Thrombosis and haemostasis最新文献

{"title":"Characteristics of Bleeding Complications in Patients with Severe COVID-19 Requiring Veno-venous Extracorporeal Membrane Oxygenation in Japan.","authors":"Hayato Taniguchi, Takeru Abe, Ichiro Takeuchi, Shinichiro Ohshimo, Nobuaki Shime, Shigeki Kushimoto, Satoru Hashimoto, Shinhiro Takeda","doi":"10.1055/a-2411-1000","DOIUrl":"10.1055/a-2411-1000","url":null,"abstract":"<p><p>Complications during veno-venous extracorporeal membrane oxygenation (VV-ECMO) are associated with in-hospital mortality. Asian patients on extracorporeal membrane oxygenation (ECMO) have higher risks of bleeding and in-hospital mortality than Caucasian patients. This study aimed to characterize and identify bleeding complications and their associated factors related to in-hospital mortality in patients with severe coronavirus disease 2019 (COVID-19) requiring VV-ECMO in Japan.In this retrospective observational analysis, the prospective nationwide multicenter registry was used to track real-time information from intensive care units throughout Japan during the COVID-19 pandemic. VV-ECMO patients' registry data between February 1, 2020 and October 31, 2022 were used.This study included 441 patients; 178 (40%) had bleeding complications in the following sites: 20% at the cannulation site, 16% in the gastrointestinal tract, 16% in the ear-nose-throat, 13% at the tracheostomy site, 9% intrathoracic, 6% intracranial, and 5% in the iliopsoas. Anticoagulation was discontinued in >50% of patients with intracranial, iliopsoas, and gastrointestinal tract bleeding. ECMO was discontinued in one-third of patients with intracranial, intramuscular, and iliopsoas hemorrhages. Multivariable logistic regression analysis revealed that only gastrointestinal tract bleeding was associated with in-hospital mortality (odds ratio: 2.49; 95% confidence interval: 1.11-5.60; <i>p</i> = 0.03).Incidence of bleeding complications was 40% in the Japanese population. Gastrointestinal tract bleeding emerged as a significant predictor of adverse outcomes, necessitating further research into preventive strategies and optimized care protocols. These findings can guide the management of VV-ECMO patients with COVID-19.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"308-316"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Efficacy and Safety of DOACs in Inherited Antithrombin Deficiency: A Cohort Study from a Tertiary Referral Center.","authors":"Caroline Dix, Andrew J Doyle, Karen Breen, Beverley J Hunt","doi":"10.1055/a-2379-7288","DOIUrl":"10.1055/a-2379-7288","url":null,"abstract":"<p><p>Individuals with inherited antithrombin deficiency (IATD) have a high risk of venous thromboembolism (VTE). Most VTEs are managed with direct oral anticoagulants (DOACs), but the utility of DOACs in antithrombin deficiency (ATD) is unreported.Patients with IATD treated with DOAC were identified from our institutions' IATD registry. We assessed patients' characteristics, ATD type, and initial VTE characteristics, thrombosis recurrence and bleeding rates.Thirty-three patients received DOACs for 73 (38.5-111.5) months (median (interquartile range)). Prior to taking DOACs, 12 (36%) patients had VTE recurrence: these occurred after anticoagulation was ceased (4), nonadherence to VKA prior to DOAC use (3), or during heparin use in pregnancy (5). There were no VTE recurrences on standard-dose DOAC, except in a noncompliant patient receiving dabigatran. There was one recurrence with compliant DOAC use-a patient receiving rivaroxaban 10 mg. Six (18%) patients experienced clinically relevant bleeding, which was predominantly menorrhagia (5/6). One major bleeding event, intracranial hemorrhage, occurred in a patient receiving full-dose rivaroxaban who had refractory hypertension (0.5 events/100 patient-years). In this cohort, compliant DOAC users had an overall VTE recurrence rate of 0.5/100 patient-years, whereas with low-dose DOACs the event rate was 3.5/100 patient-years.Standard-dose DOACs appear efficacious and relatively safe in IATD.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"379-384"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894372","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":"Unravelling the Causal Relationship between Endometriosis and the Risk for Developing Venous Thromboembolism: A Pooled Analysis.","authors":"Pauline De Corte, Igor Milhoranca, Sylvia Mechsner, Anna Sara Oberg, Tobias Kurth, Klaas Heinemann","doi":"10.1055/a-2407-9498","DOIUrl":"10.1055/a-2407-9498","url":null,"abstract":"<p><p>To investigate the effect of endometriosis on venous thromboembolism (VTE) in oral contraceptive (OC) users. Pooled analysis on a harmonized dataset compromising international patient-centric cohort studies: INAS-VIPOS, INAS-SCORE, and INAS-FOCUS. Eleven European countries, the United States, and Canada. Individuals being newly prescribed an OC with or without an endometriosis and no VTE history.Detailed information was captured using self-administered questionnaires at baseline and every 6 to 12 months thereafter. Self-reported VTEs were medically validated and reviewed by an independent adjudication committee. Incidence rates (IRs) were calculated per 10,000 woman-years. The association of endometriosis on VTE was determined in a time-to-event analysis, calculating crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) using stabilized inverse probability of treatment weighting (IPTW).A total of 22,072 women had an endometriosis diagnosis, and 91,056 women did not. Women with endometriosis contributed 78,751 woman-years during which 41 VTE events occurred (IR: 5.2/10,000, 95% CI: 3.7-7.1) compared to 127 VTEs during 310,501 woman-years in women without endometriosis (IR: 4.1/10,000, 95% CI: 3.4-4.9). The hazard ratio of VTE in women with endometriosis was 1.79 (95% CI: 1.24-2.57) using stabilized IPTW controlling for age, body mass index, smoking, education, age at menarche, and family history of VTE. Subgroup and sensitivity analyses showed similar results.These results highlight the importance of considering endometriosis as a potential factor contributing to VTE in women using OC; however, further research on the relationship between endometriosis and VTE is warranted.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"385-394"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Hidden Culprit: Troubles with Enhanced Deglycosylation in Mechanical Circulatory Support.","authors":"Attila Braun, Elmina Mammadova-Bach","doi":"10.1055/a-2448-2989","DOIUrl":"10.1055/a-2448-2989","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"337-339"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508514","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":"Time Trends and Excess Mortality Compared to Population Controls after a First-Time Pulmonary Embolism or Deep Vein Thrombosis.","authors":"Katarina Glise Sandblad, Carl Johan Svensson, Kristina Svennerholm, Jacob Philipson, Aldina Pivodic, Sam Schulman, Mazdak Tavoly","doi":"10.1055/a-2402-6192","DOIUrl":"10.1055/a-2402-6192","url":null,"abstract":"<p><p>Recent data on temporal trends in excess mortality for patients with pulmonary embolism (PE) and deep vein thrombosis (DVT) compared with the general population are scarce.A nationwide Swedish register study conducted from 2006 to 2018 including 68,960 PE and 70,949 DVT cases matched with population controls. Poisson regression determined relative risk (RR) for 30-day and 1-year mortality trends while Cox regression determined adjusted hazard ratios (aHRs). A significance level of 0.001 was applied.In PE cases, both 30-day mortality (12.5% in 2006 to 7.8% in 2018, RR: 0.95 [95% CI: 0.95-0.96], <i>p</i> < 0.0001) and 1-year mortality (26.5 to 22.1%, RR: 0.98 [0.97-0.98], <i>p</i> < 0.0001) decreased during the study period. Compared with controls, no significant change was seen in 30-day (aHR: 33.08 [95% CI: 25.12-43.55] to 24.64 [95% CI: 18.81-32.27], <i>p</i> = 0.0015 for interaction with calendar year) or 1-year (aHR: 5.85 [95% CI: 5.31-6.45] to 7.07 [95% CI: 6.43-7.78], <i>p</i> = 0.038) excess mortality. The 30-day excess mortality decreased significantly (aHR: 39.93 [95% CI: 28.47-56.00) to 24.63 [95% CI: 17.94-33.83], <i>p</i> = 0.0009) in patients with PE without known cancer before baseline, while the excess 1-year mortality increased (aHR: 3.55 [95% CI: 3.16-3.99] to 5.38 [95% CI: 4.85-5.98], <i>p</i> < 0.0001) in PE cases surviving to fill a prescription of anticoagulation. In DVT cases, 30-day and 1-year mortality declined, while excess mortality compared with controls remained stable.In general, the improved mortality following PE and DVT paralleled population trends. However, PE cases without cancer had decreasing excess 30-day mortality, whereas those surviving to fill a prescription for anticoagulant medication showed increasing excess 1-year mortality.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"364-375"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factor XI Measurement in Acute Coronary Syndrome.","authors":"Diana A Gorog, Young-Hoon Jeong","doi":"10.1055/a-2546-2581","DOIUrl":"https://doi.org/10.1055/a-2546-2581","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754440","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":"Tissue Factor Pathway-Driven Initial Thrombin Generation is Associated with Hypercoagulability in Obesity.","authors":"Yuichi Kamikubo, Satomi Nagaya, Rina Inoue, Koichi Yamaguchi, Riyo Morimoto-Kamata, Kenichi Inoue, Eriko Morishita, Fahumiya Samad, Naoki Ohkura","doi":"10.1055/a-2552-2050","DOIUrl":"10.1055/a-2552-2050","url":null,"abstract":"<p><p>Initial thrombin (FIIa) generated via the tissue factor (TF) pathway plays a crucial role in amplifying coagulation. There is growing evidence that the TF pathway might contribute to hypercoagulation in obesity. However, it is unclear if the initial generation of FIIa (TG) is associated with hypercoagulation in obesity due to the lack of appropriate assays. This study aims to evaluate association between TF pathway-driven initial TG and hypercoagulability in obesity.We measured the initial TG levels in plasma from male Tsumura Suzuki obese diabetes (TSOD) mice and overweight subjects using the highly sensitive TG assay. To induce initial TG, TF was added to the plasma and incubated at 37°C for up to 3 minutes. After quenching the TG, we quantified the generated FIIa by kinetically monitoring its amidolytic activity with a fluorogenic substrate.We observed that initial TG levels were significantly higher in TSOD mice (<i>n</i> = 31) compared with non-obese mice (<i>n</i> = 32). Even in the absence of exogenous TF, initial TG levels in obese mice and overweight individuals were elevated when procoagulant phospholipids were added alone. Moreover, the increased initial TG that the inhibitory anti-TF antibody abolished was detectable in reconstituted plasma including pellets prepared by high-speed centrifugation of plasma from obese mice, not in plasma supernatant. We attributed the promotion of the initial TG to the increase in procoagulant TF-bearing microvesicles in circulation. Based on the findings, measuring TF pathway-driven initial TG could be a valuable method for assessing hypercoagulability in obesity.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573753","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":"Antithrombotic Therapy in People with Hemophilia-A Narrative Review.","authors":"Azusa Nagao, Shinichi Goto, Shinya Goto","doi":"10.1055/a-2548-4192","DOIUrl":"10.1055/a-2548-4192","url":null,"abstract":"<p><p>As the life expectancy of individuals with hemophilia continues to increase, the complexity of balancing bleeding risks and thrombotic management has become increasingly critical in people with hemophilia with or at a high risk of thrombosis. Advances in hemophilia therapies such as extended half-life coagulation factors, non-factor therapies, rebalancing agents, and gene therapy have expanded treatment options for a variety of people with hemophilia. The thrombotic risk of people with hemophilia in general are relatively low as compared to those without hemophilia. However, antithrombotic therapy for prevention and treatment for thrombosis should still be considered in some situations, even in hemophilia. This clinical focus highlights the use of antithrombotic therapy in the management of thrombosis in people with hemophilia. A multidisciplinary, personalized approach is essential for optimizing the safety and efficacy of antithrombotic therapy in people with hemophilia with or at a high risk of thrombosis. High performance computer based multidimensional data analysis may help in establishing the personalized antithrombotic therapy in the future.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531883","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":"Modifications of the Prothrombin Active Site S4 Subpocket Confer Resistance to Dabigatran.","authors":"Viola J F Strijbis, Ka Lei Cheung, Dejvid Veizaj, Tessa Rutten, Boris de Bruin, Pieter H Reitsma, Daniël Verhoef, Mettine H A Bos","doi":"10.1055/a-2537-6037","DOIUrl":"10.1055/a-2537-6037","url":null,"abstract":"<p><p>Direct anticoagulants inhibit coagulation serine proteases by reversibly engaging their active site with high affinity. By modifying the S4 active site subpocket of factor (F)Xa, we introduced inhibitor resistance while preserving catalytic activity. Given the homology between FXa and thrombin in active site architecture and direct anticoagulant binding, we have targeted the S4 subsite to introduce inhibitor resistance in (pro)thrombin.Recombinant prothrombin variants were generated in which I174 was substituted or sequence R92-N98 was exchanged with that of human kallikrein-3.Specific prothrombin clotting activity of the variants was 6-fold (intrinsic clotting) to 10-fold (extrinsic clotting) reduced relative to wild-type prothrombin. Further analyses revealed that modification of the S4 subsite hampers fibrinogen and thrombomodulin-mediated protein C conversion by thrombin. Consistent with this, the thrombin variants displayed a reduced catalytic efficiency toward the peptidyl substrate used in thrombin generation assessments. The variants displayed a 2-fold reduced sensitivity for dabigatran relative to wild-type prothrombin, while argatroban inhibition was unaffected. Analyses using a purified component system revealed an up to 24-fold and 4-fold reduced IC₅₀ for inhibition of thrombin by dabigatran and argatroban, respectively. Molecular dynamics (MD) simulations of both dabigatran-bound and unbound (apo) modified thrombin variants indicated these to comprise a larger inhibitor binding pocket relative to wild-type thrombin and display reduced inhibitor binding. As a net effect, (pro)thrombin variants with S4 subsite modifications supported detectable fibrin formation at therapeutic dabigatran concentrations.Our findings provide proof-of-concept for the engineering of thrombin variants that are resistant to direct thrombin inhibitors by modulating the S4 subsite.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410848","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":"Impact of Obesity and Overweight on Heparin Dosing and Clinical Outcomes in Pediatric Patients with Venous Thromboembolism.","authors":"Alexandra Larouche, Valérie Dollo, Gabriel Mercier, Narcisse Singbo, Chantal Éthier, Marie-Christine Boulanger, Marie-Claude Pelland-Marcotte","doi":"10.1055/a-2544-6183","DOIUrl":"https://doi.org/10.1055/a-2544-6183","url":null,"abstract":"<p><p>Dosing guidance for anticoagulation, the mainstay of venous thromboembolism (VTE) treatment, is lacking for obese children. We aimed to compare unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH) dosing requirements and clinical outcomes between obese/overweight and nonobese children.This monocentric retrospective cohort study included patients aged < 18 years old receiving anticoagulation for VTE. The outcomes were: (1) number of dose adjustments to reach therapeutic levels, (2) variation from initial dose, (3) thrombotic progression/recurrence, and (4) clinically relevant bleeding. Characteristics and dosing requirements of obese/overweight and nonobese children were compared using Pearson chi-square, Fisher exact, and Wilcoxon Mann-Whitney tests. Kaplan-Meier estimator compared the cumulative incidence of thrombotic recurrence/progression and clinically relevant bleeding between groups.We included 212 patients (median age: 6.2 years, 23.6% obese/overweight) having 258 anticoagulation encounters (LMWH: 82.6%, UFH: 17.4%). Most children had therapeutic levels following one dosage (66.7% in obese/overweight vs. 51.8% in nonobese, <i>p</i> = 0.201). Dosing requirements significantly differed between obese/overweight and nonobese children (average increase from initial dose: 3.2 vs. 11.3%, <i>p</i> < 0.001). In obese/overweight children, 11.1% of patients required ≥ 10% dose reduction versus 2.1% in nonobese children (<i>p</i> < 0.001). The cumulative incidence of thrombotic progression/recurrence was comparable between groups (obese/overweight: 12.0%, nonobese: 10.5%, <i>p</i> = 0.786). Similarly, clinically significant bleeding was rare for both groups (obese/overweight: 2.0%, nonobese: 3.1%, <i>p</i> = 0.609).In children treated for VTE, obesity/overweight was associated with lower anticoagulation requirements. Further prospective work is urgently needed to explore alternate regimens, such as dose capping, reduced initial dosing, or the use of fat-free mass.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701646","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}