Thrombosis and haemostasis最新文献

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Shifting Priorities in the Prevention of Venous Thromboembolism: Time to Focus on Overall Cardiovascular Health. 转变静脉血栓栓塞症预防工作的重点:是时候关注整体心血管健康了。
IF 5 2区 医学
Thrombosis and haemostasis Pub Date : 2024-10-01 Epub Date: 2024-08-12 DOI: 10.1055/s-0044-1788926
Stavros V Konstantinides
{"title":"Shifting Priorities in the Prevention of Venous Thromboembolism: Time to Focus on Overall Cardiovascular Health.","authors":"Stavros V Konstantinides","doi":"10.1055/s-0044-1788926","DOIUrl":"10.1055/s-0044-1788926","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"958-961"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971912","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}
引用次数: 0
Lack of Formyl-peptide Receptor 1 Mitigates Atherosclerosis in Hyperlipidemic Mice. 缺乏甲酰肽受体 1 可减轻高脂血症小鼠的动脉粥样硬化
IF 5 2区 医学
Thrombosis and haemostasis Pub Date : 2024-10-01 Epub Date: 2024-05-23 DOI: 10.1055/s-0044-1787264
Yvonne Döring, Alexander Bender, Oliver Soehnlein
{"title":"Lack of Formyl-peptide Receptor 1 Mitigates Atherosclerosis in Hyperlipidemic Mice.","authors":"Yvonne Döring, Alexander Bender, Oliver Soehnlein","doi":"10.1055/s-0044-1787264","DOIUrl":"10.1055/s-0044-1787264","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"986-989"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087793","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}
引用次数: 0
Obesity-Related Traits Mediate the Effects of Educational Attainment on the Risk of Varicose Veins, Venous Thromboembolism, and Phlebitis. 与肥胖有关的特质可调节教育程度对静脉曲张、静脉血栓栓塞症和静脉炎风险的影响。
IF 5 2区 医学
Thrombosis and haemostasis Pub Date : 2024-10-01 Epub Date: 2024-05-10 DOI: 10.1055/s-0044-1786970
Hong-Cheng Du, Bai-Yang Deng
{"title":"Obesity-Related Traits Mediate the Effects of Educational Attainment on the Risk of Varicose Veins, Venous Thromboembolism, and Phlebitis.","authors":"Hong-Cheng Du, Bai-Yang Deng","doi":"10.1055/s-0044-1786970","DOIUrl":"10.1055/s-0044-1786970","url":null,"abstract":"<p><strong>Background: </strong> The extent to which educational attainment (EA) influences the risk of varicose veins (VVs), venous thromboembolism (VTE), and phlebitis occurrence, whether this pathway is mediated by obesity-related traits, and the proportion of their mediation is unknown.</p><p><strong>Methods: </strong> A Mendelian randomization (MR) design was used to genetically investigate the causal effects of EA on the risk of VV, VTE, and phlebitis and to assess the mediating effect of obesity-related traits. Causal effects were estimated using primarily the multiplicative random-effects inverse variance-weighted method. This was supplemented by Cochran's Q-statistic, MR-Egger regression, MR funnel plots, and leave-one-out test to evaluate the reliability of the results. For the individual mediation effect, the coefficient product method was mainly utilized to estimate.</p><p><strong>Results: </strong> An increase in genetically predicted EA was associated with a lower risk of VV, VTE, and phlebitis, as well as lower body mass index, basal metabolic rate, hip circumference, and waist circumference. As genetically predicted body mass index, basal metabolic rate, hip circumference, and waist circumference increased, the risk of developing VV, VTE, and phlebitis increased, respectively. Body mass index, basal metabolic rate, hip circumference, and waist circumference were identified as mediators of the protective effects of EA on VV, VTE, and phlebitis.</p><p><strong>Conclusion: </strong> The findings support a causal relationship between higher EA and lower risk of VV, VTE, and phlebitis. Obesity-related traits play a significant mediating role in these pathways, and there are interactions between them, with hip circumference mediating these pathways relatively independently from the other three.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"962-970"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905140","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}
引用次数: 0
2024 Chinese Expert Consensus Guidelines on the Diagnosis and Treatment of Atrial Fibrillation in the Elderly, Endorsed by Geriatric Society of Chinese Medical Association (Cardiovascular Group) and Chinese Society of Geriatric Health Medicine (Cardiovascular Branch): Executive Summary. 2024 中国老年心房颤动诊断和治疗专家共识指南。内容摘要。
IF 5 2区 医学
Thrombosis and haemostasis Pub Date : 2024-10-01 Epub Date: 2024-05-14 DOI: 10.1055/a-2325-5923
Yutang Wang, Yutao Guo, Mingzhao Qin, Jin Fan, Ming Tang, Xinjun Zhang, Hao Wang, Xiaoying Li, Gregory Y H Lip
{"title":"2024 Chinese Expert Consensus Guidelines on the Diagnosis and Treatment of Atrial Fibrillation in the Elderly, Endorsed by Geriatric Society of Chinese Medical Association (Cardiovascular Group) and Chinese Society of Geriatric Health Medicine (Cardiovascular Branch): Executive Summary.","authors":"Yutang Wang, Yutao Guo, Mingzhao Qin, Jin Fan, Ming Tang, Xinjun Zhang, Hao Wang, Xiaoying Li, Gregory Y H Lip","doi":"10.1055/a-2325-5923","DOIUrl":"10.1055/a-2325-5923","url":null,"abstract":"<p><p>The consensus guidelines of the Geriatric Society of Chinese Medical Association on the management of atrial fibrillation (AF) in the elderly was first published in 2011 and updated in 2016, with endorsement by Chinese Society of Geriatric Health Medicine. Since then, many important studies regarding the screening and treatment in the elderly population have been reported, necessitating this updated expert consensus guideline. The writing committee members comprehensively reviewed updated evidence pertaining to elderly patients with AF, and formulated this 2024 update. The highlighted issues focused on the following: screening for AF, geriatric comprehensive assessment, use of the Atrial fibrillation Better Care (ABC) pathway for the elderly patients, and special clinical settings related to elderly patients with AF. New recommendations addressing smart technology facilitated AF screening, ABC pathway based management, and optimal anticoagulation were developed, with a focus on the elderly.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"897-911"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923250","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}
引用次数: 0
Field Study and Correlative Studies of Factor IX Variant FIX-R338L in Participants Treated with Fidanacogene Elaparvovec. 对接受 Fidanacogene Elaparvovec 治疗的参与者进行因子 IX 变体 FIX-R338L 的实地研究和相关研究。
IF 5 2区 医学
Thrombosis and haemostasis Pub Date : 2024-10-01 Epub Date: 2024-06-11 DOI: 10.1055/s-0044-1787734
Debra D Pittman, Charles Carrieri, Holly Soares, John McKay, Charles Y Tan, John Z Liang, Swapnil Rakhe, Jean-Claude Marshall, John E Murphy, Puneet Gaitonde, Jeremy Rupon
{"title":"Field Study and Correlative Studies of Factor IX Variant FIX-R338L in Participants Treated with Fidanacogene Elaparvovec.","authors":"Debra D Pittman, Charles Carrieri, Holly Soares, John McKay, Charles Y Tan, John Z Liang, Swapnil Rakhe, Jean-Claude Marshall, John E Murphy, Puneet Gaitonde, Jeremy Rupon","doi":"10.1055/s-0044-1787734","DOIUrl":"10.1055/s-0044-1787734","url":null,"abstract":"<p><strong>Background: </strong> Fidanacogene elaparvovec, an adeno-associated virus-based gene therapy vector expressing the high-activity factor IX (FIX) variant FIX-R338L, is in development for hemophilia B. One-stage clotting (OS) assays and chromogenic substrate (CS) assays are commonly used to measure FIX-R338L variant activity. Data from ongoing trials suggest FIX activity varies between different OS and CS assays.</p><p><strong>Material and methods: </strong> To better understand FIX-R338L activity in clinical samples, an international multisite field study was conducted across a central laboratory and 18 local laboratories, using standard protocols, reagents, and instrumentation, with individual participant samples from a phase 1/2a study of fidanacogene elaparvovec.</p><p><strong>Results: </strong> Unlike the wild-type FIX control, FIX-R338L activity was higher with the OS silica-based assay versus OS ellagic acid-based and CS assays. Variation in FIX activity was greater at the lowest activity levels. Activated FIX (FIXa) in plasma could result in higher OS assay activity or increased thrombin generation, which could overestimate FIX activity. However, FIXa was not detected in the participant samples, indicating that it was not contributing to the OS assay differences. Since individuals on gene therapy may receive exogenous replacement FIX products, replacement products were spiked into patient plasma samples to target a therapeutic concentration. Exogenous FIX was additive to endogenous FIX-R338L, with no interference from FIX-R338L.</p><p><strong>Conclusion: </strong> These results demonstrate FIX-R338L activity can be measured with OS and CS assays in clinical laboratories and provide insight into assay variability when measuring FIX with endogenously produced FIX-R338L. The findings may help establish best practices for measuring FIX-R338L activity (Clinicaltrials.gov identifier: NCT02484092).</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"912-921"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306894","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}
引用次数: 0
Characteristics of Bleeding Complications in Patients with Severe COVID-19 Requiring Veno-venous Extracorporeal Membrane Oxygenation in Japan. 日本需要静脉-静脉体外膜氧合的重度 COVID19 患者出血并发症的特征。
IF 5 2区 医学
Thrombosis and haemostasis Pub Date : 2024-09-27 DOI: 10.1055/a-2411-1000
Hayato Taniguchi, Takeru Abe, Ichiro Takeuchi, Shinichiro Ohshimo, Nobuaki Shime, Shigeki Kushimoto, Satoru Hashimoto, Shinhiro Takeda
{"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><strong>Background: </strong> 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.</p><p><strong>Methods: </strong> 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.</p><p><strong>Results: </strong> 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).</p><p><strong>Conclusion: </strong> 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":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Carbamylation-A Pathologic Posttranslational Modification Affecting Platelet and Von Willebrand Factor Function during Uremic Kidney Disease. 氨甲酰化--尿毒症肾病期间影响血小板和Von Willebrand因子功能的病理性翻译后修饰
IF 5 2区 医学
Thrombosis and haemostasis Pub Date : 2024-09-27 DOI: 10.1055/s-0044-1791550
Rory R Koenen
{"title":"Carbamylation-A Pathologic Posttranslational Modification Affecting Platelet and Von Willebrand Factor Function during Uremic Kidney Disease.","authors":"Rory R Koenen","doi":"10.1055/s-0044-1791550","DOIUrl":"https://doi.org/10.1055/s-0044-1791550","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354311","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}
引用次数: 0
Reversible Thrombocytopenia of Functional Platelets after Nose-Horned Viper Envenomation Is Induced by a Snaclec. 鼻角蝰中毒后功能性血小板可逆性减少是由 Snaclec 诱导的。
IF 5 2区 医学
Thrombosis and haemostasis Pub Date : 2024-09-23 DOI: 10.1055/a-2408-9375
Mojca Dobaja Borak, Adrijana Leonardi, Kity Požek, Katarina Reberšek, Helena Podgornik, Aljaž Pirnat, Alenka Trampuš Bakija, Simona Kranjc Brezar, Tomaž Trobec, Monika C Žužek, Robert Frangež, Miran Brvar, Igor Križaj
{"title":"Reversible Thrombocytopenia of Functional Platelets after Nose-Horned Viper Envenomation Is Induced by a Snaclec.","authors":"Mojca Dobaja Borak, Adrijana Leonardi, Kity Požek, Katarina Reberšek, Helena Podgornik, Aljaž Pirnat, Alenka Trampuš Bakija, Simona Kranjc Brezar, Tomaž Trobec, Monika C Žužek, Robert Frangež, Miran Brvar, Igor Križaj","doi":"10.1055/a-2408-9375","DOIUrl":"10.1055/a-2408-9375","url":null,"abstract":"<p><p>Profound and transient thrombocytopenia of functional platelets without bleeding was observed in patients envenomed by <i>Vipera a. ammodytes</i> (<i>Vaa</i>). This condition was rapidly reversed by administration of F(ab)<sub>2</sub> fragments of immunoglobulin G targeting the whole venom, leaving platelets fully functional. To investigate the potential role of snake venom C-type lectin-like proteins (snaclecs) in this process, <i>Vaa</i>-snaclecs were isolated from the crude venom using different liquid chromatographies. The purity of the isolated proteins was confirmed by Edman sequencing and mass spectrometry. The antithrombotic effect was investigated by platelet agglutination and aggregation assays and blood coagulation tests. Using flow cytometry, the platelet activation and binding of <i>Vaa</i>-snaclecs to various platelet receptors was analyzed. Antithrombotic efficacy was tested in vivo using a mouse model of vascular injury. Two <i>Vaa</i>-snaclecs were purified from the venom. One of them, <i>Vaa</i>-snaclec-3/2, inhibited ristocetin-induced platelet agglutination. It is a covalent heterodimer of <i>Vaa</i>-snaclec-3 (α-subunit) and <i>Vaa</i>-snaclec-2 (β-subunit). Our results suggest that <i>Vaa</i>-snaclec-3/2 induces platelet agglutination and consequently thrombocytopenia by binding to the platelet receptor glycoprotein Ib. Essentially, no platelet activation was observed in this process. In vivo, <i>Vaa</i>-snaclec-3/2 was able to protect the mouse from ferric chloride-induced carotid artery thrombosis, revealing its applicative potential in interventional angiology and cardiology.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126722","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}
引用次数: 0
Harnessing Risk Assessment for Thrombosis and Bleeding to Optimize Anticoagulation Strategy in Nonvalvular Atrial Fibrillation. 利用血栓和出血风险评估优化非瓣膜性心房颤动的抗凝策略。
IF 5 2区 医学
Thrombosis and haemostasis Pub Date : 2024-09-19 DOI: 10.1055/a-2385-1452
Yue Zhao, Li-Ya Cao, Ying-Xin Zhao, Di Zhao, Yi-Fan Huang, Fei Wang, Qian Wang
{"title":"Harnessing Risk Assessment for Thrombosis and Bleeding to Optimize Anticoagulation Strategy in Nonvalvular Atrial Fibrillation.","authors":"Yue Zhao, Li-Ya Cao, Ying-Xin Zhao, Di Zhao, Yi-Fan Huang, Fei Wang, Qian Wang","doi":"10.1055/a-2385-1452","DOIUrl":"10.1055/a-2385-1452","url":null,"abstract":"<p><strong>Background: </strong> Oral anticoagulation (OAC) following catheter ablation (CA) of nonvalvular atrial fibrillation (NVAF) is essential for the prevention of thrombosis events. Inappropriate application of OACs does not benefit stroke prevention but may be associated with a higher risk of bleeding. Therefore, this study aims to develop clinical data-driven machine learning (ML) methods to predict the risk of thrombosis and bleeding to establish more precise anticoagulation strategies for patients with NVAF.</p><p><strong>Methods: </strong> Patients with NVAF who underwent CA therapy were enrolled from <i>Southwest Hospital</i> from 2015 to 2023. This study compared eight ML algorithms to evaluate the predictive power for both thrombosis and bleeding. Model interpretations were recognized by feature importance and SHapley Additive exPlanations methods. With potential essential risk factors, simplified ML models were proposed to improve the feasibility of the tool.</p><p><strong>Results: </strong> A total of 1,055 participants were recruited, including 105 patients with thrombosis and 252 patients with bleeding. The models based on XGBoost achieved the best performance with accuracies of 0.740 and 0.781 for thrombosis and bleeding, respectively. Age, BNP, and the duration of heparin are closely related to the high risk of thrombosis, whereas the anticoagulation strategy, BNP, and lipids play a crucial role in the occurrence of bleeding. The optimized models enrolling crucial risk factors, RF-T for thrombosis and Xw-B for bleeding, achieved the best recalls of 0.774 and 0.780, respectively.</p><p><strong>Conclusion: </strong> The optimized models will have a great application potential in predicting thrombosis and bleeding among patients with NVAF and will form the basis for future score scales.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976639","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}
引用次数: 0
Unraveling the Molecular Pathogenesis of Protein C Deficiency-Associated VTE: Insights from Protein C Mutations C238G and R189W in Thai Patients. 揭示蛋白 C 缺乏症相关 VTE 的分子发病机制:泰国患者蛋白 C 突变 C238G 和 R189W 的启示。
IF 5 2区 医学
Thrombosis and haemostasis Pub Date : 2024-09-18 DOI: 10.1055/a-2408-9529
Pansakorn Tanratana, Karnsasin Seanoon, Panwajee Payongsri, Praguywan Kadegasem, Ampaiwan Chuansumrit, Nongnuch Sirachainan
{"title":"Unraveling the Molecular Pathogenesis of Protein C Deficiency-Associated VTE: Insights from Protein C Mutations C238G and R189W in Thai Patients.","authors":"Pansakorn Tanratana, Karnsasin Seanoon, Panwajee Payongsri, Praguywan Kadegasem, Ampaiwan Chuansumrit, Nongnuch Sirachainan","doi":"10.1055/a-2408-9529","DOIUrl":"10.1055/a-2408-9529","url":null,"abstract":"<p><strong>Background: </strong> Protein C (PC) deficiency is a well-established risk factor for thromboembolism (TE), commonly manifesting in pediatric patients. This study aimed to elucidate the pathogenic mechanisms of two novel PC mutations, C238G and R189W, identified in Thai children with both venous and arterial TE.</p><p><strong>Material and methods: </strong> The effects of wild-type (WT), C238G, and R189W PC variants were investigated through transient transfection of HEK293T cells. PC secretion levels were measured, and immunofluorescence analysis was performed to assess intracellular localization. ER stress-related gene expression and UPR activation were evaluated. Structural analysis was conducted to explore the significance of the C238 and R189W residue in PC functionality.</p><p><strong>Results: </strong> The C238G mutation led to a severe 95% reduction in PC secretion, while R189W showed a 30% decrease compared with WT. Immunofluorescence revealed that C238G-PC was predominantly retained in the ER, indicating protein misfolding. C238G-expressing cells exhibited significant upregulation of ER stress-related genes and UPR activation. In contrast, R189W resulted in only a modest increase in UPR gene expression, suggesting a less pronounced impact on protein folding and secretion. Structural analysis demonstrated the critical role of the C238 residue in maintaining PC's disulfide bond and overall conformation.</p><p><strong>Conclusion: </strong> This study reveals distinct molecular mechanisms by which the C238G and R189W mutations contribute to PC deficiency and increased thrombotic risk. The findings emphasize the essential role of the C238 residue in preserving PC structure and secretion, enhancing the understanding of PC deficiency-associated TE in pediatric patients.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126723","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}
引用次数: 0
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