Thrombosis and haemostasis最新文献

{"title":"Factor XIII-A Transglutaminase Contributes to Neutrophil Extracellular Trap (NET)-mediated Fibrin(ogen) Network Formation and Crosslinking.","authors":"Fatemeh Soltani, Mélanie Welman, Sahar Ebrahimi Samani, Alain Pacis, Marie Lordkipanidzé, Mari T Kaartinen","doi":"10.1055/a-2504-1559","DOIUrl":"10.1055/a-2504-1559","url":null,"abstract":"<p><strong>Background: </strong> Neutrophil extracellular traps can contribute to thrombosis via stabilization of fibrin network, which is normally conducted by plasma transglutaminase, Factor XIII-A as part of coagulation cascade. The possible presence and activity of FXIII-A in neutrophils or during NETosis are unknown. Here, we investigated potential presence of FXIII-A in neutrophils and participation in NET-fibrin(ogen) interaction in vitro<i>.</i> METHODS:  Data mining of human and mouse <i>F13A1/F13a1</i> mRNA expression in whole-body scRNA sequence atlases was conducted. <i>F13a1</i> mRNA and protein expression was assessed in isolated mouse bone marrow neutrophils. NETosis was induced using 12-phorbol 13-myristate acetate (PMA), and the transglutaminase activity was assessed with 5-(biotinamido)pentylamine incorporation to plasma fibronectin and a fluorescence-fibrin(ogen)-based activity assay using ATTO488-Cadaverine. Externalization of FXIII-A and its interaction with neutrophil extracellular trap (NET) markers, namely, decondensed DNA, CitH3, and MPO, were examined with immunofluorescence microscopy. NET-fibrin(ogen) interaction was investigated with and without serum and/or transglutaminase inhibitor, NC9. Effect of soluble fibrinogen and fibrin(ogen) network on NETosis was also assessed.</p><p><strong>Results: </strong> Data mining of RNAseq atlases showed <i>F13A1/F13a1</i> expression in adipose tissue, blood, and bone marrow neutrophils. mRNA expression and protein production were confirmed in isolated neutrophils where expression was comparable to that of macrophages and monocytes. FXIII-A was externalized and active as a transglutaminase and colocalized with NET markers during NETosis. FXIII-A transglutaminase activity promoted NET-fibrin(ogen) interaction and entrapment of neutrophils within fibrin(ogen) matrix. Soluble fibrinogen or fibrin(ogen) network did not induce NETosis.</p><p><strong>Conclusion: </strong> This study identifies neutrophils as a source of FXIII-A and suggests its role in stabilizing NET-fibrin(ogen) matrix structures.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary versus Secondary Immune Thrombocytopenia (ITP): A Meeting Report from the 2023 McMaster ITP Summit.","authors":"Dimpy Modi, Saifur R Chowdhury, Syed Mahamad, Hayley Modi, Douglas B Cines, Cindy E Neunert, Hanny Al-Samkari, Nichola Cooper, Guillaume Moulis, Charlotte Cunningham-Rundles, Howard A Liebman, James B Bussel, Vicky R Breakey, Ishac Nazy, Donald M Arnold","doi":"10.1055/a-2508-1112","DOIUrl":"10.1055/a-2508-1112","url":null,"abstract":"<p><p>The McMaster Immune Thrombocytopenia (ITP) Summit, held on October 27, 2023, was an educational seminar from leading experts in immune thrombocytopenia and related disorders geared toward hematologists, internists, immunologists, and clinical and translational scientists. The focus of the Summit was to review the mechanisms, diagnosis, and treatment of primary versus secondary ITP. Specific objectives were to describe the unique features of secondary ITP, and to review its mechanisms in the context of autoimmune disease and infection. The key messages in this Summit were: (1) ITP is a heterogeneous disease, and genetic and immunologic insights may help classify patient subtypes; (2) exploring the autoimmune mechanisms and their association with hypogammaglobulinemia in patients with secondary ITP could improve our understanding of ITP and its subtypes; (3) investigating the mechanisms of ITP in the context of infections caused by viruses such as CMV, HIV, dengue, and hepatitis C, or bacteria such as <i>H. pylori</i>, or vaccinations could provide insight into the causes of ITP. A better understanding of secondary ITP could help elucidate the pathogenesis of ITP.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the Contact System and Intrinsic Pathway in Peripheral and Portal Venous Circulations in Liver Cirrhosis.","authors":"Elena Campello, Alberto Zanetto, Yuriy Prokopenko, Anton Ilich, Chatphatai Moonla, Cristiana Bulato, Serena Toffanin, Sarah Shalaby, Romilda Cardin, Giulio Barbiero, Sabrina Gavasso, Nigel S Key, Marco Senzolo, Paolo Simioni","doi":"10.1055/a-2507-2449","DOIUrl":"10.1055/a-2507-2449","url":null,"abstract":"<p><strong>Background: </strong> Portal vein system-specific risk factors contributing to portal vein thrombosis in cirrhosis are poorly investigated.</p><p><strong>Aim: </strong> This study aimed to quantify contact system and intrinsic pathway activation in the peripheral compared to portal venous blood in patients with decompensated cirrhosis.</p><p><strong>Methods: </strong> Adult patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt underwent simultaneous blood sampling from a peripheral vein and the portal vein. Complexes of serine proteases with their respective inhibitors were measured by ELISA to quantify contact system (PKa:C1-INH [plasma kallikrein:C1-esterase inhibitor] and FXIIa:C1-INH) and intrinsic pathway activation (FXIa:C1-INH, FXIa:α1at [α-1 antitrypsin], FXIa:AT [antithrombin], and FIXa:AT).</p><p><strong>Results: </strong> Twenty patients with cirrhosis (mean age 55 ± 7 years, M = 58%, Child-Pugh A/B/C 6/11/3) and 25 healthy controls (mean age 45 ± 12 years, M = 60%) were enrolled. The etiology of cirrhosis was primarily alcohol abuse, followed by chronic viral infection. Log-transformed peripheral levels of all the complexes were significantly higher in patients compared with controls. While levels of PKa:C1-INH, FXIIa:C1-INH, FXIa:C1-INH and FXIa:α1at were similar in peripheral and portal venous blood in cirrhotic patients, FXIa:AT and FIXa:AT levels were significantly higher in portal blood (<i>p</i> = 0.013 and 0.011, respectively). FXIa:C1-INH significantly correlated with both contact system complexes (FXIIa:C1-INH and PKa:C1-INH) and with FIX:AT.</p><p><strong>Conclusion: </strong> Markers of contact system and intrinsic pathway activation in the systemic circulation were significantly higher in cirrhosis versus controls. Complexes of FXIa and FIXa with AT were significantly higher in the portal than in peripheral plasma in cirrhosis, possibly indicating a unique heparin-like effect in portal venous blood.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brisk Walking Pace Offsets Venous Thromboembolism Risk Equivalent to Established Monogenic Mutations.","authors":"Wenyan Xian, Yifan Tao, Chong You, Ruinan Sun, Janice M Ranson, Valerio Napolioni, Patrick W C Lau, Jie Huang","doi":"10.1055/a-2461-3349","DOIUrl":"10.1055/a-2461-3349","url":null,"abstract":"<p><strong>Background: </strong> Mendelian mutations in the Prothrombin gene (<i>F2</i>) and the factor V Leiden gene (<i>F5</i>) genes are established risk factors for venous thromboembolism (VTE). Walking pace is associated with the risk of coronary artery diseases, but no study has investigated its association with VTE. This study aimed to investigate the association and causality between walking pace and VTE, compare its population risk with established Mendelian mutations, and determine if blood biomarkers mediate its effect.</p><p><strong>Methods: </strong> We followed up 445,261 UK Biobank participants free of VTE at baseline. Self-reported walking pace was collected via touchscreen questionnaire at baseline. The carrier status of two Mendelian mutations in <i>F2</i> and <i>F5</i> genes was determined by the genotypes of rs1799963 (G20210A, c.*97 G > A) and rs6025 (p.R534Q), respectively. Cox proportional hazard model was used to estimate the effect of walking pace on incident VTE. We conducted a bidirectional Mendelian randomization (MR) analysis, by using 70 single-nucleotide polymorphisms (SNPs) from a walking pace genome-wide association studies (GWAS) and 93 SNPs from a VTE GWAS as instrumental variables. We used both individual-level data and GWAS summary statistics for mediation analysis.</p><p><strong>Results: </strong> Over a median follow-up period of 12.8 years, 11,155 incident VTE cases were identified. The 10-year incidence rates for brisk and slow walking pace were 1.32% (confidence interval [CI]: 1.27-1.37%) and 3.90% (CI: 3.71-4.09%), respectively. For noncarriers, <i>F2</i> and <i>F5</i> carriers, the 10-year incidence rates were 1.70% (CI: 1.66-1.73%), 2.94% (CI: 2.66-3.22%), and 3.62% (CI: 3.39-3.84%), respectively. The overall risk of VTE for <i>F5</i> mutation carriers with a brisk walking pace (2.65%) was smaller than that for noncarriers with a slow walking pace (3.66%). For <i>F5</i> mutation carriers, brisk pace (but not steady pace) reduces the risk of VTE (<i>p</i> interaction < 0.05). MR analyses displayed a causal relationship (inverse variance weighted: <i>p</i> = 3.21 × 10^-5) from walking pace to VTE incidence. Mediation analysis showed that serum albumin (ALB) and cystatin C (CYS) levels partially mediated the effect of brisk walking pace on the risk of VTE incidence, with mediation proportions of 8.7 to 11.7%, respectively.</p><p><strong>Conclusion: </strong> On the population scale, the protective effect of brisk walking pace offsets the risk of VTE caused by Mendelian mutations. We provided preliminary evidence that a brisk walking pace causally reduces the risk of VTE. Serum ALB and CYS partially mediate this effect.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Venous Thromboembolism with Edoxaban over 18 Months: Results from ETNA-VTE Europe.","authors":"Giancarlo Agnelli, Ulrich Hoffmann, Philippe Hainaut, Sean Gaine, Cihan Ay, Michiel Coppens, Marc Schindewolf, David Jimenez, Eva-Maria Fronk, José Souza, Petra Laeis, Peter Bramlage, Bernd Brüggenjürgen, Pierre Levy, Alexander T Cohen","doi":"10.1055/a-2497-4089","DOIUrl":"https://doi.org/10.1055/a-2497-4089","url":null,"abstract":"<p><strong>Background: </strong> The benefits and risks of extending anticoagulant treatment beyond the first 3 to 6 months in patients with venous thromboembolism (VTE) in clinical practice are not well understood.</p><p><strong>Methods: </strong> ETNA-VTE Europe is a prospective, noninterventional, post-authorization study in unselected patients with VTE treated with edoxaban in eight European countries for up to 18 months. Recurrent VTE, major bleeding, and all-cause death were the primary study outcomes.</p><p><strong>Results: </strong> The median age of the 2,644 patients was 65 years; 46.6% were female, and 22.8% had a history of VTE. The median treatment duration was 50.6 weeks (interquartile range: 23.4-77.7). VTE recurrence occurred in 100 patients (3.8% at an annual rate of 2.7%/year); 37 patients (1.4%) were on edoxaban at the time of the event, with a corresponding annualized rate of 1.6%/year. Major bleeding was experienced by 37 patients (1.4%) during edoxaban treatment, corresponding to an annualized rate of 1.5%/year. Overall, 95 patients died (3.6%; annualized rate 2.6%/year), with the majority for reasons other than VTE- and cardiovascular (CV)-related causes. Out of 15 deaths (1.9%; annualized rate 2.1%/year) that occurred during edoxaban treatment, 1 was related to VTE and 11 related to CV (annualized rate 0.0%/year and 0.5%/year).</p><p><strong>Conclusions: </strong> ETNA-VTE Europe provides evidence for the real-world effectiveness of edoxaban treatment (up to 18 months) based on a low rate of VTE recurrence, all-cause death, and major bleeding, and is aligned with the results of the randomized clinical trial reassuring the use of edoxaban in the treatment of VTE in routine clinical practice.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Middle-throughput LC-MS-based platelet proteomics with minute sample amounts using semi-automated positive pressure FASP in 384-well format (PF384).","authors":"Stefan Loroch, Eleftherios Panagiotidis, Kristoffer Klewe, Frauke Swieringa, Johan Wm Heemskerk, Jan-Paul Lerch, Andreas Greinacher, Ulrich Walter, Kerstin Jurk, Tobias John, Katalin Barkovits, Thomas Dandekar, Katrin Marcus, Johannes Balkenhol","doi":"10.1055/a-2516-1812","DOIUrl":"https://doi.org/10.1055/a-2516-1812","url":null,"abstract":"<p><p>Comprehensive characterization of platelets requires various functional assays and analysis techniques, including omics-disciplines, each requiring an individual aliquot of a given sample. Consequently, the sample material per assay is often highly limited rendering downscaling a prerequisite for effective sample exploitation. Here we present a transfer of our recently introduced 96-well-based proteomics workflow (PF96) into the 384-well format (PF384) allowing for a significant increase in sensitivity when processing minute platelet protein amounts. In addition, the 4-fold higher throughput (1500 samples per lab worker per week) allows to easily meet the throughput capacities of modern LC-MS instruments. We determined optimal sample loads followed by highlighting the strengths in comparison to our previous sample preparation approach by processing only 3 µg of purified platelet protein from 22 healthy donors. Major advantages are: (I) improved identification and analyte recovery, especially of low copy number proteins, with signal intensity gains of +130 % and +107 % (peptide and protein level, respectively) (II) substantial intensity gains for key-players in platelet activation including the membrane receptors PAR4, P2X1, GPVI, GPV, GPIX and the downstream mediators AKT, PKA, Rap1, Lyn (III) improved reproducibility with a reduction of technical variance from 22 / 25 % down to 16 / 19 % for detection of lower / higher abundant disease markers and (IV) a 4-fold increase in sample preparation throughput. Taken together, these advantages render PF384 a promising future in clinical proteomics and might pave the way of platelet proteomics with minute sample amounts into molecular diagnostics.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial Damage in JAK2V617F Myeloproliferative Neoplasms with Splanchnic Vein Thrombosis.","authors":"Blanca De Moner, Julia Martinez-Sanchez, Marta Garrote, Alex Ramos, Helena Ventosa-Capell, Ana Moreno-Castaño, Meritxell Nomdedeu, Asunción Ojeda, Gines Escolar, Joan Carles Garcia-Pagan, Eduardo Arellano-Rodrigo, Enric Carreras, Alberto Alvarez-Larran, Maribel Díaz-Ricart","doi":"10.1055/a-2498-4849","DOIUrl":"https://doi.org/10.1055/a-2498-4849","url":null,"abstract":"<p><strong>Background: </strong> <i>JAK2</i>V617F-mutated myeloproliferative neoplasms (MPN) exhibit abnormal proliferation of bone marrow progenitors and increased risk of thrombosis, specifically in splanchnic veins (SVT). The contribution of the endothelium to the development of the prothrombotic phenotype was explored.</p><p><strong>Material and methods: </strong> Plasma and serum samples from <i>JAK2</i>V617F MPN patients with (n=26) or without (n=7) thrombotic debut and different treatments, were obtained (n=33). Cultured endothelial cells (ECs) were exposed to serum samples from these patients and from healthy donors as controls. Changes in markers of inflammation (VCAM-1, ICAM-1), cell permeability (VE-cadherin), production of VWF, extracellular matrix (ECM) reactivity, and activation of intracellular signaling pathways related to stress, proliferation, inflammation (Akt, p44/42, IkBa), and JAK2/STAT3 pathway, were assessed by immunofluorescence, flow adhesion, SDS-PAGE and immunoblot. Additionally, circulating markers of endothelial activation and damage (VWF, sVCAM-1, sTNFRI, thrombomodulin, angiopoietin-2, a2-antiplasmin activity, PAI-1) were evaluated in Patients' plasma.</p><p><strong>Results: </strong> The in vitro studies showed that EC exposure to MPN thrombotic patients' sera resulted in increased VCAM-1 and ICAM-1, and reduced VE-cadherin expression (p<0.05) at the cell surface. Production and release of VWF to the ECM were higher (p<0.05), with increased platelet adhesion after perfusing whole blood, being more noticeable in response to sera from non-treated patients. Furthermore, intracellular activation of Akt, p44/42, IkBa and JAK2/STAT3 was observed. Moreover, plasma levels of VWF, TNF-R1, VCAM-1, thrombomodulin, and angiopoietin-2 were higher in <i>JAK2</i>V617F+ MPN patients with thrombosis.</p><p><strong>Conclusion: </strong> The present findings suggest that circulating factors in MPNs with SVT debut induce endothelial proinflammatory and prothrombotic phenotypes, which are modulated <i>in vitro</i> with MPN treatment.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-Time Imaging of Platelet-Initiated Plasma Clot Formation and Lysis Unveils Distinct Impacts of Anticoagulants.","authors":"Yuko Suzuki, Nitty S Mathews, Hideto Sano, Nanami Morooka, Naoki Honkura, Tetsumei Urano","doi":"10.1055/a-2497-4213","DOIUrl":"https://doi.org/10.1055/a-2497-4213","url":null,"abstract":"<p><strong>Background: </strong> Fibrinolysis is spatiotemporally well-regulated and greatly influenced by activated platelets and coagulation activity. Our previous real-time imaging analyses revealed that clotting commences on activated platelet surfaces, resulting in uneven-density fibrin structures, and that fibrinolysis initiates in dense fibrin regions and extends to the periphery. Despite the widespread clinical use of direct oral anticoagulants (DOACs), their impact on thrombin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) and fibrinolysis remains unclear. Here, we investigated the effects of different DOACs on the TAFI-mediated inhibition of fibrinolysis.</p><p><strong>Methods: </strong> Using human platelet-containing plasma, we performed turbidimetric assays, thrombin generation assays, and confocal laser scanning microscopy to assess the effects of anticoagulants on fibrinolysis.</p><p><strong>Results and conclusion: </strong> Activated platelets-prolonged plasma clot lysis time, shortened by activated TAFI inhibitor (TAFIaI), positively correlated with the amount of thrombin generated. Rivaroxaban (an activated factor X inhibitor) and dabigatran (a direct thrombin inhibitor) dose-dependently shortened lysis time comparably. The highest concentration of DOACs showed no further shortening of lysis time with TAFIaI. The fibrin network structures initiated by activated platelets and the localization of fluorescently labeled plasminogen were unique for these two drugs. Rivaroxaban maintained an uneven fibrin network but promoted faster plasminogen accumulation and fibrinolysis from outside dense fibrin regions. Conversely, dabigatran resulted in a more even fibrin network, with fibrinolysis starting from the activated platelets and propagating to the periphery. Visualizing and analyzing the patterns of fibrin network formation, plasminogen accumulation, and fibrinolysis provide new insights into the specific impact of anticoagulants on coagulation and fibrinolysis.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Socioeconomic Burden of Pulmonary Embolism in Europe: Shifting Priorities and Challenges for Novel Reperfusion Strategies.","authors":"Katharina Mohr, Stefano Barco, Thomas Neusius, Stavros Konstantinides","doi":"10.1055/a-2505-8711","DOIUrl":"10.1055/a-2505-8711","url":null,"abstract":"<p><p>In-hospital case fatality related to acute pulmonary embolism (PE) has been falling since the beginning of this century. However, annual incidence rates continue to climb, and an increasing number of PE survivors need long-term follow-up, chronic anticoagulation treatment, and readmission(s) to the hospital. In European countries, median reimbursed hospital costs for acute PE are still moderate compared with the United States but can increase several-fold in patients with comorbidities and those necessitating potentially life-saving reperfusion treatment. The use of catheter-directed treatment (CDT) has constantly increased in the United States since the past decade, and it has now entered a rapid growth phase in Europe as well, estimated to reach an annual penetration rate of up to 31% among patients with intermediate-high- or high-risk PE by 2030. Ongoing randomised controlled trials are currently investigating the clinical efficacy and safety of these devices. In addition, they will deliver data permitting calculation of their cost-effectiveness in different health care reimbursement systems, by revealing the extent to which they can reduce complications and consequently the need for intensive care and the overall length of hospital stay. After discharge, key cost drivers are related to chronic cardiopulmonary diseases (other than PE itself) leading to frequent readmissions, persistent symptoms, and functional limitations which result in poor quality of life, productivity loss, and substantial indirect costs. Implementation of structured outpatient programmes with a holistic approach to post-PE care, targeting overall cardiovascular health and the patient's well-being, bears the potential to cost-effectively reduce the overall socioeconomic burden of PE.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Clot Waveform Analysis Parameters and the Severity of Liver Cirrhosis.","authors":"Kessarin Thanapirom, Sirinporn Suksawatamnuay, Panarat Thaimai, Prooksa Ananchuensook, Pitiphong Kijrattanakul, Pantep Angchaisuksiri, Pisit Tangkijvanich, Sombat Treeprasertsuk, Piyawat Komolmit","doi":"10.1055/a-2505-8616","DOIUrl":"https://doi.org/10.1055/a-2505-8616","url":null,"abstract":"<p><strong>Background: </strong> Clot waveform analysis (CWA) provides a global assessment of hemostasis and may be useful for patients with cirrhosis with complex hemostatic abnormalities. This study aimed to assess the association between prothrombin time (PT-) and activated partial thromboplastin time (aPTT-) based CWA parameters and cirrhosis severity and prospectively evaluate the role of CWA in predicting mortality and acute decompensation (AD) over 1 year.</p><p><strong>Methods: </strong> This prospective study included adult patients with cirrhosis between June 2021 and December 2023 at Chulalongkorn University Hospital. The PT- and aPTT-based CWA parameters were obtained using an automated coagulation analyzer.</p><p><strong>Results: </strong> A total of 560 patients with cirrhosis were included; 165 (29.5%) and 47 (11.5%) had Child-Turcotte-Pugh (CTP) B and C cirrhosis, respectively. The PT- and aPTT-based CWA parameters, including maximum velocity (min1), maximum acceleration (min2), and maximum deceleration (max2), were significantly lower (<i>p</i> ≤ 0.05) in patients with decompensated cirrhosis than in those with compensated cirrhosis. Additionally, CWA values were significantly higher in patients with higher CTP and Model for End-Stage Liver Disease (MELD) scores. Multivariable analysis revealed that liver stiffness (LS) and max2 of PT-based CWA assay were independently associated with CTP B/C. In addition, min2 and max2 of PT-based CWA assay were independently associated with 1-year mortality. No significant differences in CWA parameters were observed between patients with and without portal vein thrombosis. CWA parameters were not related to AD during the 1-year follow-up.</p><p><strong>Conclusion: </strong> A hypocoagulable profile based on CWA parameters is associated with advanced-stage cirrhosis. CWA may be a useful objective marker for assessing cirrhosis severity and predicting 1-year mortality.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}