acute iTTP in patient with diagnostic undecisive ADAMTS13 activity. Plasma ADAMTS13 conformation analysis corrects for ADAMTS13 antigen with both parameters being characterized in enzyme-linked immunosorbent assay (ELISA)-based reference assays requiring expert technicians...
March 28, 2024: Journal of Thrombosis and Haemostasis: JTH
Barret Rush, Jennifer Ziegler, Stephanie Dyck, Surinder Dhaliwal, Owen Mooney, Sylvain Lother, Leo Anthony Celi, Asher A Mendelson
BACKGROUND: Interventional therapies (ITs) are an emerging treatment modality for pulmonary embolism (PE); however, the degree of racial, sex-based, and sociodemographic disparities in access and timing is unknown. OBJECTIVES: To investigate barriers to access and timing of ITs for PE across the United States. METHODS: A retrospective cohort study utilizing the Nationwide Inpatient Sample from 2016-2020 included adult patients with PE. The use of ITs (mechanical thrombectomy and catheter-directed thrombolysis) was identified via International Classification of Diseases 10th revision codes...
March 28, 2024: Journal of Thrombosis and Haemostasis: JTH
Judith P L Verlaan, Bernadine H Stegeman, Jasmijn F Timp, Luuk J J Scheres, Linda E Flinterman, Frans M Helmerhorst, Frits R Rosendaal, Suzanne C Cannegieter, Astrid van Hylckama Vlieg
BACKGROUND: Extensive evidence is available on hormonal contraceptive (HC) use and the risk of a first venous thromboembolism (VTE) event. Despite recommendations to discontinue combined HC (CHC) use, some women continue or start its use after a first VTE. OBJECTIVES: We aimed to evaluate the VTE recurrence risk associated with HC use in premenopausal women. METHODS: Premenopausal women with a first VTE included in the Multiple Environmental and Genetic Assessment of Venous Thrombosis study between 1999 and 2004 were followed for a recurrence until 2010...
March 28, 2024: Journal of Thrombosis and Haemostasis: JTH
Lei Chen, Jingkun Liu, Kunying Chen, Yanxun Su, Yihe Chen, Ying Lei, Jia Si, Jie Zhang, Zhaojun Zhang, Weiguo Zou, Xiaohui Zhang, Matthew T Rondina, Qian-Fei Wang, Yueying Li
BACKGROUND: Megakaryocytes (MKs) are polyploid cells responsible for producing ∼1011 platelets daily in humans. Unraveling the mechanisms regulating megakaryopoiesis holds the promise for the production of clinical-grade platelets from stem cells, overcoming significant current limitations in platelet transfusion medicine. Previous work identified that loss of the epigenetic regulator SETD2 was associated with an increased platelet count in mice. However, the role of SETD2 in megakaryopoiesis remains unknown...
March 25, 2024: Journal of Thrombosis and Haemostasis: JTH
Robert D McBane, Charles L Loprinzi, Tyler Zemla, Alfonso Tafur, Kristen Sanfilippo, Jane Jijun Liu, David A Garcia, James Heun, Krishna Gundabolu, Adedayo A Onitilo, Usha Perepu, Monic R Drescher, Stanislav Henkin, Damon Houghton, Aneel Ashrani, Henny Billett, Shaylene A McCue, Minji K Lee, Jennifer G Le-Rademacher, Waldemar E Wysokinski
BACKGROUND: Cancer-associated venous thromboembolism (VTE) management guideline recommendations include continued therapeutic anticoagulation while active cancer persists. The Federal Drug Administration label for apixaban for secondary VTE prevention includes a dose reduction to 2.5 mg twice daily after 6 months of treatment. OBJECTIVES: The study's purpose was to determine whether this dose reduction is advisable for cancer-associated VTE. METHODS: A randomized, double-blind trial compared apixaban 2...
March 25, 2024: Journal of Thrombosis and Haemostasis: JTH
Matt J Owen, Joy R Wright, Edward G D Tuddenham, John R King, Alison H Goodall, Joanne L Dunster
BACKGROUND: Mathematical models of coagulation have been developed to mirror thrombin generation in plasma, with the aim of investigating how variation in coagulation factor levels regulate haemostasis. However, current models vary in the reactions they capture, in reaction rates used, and their validation is restricted by a lack of large coherent datasets, resulting in questioning of their utility. OBJECTIVES AND METHODS: To address this debate, we systematically assessed current models against a large dataset, using plasma coagulation factor levels from 348 individuals with normal haemostasis as inputs, and compared model predictions with measured thrombin generation...
March 21, 2024: Journal of Thrombosis and Haemostasis: JTH
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