Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Prognostic relevance of early clinical and laboratory findings in immune-mediated thrombotic thrombocytopenic purpura.","authors":"Atsushi Hamamura, Kazuya Sakai, Toshiki Mushino, Yasunori Ueda, Yoshiyuki Ogawa, Hiroyuki Noguchi, Akinao Okamoto, Hideo Yagi, Takehiko Mori, Masanori Matsumoto","doi":"10.1016/j.rpth.2025.102974","DOIUrl":"10.1016/j.rpth.2025.102974","url":null,"abstract":"<p><strong>Background: </strong>Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening condition caused by a severe deficiency of a disintegrin and metalloproteinase with thrombospondin type 1 motif 13 due to autoantibodies. Despite modern treatments, including therapeutic plasma exchange, immunosuppression, and rituximab, early mortality-often due to cardiac and neurologic events-remains a concern.</p><p><strong>Methods: </strong>We analyzed data from 125 patients between 2010 and 2023 in the Japanese thrombotic thrombocytopenic purpura (TTP) registry, examining demographics, electrocardiogram and transthoracic echocardiography findings, and neurologic symptoms. Troponin I was measured. Outcomes were categorized as survivors, TTP-related deaths, and non-TTP-related deaths.</p><p><strong>Results: </strong>Of the 125 patients, 15 died, with 5 deaths directly related to iTTP. Early cardiac findings and neurologic symptoms were not significant predictors of mortality. However, elevated lactate dehydrogenase levels and reduced von Willebrand factor multimer indices correlated with poorer prognosis. Patients with myocardial hypokinesis finally recovered their condition during the course of treatment. No patient treated with caplacizumab died during the observation period.</p><p><strong>Conclusions: </strong>These findings suggest that early cardiac and neurologic symptoms may not be definitive predictors of iTTP-related death. Instead, extremely high lactate dehydrogenase levels indicated a worse prognosis, highlighting the need for targeted monitoring and interventions in high-risk cases.</p>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"102974"},"PeriodicalIF":3.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"R<b>ole of polygenic risk scores in venous thromboembolism: current state and future direc</b> <b>tions</b>.","authors":"Aman Goyal, Sonia Hurjkaliani, Kevin Michael Alexander, Jianfeng Xu, Manan Pareek, Arman Qamar","doi":"10.1016/j.rpth.2025.102973","DOIUrl":"10.1016/j.rpth.2025.102973","url":null,"abstract":"<p><p>Venous thromboembolism (VTE) is a significant global health concern, with >1 million cases annually in the United States, making it a leading cause of preventable hospital-related deaths. Advances in genetic research, particularly genome-wide association studies, have demonstrated the polygenic nature of VTE by identifying numerous single-nucleotide polymorphisms associated with susceptibility. The polygenic risk score (PRS), which aggregates the effects of multiple single-nucleotide polymorphisms, has emerged as a valuable tool for improving VTE risk assessment. Recent studies have demonstrated that PRS significantly improves VTE risk prediction beyond traditional clinical factors. Integrating genetic and clinical data enhances predictive accuracy, with individuals at high risk identified by PRS showing nearly 8 times the VTE risk of those at low risk. Additionally, PRS models have been developed to predict VTE risk in various predisposing conditions, including malignancies, cardiometabolic disorders, and pulmonary hypertension. These findings indicate that PRS could inform thromboprophylaxis decisions for high-risk patients. Further evidence indicates that PRS improves VTE risk prediction, even in individuals without conventional risk factors, such as family history or lifestyle contributors. The future of PRS in VTE risk stratification is promising, offering refined risk assessment, optimized anticoagulation management, and tailored thromboprophylaxis. However, challenges persist, including the development of multiancestry PRS models to enhance predictive accuracy across diverse populations. Continued research and validation will be essential to unlocking the full clinical potential of PRS in VTE management.</p>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"102973"},"PeriodicalIF":3.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TSUBASA study: evaluation of the quality and content of daily life of people with hemophilia A without factor VIII inhibitors on prophylactic treatment with emicizumab.","authors":"Teruhisa Fujii, Keiji Nogami, Akihiro Sawada, Azusa Nagao, Chiai Nagae, Masanori Nojima, Nobuaki Suzuki, Mika Kawano, Tomomi Shimura, Yoshimasa Sugao, Kagehiro Amano","doi":"10.1016/j.rpth.2025.102971","DOIUrl":"10.1016/j.rpth.2025.102971","url":null,"abstract":"<p><strong>Background: </strong>Hemophilia A (HA) negatively impacts quality of life (QoL). Treatment with the bispecific antibody emicizumab has shown efficacy and safety in people with HA in clinical trials, but long-term QoL data are limited.</p><p><strong>Objectives: </strong>To investigate the QoL of people with HA receiving emicizumab over 97 weeks in the prospective, observational TSUBASA study in Japan.</p><p><strong>Methods: </strong>Data were collected from participants aged ≥6 years with HA without factor VIII inhibitors and caregivers of participants of any age from November 2019 to October 2023. Quality of daily life was measured via the 36-Item Short Form Health Survey, the International Physical Activity Questionnaire, the Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questionnaire: Hemophilia Specific, and a survey-based questionnaire evaluating daily life, completed by the participant and their caregiver.</p><p><strong>Results: </strong>Overall, 104 participants aged ≥6 years were enrolled. The median (range) age was 39.0 (6-73) years. Eighty-five (81.7%) participants had severe HA; 21 (20.2%) had target joints. The 36-Item Short Form Health Survey scores were mostly unchanged across the study period and comparable with Japanese national standard values. The proportion of participants engaging in high physical activity increased from 20.2% to 27.3% between baseline and week 97. The Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questionnaire: Hemophilia Specific scores were generally stable. The questionnaires showed improvements in activity, motivation for work/school, and bleed anxiety, as judged by participants and caregivers.</p><p><strong>Conclusion: </strong>QoL outcomes remained largely unchanged across the study period. Notable improvements were observed in physical activity levels, motivation for work/school, and anxiety related to bleeding, as reported by participants and caregivers.</p>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"102971"},"PeriodicalIF":3.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrinography and thrombography (thrombodynamics-4D) in atrial fibrillation assessment of direct oral anticoagulants in geriatrics patients aged 80 years and older receiving direct oral anticoagulant therapy.","authors":"Geoffrey Foulon-Pinto, Georges Jourdi, Maxime Delrue, Carmelo Lafuente-Lafuente, Candice Cavalie, Isabelle Gouin-Thibault, Julien Le Guen, Pascale Gaussem, Tristan Mirault, Etienne Puymirat, Thomas Lecompte, Eric Pautas, Emmanuel Curis, Virginie Siguret","doi":"10.1016/j.rpth.2025.102969","DOIUrl":"10.1016/j.rpth.2025.102969","url":null,"abstract":"<p><strong>Background: </strong>Scarce data are available on pharmacodynamic (PD) variability in very elderly patients receiving direct oral anticoagulants (DOACs) for atrial fibrillation (AF). Thrombodynamics-4D (TD-4D), which simultaneously assesses fibrin clot formation and thrombin generation, has not yet been tested in patients on rivaroxaban, apixaban, or dabigatran.</p><p><strong>Objectives: </strong>To (i) evaluate TD-4D's ability to assess DOAC effect added to normal plasma; (ii) assess DOAC PD in very elderly patients with AF along with DOAC concentrations; (iii) identify factors associated with interindividual variability of DOAC PD at peak and trough levels.</p><p><strong>Methods: </strong>Assessment of Direct oral Anticoagulants in Geriatrics (NCT02464488) is a prospective, multicenter study including inpatients aged ≥80 years receiving DOACs for AF for at least 4 days. Fibrinography and thrombography parameters were measured using TD-4D along with plasma DOAC concentrations (antifactor [F]Xa or anti-FIIa activity) and fibrinogen.</p><p><strong>Results: </strong>We analyzed pooled normal plasma samples spiked with DOACs and 345 samples from 187 Assessment of Direct oral Anticoagulants in Geriatrics patients (mean ± SD, age 87 ± 4 years; 69% females): 69 on rivaroxaban, 70 on apixaban, and 48 on dabigatran. All 3 DOACs prolonged fibrinography lag time and decreased initial rate of clot growth and clot size at 30 minutes in a concentration-dependent manner in spiking experiments and patients. DOACs prolonged temporal thrombography parameters while decreasing thrombin peak height and endogenous thrombin potential. At trough, apixaban and dabigatran concentrations were the only significant predictors of interindividual variability in both thrombin peak height (thrombography) and initial rate of clot growth (fibrinography). In rivaroxaban patients, cardiac failure significantly influenced thrombin peak height variability.</p><p><strong>Conclusion: </strong>Fibrinography and thrombography, assessed simultaneously with TD-4D, provided consistent results for all 3 DOACs, including dabigatran. Substantial PD variability was observed, partly influenced by DOAC concentrations. The clinical relevance of such variability remains to be demonstrated.</p>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"102969"},"PeriodicalIF":3.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serotonin transporter deficiency, but not absence of platelet serotonin, impairs thrombus formation in a model of deep vein thrombosis.","authors":"Katharina Naber, Maximilian Mauler, Nancy Schanze, Pia Kröning, Daniela Stallmann, Daniel Duerschmied, Dirk Westermann, Nadine Gauchel","doi":"10.1016/j.rpth.2025.102970","DOIUrl":"10.1016/j.rpth.2025.102970","url":null,"abstract":"<p><strong>Background: </strong>The majority of peripheral serotonin is stored in dense granules of circulating blood platelets and released upon platelet activation. Recently, an immunomodulatory role of serotonin in inflammation has been found, influencing the recruitment of leukocytes, especially neutrophils.</p><p><strong>Objectives: </strong>Since deep vein thrombosis creates an inflammatory milieu, called thromboinflammation, this study examined the impact of peripheral platelet serotonin on the development of venous thrombosis.</p><p><strong>Methods: </strong>To induce deep vein thrombosis, a stenosis model of the inferior vena cava was used. Six- to 8-week-old C57BL/6 (wild-type [WT]), selective serotonin reuptake inhibitor-treated C57BL/6 (depleted serotonin pools in platelets), serotonin transporter knockout (SERT^-/-), and tryptophan hydroxylase 1 knockout (Tph1^-/-) mice were used. Thrombus volume was measured, and its composition was analyzed after 48 hours using immunofluorescence microscopy. Neutrophils and platelet-neutrophil complexes were analyzed using flow cytometry.</p><p><strong>Results: </strong>SERT^-/- mice formed significantly fewer and smaller thrombi compared with WT (mean ± SD, 1.09 mm³ ± 2.53 vs 13.1 mm³ ± 11.1; <i>P</i> = .002) and Tph1^-/- mice (1.09 mm³ ± 2.53 vs 11.3 mm³ ± 6.84; <i>P</i> = .02) and had lower levels of neutrophils in the blood. Thrombi in the WT and Tph1^-/- groups were comparable. In SERT^-/- mice, there was no decrease in circulating platelet-neutrophil complexes.</p><p><strong>Conclusion: </strong>The extent of venous thrombosis did not depend on peripheral serotonin in our mouse model, but rather on the presence of the serotonin transporter. In the absence of the serotonin transporter, the thrombogenic property as well as the overall immune response to venous thrombosis was reduced. The distribution of the serotonin transporter on immune cells and its thrombogenic potential should be studied further.</p>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"102970"},"PeriodicalIF":3.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The thrombotic paradox in congenital fibrinogen deficiencies: from pathophysiology to practice","authors":"Samin Mohsenian ,&nbsp;Alessandro Casini ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2025.102979","DOIUrl":"10.1016/j.rpth.2025.102979","url":null,"abstract":"<div><div>Congenital fibrinogen deficiencies (CFDs) comprise rare inherited disorders characterized by quantitative (afibrinogenemia, hypofibrinogenemia) or qualitative (dysfibrinogenemia, hypodysfibrinogenemia) abnormalities of fibrinogen. While CFDs are typically associated with bleeding, a paradoxical risk of both arterial and venous thrombosis is being increasingly recognized. Proposed mechanisms include impaired thrombin clearance due to a lack of fibrin formation and structurally abnormal fibrin clots that promote thrombin release into the circulation or hinder fibrinolysis. In afibrinogenemia, the absence of fibrinogen leads to increased circulating free thrombin, while in dysfibrinogenemia, structurally abnormal fibrinogen enhances thrombotic risk. Intrinsic factors such as specific fibrinogen variants (eg, Dusart, Bordeaux) alter the fibrin structure and impair thrombin or plasmin interactions, thus promoting abnormal clot formation and reduced fibrinolysis. Coinherited prothrombotic mutations may further increase thrombotic risk. Moreover, acquired factors, including fibrinogen replacement therapy, surgery, trauma, pregnancy, and immobilization, are recognized extrinsic risk factors. The pathogenesis of thrombosis in CFDs is multifactorial and not fully elucidated. Managing thrombosis in CFDs is a clinical challenge, requiring careful balance between the risk of bleeding and thrombosis. Anticoagulation alongside fibrinogen replacement may be necessary, but must be individualized. Although fibrinogen replacement primarily carries prothrombotic potential, some studies suggest it may improve thrombin regulation in afibrinogenemia. Notably, current evidence is limited and mostly derived from case reports. This review provides an overview of the existing evidence on the epidemiology, underlying mechanisms, and clinical management of thrombosis in CFDs, highlighting knowledge gaps and the need for additional research to inform clinicians and improve patient outcomes.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102979"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factor XI levels and the risk of cardiovascular events: a systematic review and meta-analysis of case-control and cohort studies","authors":"Wenchi Li ,&nbsp;Qimin Ma ,&nbsp;Wei Zhou ,&nbsp;Feng Zhu","doi":"10.1016/j.rpth.2025.102968","DOIUrl":"10.1016/j.rpth.2025.102968","url":null,"abstract":"<div><h3>Background</h3><div>The relationship between coagulation factor (F)XI and the risk of cardiovascular events has been investigated in several epidemiological studies, but the overall results remain inconclusive.</div></div><div><h3>Objectives</h3><div>The aim of this systematic review and meta-analysis of case-control and cohort studies was to evaluate the relationship between FXI and the risk of cardiovascular events. FXI levels in the general population and the risk of different cardiovascular events were the primary exposure and outcome, respectively.</div></div><div><h3>Methods</h3><div>Two independent reviewers (Li and Ma) screened all available literature to identify studies that met the inclusion criteria. A random or fixed-effects model was used, and heterogeneity was quantitatively tested by the <em>I</em>² statistic.</div></div><div><h3>Results</h3><div>A total of 16 original studies were included in the quantitative meta-analysis. The meta-analysis results of both case-control and cohort studies showed a positive correlation between FXI levels and the risk of cardiovascular events (odds ratio [OR], 1.77; 95% CI, 1.17-2.68; hazard ratio [HR], 1.34; 95% CI, 1.09-1.64). Subgroup analysis revealed a positive correlation between FXI levels and the risk of myocardial infarction (OR, 1.63; 95% CI, 1.02-2.60; HR, 2.53; 95% CI, 1.15-5.60), while there was no significant correlation between FXI levels and acute coronary syndrome or ischemic stroke (OR, 1.78; 95% CI, 0.40-7.82; HR, 1.15; 95% CI, 0.93-1.41).</div></div><div><h3>Conclusion</h3><div>Our findings support a positive correlation between FXI levels and the risk of cardiovascular events.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102968"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bleeding and thrombosis in intestinal transplantation; data from 145 consecutive adult transplants","authors":"Francesca Reeder ,&nbsp;Jessica Griffin ,&nbsp;Matthew Carter ,&nbsp;Holly Lowing ,&nbsp;Praharsh Babu ,&nbsp;Andrew Quarrell ,&nbsp;Tracy Moore ,&nbsp;Theodora Foukaneli ,&nbsp;Martin Besser ,&nbsp;Irum Amin ,&nbsp;Jeremy Woodward ,&nbsp;Neil Russell ,&nbsp;Dunecan Massey ,&nbsp;Rohit Gaurav ,&nbsp;Lisa Sharkey ,&nbsp;Charlotte Rutter ,&nbsp;Andrew Butler ,&nbsp;Will Thomas","doi":"10.1016/j.rpth.2025.102990","DOIUrl":"10.1016/j.rpth.2025.102990","url":null,"abstract":"<div><h3>Background</h3><div>Cambridge University Hospitals NHS Foundation Trust provides an adult intestinal/multivisceral transplant service to the United Kingdom. These patients can have complex thrombotic histories and are at risk of bleeding and thrombosis posttransplant.</div></div><div><h3>Objectives</h3><div>We describe our experience of (a) bleeding and thrombosis posttransplant, (b) transplantation for acute abdominal vascular catastrophe, and (c) use of direct oral anticoagulants (DOACs) posttransplant.</div></div><div><h3>Methods</h3><div>A retrospective study of recipients of intestinal transplants at our center between 2007 and June 2023 was conducted.</div></div><div><h3>Results</h3><div>Of 138 recipients (who received 145 grafts), 96 (70%) had a history of thrombosis pretransplant. Of the 145 grafts, 138 (95%) received blood products in the immediate operative period (up to 24 hours postoperatively; day +1) and 6 of 145 (4%) had an intraoperative thrombosis. Major bleeding and thrombosis rates from day +2 to +92 posttransplant were 38.0% (95% CI, 30.0%-46.0%) and 26.1% (95% CI, 19.1%-33.5%), respectively. Bleeds were predominantly gastrointestinal, surgical site, or intra-abdominal. The majority of thromboses (32 of 38 [84%]) were venous (especially catheter associated). No particular relationship between thrombotic and bleeding complications was observed. Eight recipients were transplanted as salvage procedures due to abdominal vascular catastrophe with generally favorable results, although in 3 recipients, no etiology was identified, and anticoagulant failures were seen. Five received DOACs posttransplant, and adequate peak drug levels were seen without bleeding or thrombotic complications.</div></div><div><h3>Conclusion</h3><div>Patients who undergo intestinal transplant are at high risk of bleeding and thrombosis posttransplant. Intestinal transplant was used successfully as a salvage treatment for acute abdominal vascular catastrophe. DOACs were used in selected posttransplant patients. Further multicenter studies are required.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102990"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inherited thrombophilia in a Han Chinese family caused by prothrombin Ile441Met mutation","authors":"Si-Yuan Wen ,&nbsp;Fei-Fei Chen ,&nbsp;Ji-De Chen ,&nbsp;Pan Tao ,&nbsp;Chi Meng ,&nbsp;Jing Huang ,&nbsp;Xin Kang ,&nbsp;Wei Chen ,&nbsp;Chang-Qing Zhou","doi":"10.1016/j.rpth.2025.102987","DOIUrl":"10.1016/j.rpth.2025.102987","url":null,"abstract":"<div><h3>Background</h3><div>Inherited thrombophilia (IT) is a genetically determined predisposition to thromboembolic events. Beyond the well-known G20210A mutation, there has been limited research on other prothrombin mutations in the Chinese population.</div></div><div><h3>Objectives</h3><div>This study aimed to identify and characterize a novel prothrombin mutation in a Han Chinese family with IT.</div></div><div><h3>Methods</h3><div>Clinical information was collected from the proband and his related family members. Coagulation tests, including protein S, plasminogen, protein C, and antithrombin Ⅲ activities, were conducted. Whole-genome sequencing was conducted on the proband and his mother to identify the causative mutation, and suspected mutations were verified in other family members using whole-exon sequencing. Thrombin generation assay was performed to evaluate hypercoagulable states.</div></div><div><h3>Results</h3><div>Among the 53 family members, 11 individuals had a history of venous thromboembolism (VTE). Genetic analysis of 9 family members identified a novel heterozygous prothrombin mutation, p.Ile441Met (c.1323A&gt;G), in 6 individuals with VTE history. These mutation carriers exhibited various forms of VTE, predominantly pulmonary embolism and lower-limb deep vein thrombosis. Routine coagulation tests showed no significant abnormalities in prothrombin time and activated partial thromboplastin time, while 5 carriers exhibited decreased protein S activity. Thrombin generation assay revealed a hypercoagulable state, characterized by shortened lag time, increased thrombin peak, and elevated endogenous thrombin potential.</div></div><div><h3>Conclusion</h3><div>The Ile441Met mutation is a novel prothrombin mutation associated with IT in the Han Chinese population, which induces a hypercoagulable state, leading to various forms of VTE. Further studies are needed to validate these findings and investigate the underlying pathogenic mechanisms.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102987"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low concentrations of recombinant activated factor VII normalize coagulation patterns by reversing the changes in viscoelastic testing parameters induced by abelacimab in vitro","authors":"Yasser Khder ,&nbsp;Serge Côté ,&nbsp;Klaus Peter Hoffmann ,&nbsp;Debra Freedholm ,&nbsp;Dan Bloomfield ,&nbsp;Jean M. Connors","doi":"10.1016/j.rpth.2025.102976","DOIUrl":"10.1016/j.rpth.2025.102976","url":null,"abstract":"<div><h3>Background</h3><div>Low doses of recombinant activated factor (F)VII (rFVIIa), used to manage bleeding in patients with severe FXI deficiency, have been proposed to bypass effects of the FXI/FXIa inhibitor abelacimab.</div></div><div><h3>Objectives</h3><div>To test whether low concentrations of rFVIIa could abolish changes in coagulation parameters induced by abelacimab as measured by rotational thromboelastometry.</div></div><div><h3>Methods</h3><div>Whole blood specimens obtained in citrated tubes from 6 healthy donors were incubated with 15 and 30 μg/mL of abelacimab or vehicle for 10 minutes at 37 °C. Specimens were subsequently spiked with rFVIIa at 0.5 and 1 μg/mL or vehicle. Clot formation was monitored using rotational thromboelastometry delta analyzers and the nonactivated thromboelastometry test. Clotting time (CT, in seconds), clot formation time (CFT, in seconds), α angle, etc. were measured and compared with vehicle (excipient solution containing His/His-HCl, sucrose, polysorbate 20 solution) and reference ranges provided by the manufacturer.</div></div><div><h3>Results</h3><div>Abelacimab at 15 and 30 μg/mL concentrations increased CT by 61% and 64%, CFT by 37% and 32%, and decreased α angle by 10% and 14% compared with baseline, respectively. Adding rFVIIa at 0.5 and 1.0 μg/mL shortened CT by 21% and 38%, CFT by 33% and 49%, and increased α angle by 29% and 47%, respectively. Nonactivated thromboelastometry parameters generally remained within normal reference ranges when rFVIIa was added.</div></div><div><h3>Conclusion</h3><div>Low concentrations of rFVIIa (0.5-1 μg/mL) corrected the effects of abelacimab as assessed by rotational thromboelastometry. Our data support using low doses of rFVIIa for bleeding management in patients treated with abelacimab.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102976"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}