Thrombosis research最新文献

{"title":"The effects of pseudoserum on thrombin-induced fibrin networks: Potential for clinical insight into coagulation independent of traditional parameters","authors":"Massimo Nunes ,&nbsp;Arneaux Kruger ,&nbsp;Burtram Fielding ,&nbsp;Douglas B. Kell ,&nbsp;Etheresia Pretorius","doi":"10.1016/j.thromres.2025.109530","DOIUrl":"10.1016/j.thromres.2025.109530","url":null,"abstract":"<div><div>Coagulation, although primarily regulated by platelets, endothelial cells, and clotting factors, can also be influenced by molecules that are not traditionally seen as related to coagulation, including cytokines, hormones, metabolites, reactive oxygen species, acute phase reactants, and more. Here, we derive pseudoserum or clotting factor-depleted fractions from control, type II diabetes mellitus, and Long COVID platelet-poor plasma (PPP) samples, and expose them to purified, exogenous fibrinogen obtained from healthy donors. Thrombin-induced fibrin networks were then formed and visualized using light and scanning electron microscopy. The results demonstrate that pseudoserum can greatly influence the organization, density, and ultrastructure of fibrin networks formed from purified fibrinogen, emphasizing the role of non-clotting factors in fibrin formation. Fibrin networks formed from purified fibrinogen exposed to control pseudoserum appear homogeneous, exhibiting organised architecture with few regions of unusual density or aggregates, whereas the networks formed using patient pseudoserum show disorganisation, regions of density, fibre-like strands, and anomalous aggregates. These abnormalities are also observed in patient PPP samples, suggesting that fibrin network characteristics in PPP samples are also significantly influenced by non-clotting factors and are somewhat independent of endogenous fibrinogen. Furthermore, fibrinolysis was significantly reduced in the patient groups, demonstrating the ability of pseudoserum to influence the susceptibility of fibrin networks to plasmin-induced degradation. The ability of pseudoserum to drive these changes, despite the essential absence of endogenous fibrinogen and other classical clotting factors, suggests that soluble molecules retained in pseudoserum can directly modify fibrinogen's structural conformation and functionality, influence thrombin-mediated fibrin formation and polymerization, and/or impact Factor XIII's crosslinking capabilities. This study provides a systems-level perspective on the influence of pseudoserum on fibrin networks and highlights the potential of serum and other clotting factor–depleted fractions to yield deeper mechanistic and diagnostic insights into coagulation.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109530"},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514016","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":"Association of anticoagulant therapy with bleeding in patients with chronic liver disease: A case-cross over study using the National Veterans Health Administration database","authors":"Amir Mahmoud ,&nbsp;Kristen M. Sanfilippo ,&nbsp;Brian F. Gage ,&nbsp;Suhong Luo ,&nbsp;Amber Afzal","doi":"10.1016/j.thromres.2025.109529","DOIUrl":"10.1016/j.thromres.2025.109529","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109529"},"PeriodicalIF":3.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496789","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":"Venous thrombosis in lung cancer compared with other tumors: results from the TESEO-SEOM registry","authors":"Claudia Iglesias-Perez ,&nbsp;Paula Jimenez-Fonseca ,&nbsp;Javier López Robles ,&nbsp;Silvia García Adrián ,&nbsp;Isaura Fernández Pérez ,&nbsp;Purificación Martínez del Prado ,&nbsp;Jaime Rubio Pérez ,&nbsp;Eva Martínez de Castro ,&nbsp;Carmen Díaz Pedroche ,&nbsp;Marta García de Herreros ,&nbsp;Marta Carmona Campos ,&nbsp;Ana Belén Rupérez Blanco ,&nbsp;Mercedes Salgado Fernández ,&nbsp;Teresa Quintanar Verdúguez ,&nbsp;David Marrupe González ,&nbsp;Marta Covela Rúa ,&nbsp;Jose Antonio Santiago Crespo ,&nbsp;María Nieva Muñoz ,&nbsp;Andrés Muñoz ,&nbsp;Alberto Carmona-Bayonas","doi":"10.1016/j.thromres.2025.109525","DOIUrl":"10.1016/j.thromres.2025.109525","url":null,"abstract":"<div><h3>Background</h3><div>Cancer-associated venous thromboembolism (VTE) is a major adverse prognostic factor with heterogeneous outcomes across tumor types. We aimed to describe the characteristics of lung cancer patients with VTE, compare outcomes across malignancies, and assess their association with complications, progression, and survival.</div></div><div><h3>Methods</h3><div>We analyzed TESEO-SEOM, a prospective multicenter registry including patients with active cancer and VTE. Patients were stratified by tumor site, with lung as reference. Outcomes included recurrent VTE, bleeding, and survival. Analyses were stratified by tumor type and VTE presentation (clinically suspected, symptomatic/asymptomatic incidental). Complications were estimated using competing-risk methods.</div></div><div><h3>Results</h3><div>Among 3855 patients, the most frequent cancers were gastrointestinal (39.4 %), lung (22.2 %), and breast (10.4 %). Pulmonary embolism predominated (55 %), especially in lung cancer (69.8 %). Overall, 48.9 % of events were clinically suspected and 50.9 % incidental; suspected were more common in lung cancer (53.9 %), whereas incidental diagnoses predominated in gastrointestinal tumors (58.8 %).</div><div>Complications occurred in 17.6 % (10.2 % bleeding, 7.4 % recurrent VTE). Recurrence was highest in gastrointestinal cancers (11.4 %, Gray's <em>p</em> = 0.022), while bleeding did not differ (<em>p</em> = 0.213). VTE-related mortality was low (1 %), while mixed-cause mortality was highest in lung cancer (17.2 %). Median PFS and OS were shortest in lung cancer (4.5 and 7.7 months, <em>p</em> &lt; 0.0001). Incidental asymptomatic events conferred longer survival, particularly in lung cancer (OS 11.5 vs. 7.3 months for symptomatic incidental and 5.6 for suspected, <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>VTE in lung cancer is associated with more severe presentation, higher mixed-cause mortality, and worse survival than in other tumors. Incidental asymptomatic VTE predicts better outcomes, supporting risk stratification by tumor type and presentation.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109525"},"PeriodicalIF":3.4,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517380","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":"Bone marrow blasts- and modified EASIX-guided risk stratification for coagulopathy and outcomes after CAR-T therapy in relapsed/refractory B-ALL","authors":"Yingying Li ,&nbsp;Jiachen Liu ,&nbsp;Lili Luo ,&nbsp;Lijuan Zhou ,&nbsp;Zhong Wu ,&nbsp;Wei Sang ,&nbsp;Huiwen Jiang ,&nbsp;Jingming Wang ,&nbsp;Xindi Wang ,&nbsp;Peiru Li ,&nbsp;Zhaozhao Chen ,&nbsp;Jinhui Shu ,&nbsp;Wenjing Luo ,&nbsp;Yu Hu ,&nbsp;Yuhua Li ,&nbsp;Heng Mei","doi":"10.1016/j.thromres.2025.109527","DOIUrl":"10.1016/j.thromres.2025.109527","url":null,"abstract":"<div><h3>Background</h3><div>Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). While CAR-T-associated coagulopathy (CARAC) remains a critical complication, significantly increasing the risk of hemorrhage and disseminated intravascular coagulation (DIC).</div></div><div><h3>Aims</h3><div>To develop an effective CARAC risk stratification and outcome prediction model.</div></div><div><h3>Methods</h3><div>This multicenter retrospective study enrolled r/r B-ALL patients who received CD19 CAR-T therapy between January 2016 and July 2025. Machine learning, logistic regression and cutoff values were utilized to select key variables and develop predictive models. Model performance and clinical applicability were evaluated by receiver operating characteristic, calibration, and clinical decision curves. Survival analyses evaluated the impact of CARAC severity on overall survival (OS) and progression-free survival (PFS) and to validate the prognostic value of the prediction model.</div></div><div><h3>Results</h3><div>Bone marrow (BM) blasts and the modified endothelial activation and stress index (mEASIX) were independent predictors for CARAC. Patients with mEASIX&lt;4.0 were identified as low-risk CARAC. For patients with mEASIX≥4.0, CARAC was stratified by BM blast percentage (blast%). Blast% between 10 % and 44 % indicated high-risk CARAC-nonDIC, and a blast% ≥ 44 % indicated high-risk CARAC-DIC. Moreover, compared to non-CARAC patients, CARAC patients had inferior OS (hazard ratio [HR]: 2.62, <em>p</em> = 0.002) and PFS (HR: 2.11, p = 0.002). The stratified prediction model revealed progressively worse OS and PFS from low-risk CARAC patients to high-risk CARAC-nonDIC, with high-risk CARAC-DIC patients demonstrating the most unfavorable outcomes.</div></div><div><h3>Conclusions</h3><div>An effective CARAC risk prediction and stratification model was established. High-risk CARAC patients, particularly CARAC-DIC, were associated with significantly worse outcomes.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109527"},"PeriodicalIF":3.4,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496851","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":"A novel F7 mutation (p.Gly217Arg) associated with infantile intracranial hemorrhage successfully managed with rFVIIa","authors":"Mustafa Ozay ,&nbsp;Ugur Gumus ,&nbsp;Ekrem Ünal","doi":"10.1016/j.thromres.2025.109526","DOIUrl":"10.1016/j.thromres.2025.109526","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109526"},"PeriodicalIF":3.4,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466910","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":"The Chinese Haemophilia Individualized Prophylaxis (CHIPS): A cost-effective regimen for zero joint bleeding and long-term joint health in boys with Severe Haemophilia A (SHA) on factor replacement","authors":"Wanru Yao ,&nbsp;Di Ai ,&nbsp;Qing Zhang ,&nbsp;Xiaojing Li ,&nbsp;Min Zhou ,&nbsp;Ningning Zhang ,&nbsp;Yan Wang ,&nbsp;Sheng Yang ,&nbsp;Zhenping Chen ,&nbsp;Gang Li ,&nbsp;Koon-Hung Luke ,&nbsp;Runhui Wu","doi":"10.1016/j.thromres.2025.109528","DOIUrl":"10.1016/j.thromres.2025.109528","url":null,"abstract":"<div><div>The management of severe haemophilia A (SHA) in China has evolved significantly from on-demand treatment to low-dose prophylaxis, substantially reducing bleeding rates. The Chinese Haemophilia Individualized Prophylaxis Study (CHIPS) protocol was developed as a standardized, cost-effective framework to pursue zero joint bleeding and long-term joint health preservation. This review provides a comprehensive overview of the CHIPS protocol, synthesizing evidence from three interrelated studies that demonstrate the efficacy of a structured, individualized approach incorporating pharmacokinetic-guided dosing and multimodal joint assessment. The results indicate that this strategy achieves near-zero bleeding rates, improves quality of life, and maintains joint health while optimizing factor consumption. Furthermore, the review discusses the expanding role of the CHIPS framework in the current treatment landscape, highlighting its utility as a practical platform for monitoring patients transitioning to non-factor therapies, such as emicizumab, in resource-conscious settings. The CHIPS protocol represents a timely and scalable prophylaxis framework that optimizes factor replacement therapy and adapts to novel agents. Its structured monitoring and individualized dosing offer a critical solution for protecting joint health in boys with SHA until non-factor and gene therapies become widely accessible in China<strong>.</strong></div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109528"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517455","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":"In vitro anticoagulant effect of nafamostat mesylate in andexanet-induced heparin resistance","authors":"Hisako Okada ,&nbsp;Yuko Mishima ,&nbsp;Sharon M. Bouvette ,&nbsp;Min U.K. Jang ,&nbsp;Kenichi A. Tanaka ,&nbsp;Amir L. Butt","doi":"10.1016/j.thromres.2025.109524","DOIUrl":"10.1016/j.thromres.2025.109524","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109524"},"PeriodicalIF":3.4,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466909","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":"Contemporary reperfusion therapies in patients with intermediate- and high-risk pulmonary embolism","authors":"Burton H. Shen ,&nbsp;Divya A. Shankar ,&nbsp;Nicholas A. Bosch ,&nbsp;Allan J. Walkey ,&nbsp;Gregory Piazza ,&nbsp;Elizabeth S. Klings ,&nbsp;Anica C. Law","doi":"10.1016/j.thromres.2025.109523","DOIUrl":"10.1016/j.thromres.2025.109523","url":null,"abstract":"<div><h3>Background</h3><div>Without clear guidelines, contemporary use of reperfusion therapy for intermediate-risk and high-risk pulmonary embolism (PE) may vary widely. We assessed variation and trends in use of reperfusion therapies (systemic thrombolysis, catheter-directed thrombolysis, mechanical thrombectomy) and how practices change when hospitals adopt mechanical thrombectomy.</div></div><div><h3>Methods</h3><div>Using the national Premier Inc. AI Database (2016–2022), we identified adults with intermediate-risk or high-risk PE. For each reperfusion therapy, our primary outcome was intraclass correlation coefficient (ICC, representing between-hospital variation unexplained by patient/hospital characteristics; <em>a priori</em>, ICC &gt; 15 % deemed “high” variation) and proportion trends over time with hierarchical regression models and assessed trends in use. Among hospitals that adopted mechanical thrombectomy, we conducted interrupted time series analysis to assess changes in use of systemic thrombolysis, catheter-directed thrombolysis, and any reperfusion therapy.</div></div><div><h3>Results</h3><div>We assessed 13,777 patients (11,846 intermediate-risk; 1931 high-risk PE) admitted in the US between 2016 and 2022. High variation was observed in catheter-directed thrombolysis (intermediate-risk: ICC 23.1 %; high-risk: ICC 23.8 %) and thrombectomy use (intermediate-risk: ICC 35.4 %; high-risk: ICC 25.1 %). Mechanical thrombectomy use increased from 0.6 % to 14.3 % between 2016 and 2022 (<em>p</em> &lt; 0.001). Hospital adoption of mechanical thrombectomy was associated with a deceleration in growth of catheter-directed thrombolysis rates.</div></div><div><h3>Conclusions</h3><div>Among patients with intermediate-risk and high-risk PE in the US, reperfusion therapy use varies widely, and the use of mechanical thrombectomy increased between 2016 and 2022. At hospitals adopting mechanical thrombectomy, thrombectomy supplants catheter-directed thrombolysis without increasing total use of reperfusion therapy. These results raise questions about standardization of care, optimal resource allocation, and impact on patient outcomes.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109523"},"PeriodicalIF":3.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419434","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":"Predictive value of the systemic immuane-inflammation index for deep vein thrombosis: A meta-analysis","authors":"Xiaoxiao Chen ,&nbsp;Yuntao Mao ,&nbsp;Yuxin Ge ,&nbsp;Dandan Ju","doi":"10.1016/j.thromres.2025.109522","DOIUrl":"10.1016/j.thromres.2025.109522","url":null,"abstract":"<div><h3>Objective</h3><div>The systemic immune-inflammation index (SII), a new inflammatory marker, is considered a predictive indicator for multiple malignant tumors and inflammatory illnesses. Its relationship with deep vein thrombosis (DVT) has garnered growing attention. This research seeks to systematically examine the relationship between SII and DVT.</div></div><div><h3>Methods</h3><div>Embase, Web of Science, Cochrane Library, and PubMed were searched up to January 6, 2025, for observational studies examining the link between SII and DVT. Two reviewers separately screened the retrieved articles, extracted data, and appraised the quality of the enrolled studies. MetaDisc version 1.4 and StataMP 15 were utilized to carry out statistical analyses.</div></div><div><h3>Results</h3><div>14 studies involving 13,655 individuals were included. The meta-analysis demonstrated that individuals with DVT exhibited elevated SII in comparison to those without DVT (WMD = 938.60; 95 % CI: 466.55–1410.64; <em>p</em> &lt; 0.001). Moreover, individuals with elevated SII had a 4.73-fold greater risk of DVT than those with low SII (95 % CI: 2.19–10.19; <em>p</em> &lt; 0.001). The pooled diagnostic performance revealed a specificity of 78 % (95 % CI: 71 %–84 %), sensitivity of 69 % (95 % CI: 56 %–79 %), negative likelihood ratio of 0.40 (95 % CI: 0.26–0.60), positive likelihood ratio of 3.18 (95 % CI: 2.12–4.76), and diagnostic odds ratio of 7.96 (95 % CI: 3.66–17.30). The area under the receiver operating characteristic curve was 0.81 (95 % CI: 0.77–0.84). Sensitivity analyses were carried out by sequentially excluding individual studies, and no substantial changes were observed in the mean differences, odds ratios, or diagnostic estimates, indicating the stability of the results. No substantial publication bias was detected in the analyses of mean differences, odds ratios, or diagnostic measures.</div></div><div><h3>Conclusion</h3><div>Elevated SII is related to a higher likelihood of DVT, suggesting its potential as a valuable predictor of DVT risk.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109522"},"PeriodicalIF":3.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419432","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":"Three new variants of the fibrinogen-related domain of the fibrinogen Bβ chain","authors":"Roman Kotlín ,&nbsp;Žofie Sovová ,&nbsp;Tereza Sklenářová ,&nbsp;Marek Havlíček ,&nbsp;Jiří Suttnar ,&nbsp;Leona Chrastinová ,&nbsp;Ingrid Hrachovinová ,&nbsp;Alžběta Hlaváčková","doi":"10.1016/j.thromres.2025.109521","DOIUrl":"10.1016/j.thromres.2025.109521","url":null,"abstract":"<div><h3>Introduction</h3><div>Variants in genes coding fibrinogen chains may lead to a quantitative fibrinogen disorder—hypofibrinogenemia. The aim of the study was to determine the cause of congenital hypofibrinogenemia and characterize the underlying structure and function of fibrinogen.</div></div><div><h3>Methods</h3><div>Genetic and proteomic analyses were performed to determine fibrinogen variants and detect their presence in plasma. Scanning electron microscopy was used to study fibrin clot morphology, and polymerization experiments were used to determine its effect on fibrin formation. Bioinformatics and <em>in silico</em> structural biology techniques were used to predict the impact of variant on the protein's stability and function.</div></div><div><h3>Results</h3><div>We identified three previously undescribed variants of the fibrinogen-related domain (FReD) of the fibrinogen Bβ chain—<em>FGB</em>:p.Asp350His, <em>FGB</em>:p.Arg436Lys, and <em>FGB</em>:p.Tyr447Cys. Fibrin structure and fibrin polymerization were very slightly affected in <em>FGB</em>:p.Asp350His and <em>FGB</em>: p.Arg436Lys cases. The <em>FGB</em>:p.Tyr447Cys variant could have physiological manifestations because it destabilizes the binding site of the fibrinogen Bβ chain. The <em>FGB</em>:Arg436Lys variant does not destabilize the protein's structure, but it may disturb fibrin polymerization. High conservation of Arg436 may indicate its importance in fibrinogen biosynthesis or secretion. <em>FGB</em>:p.Asp350His is situated in the N-terminal residue of the third β-strand of the central antiparallel β-sheet of the FReD, forming a hydrogen bond with Asp346, and Asp350 seems to have a negligible effect on the formation of the correct Bβ chain structure.</div></div><div><h3>Conclusion</h3><div>The analyzed variants in the FReD of the fibrinogen Bβ chain seems to have an impact on the proper structure of the fibrinogen-related domain of the fibrinogen Bβ chain.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109521"},"PeriodicalIF":3.4,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419431","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}