Pub Date : 2025-11-03DOI: 10.1016/j.thromres.2025.109525
Claudia Iglesias-Perez , Paula Jimenez-Fonseca , Javier López Robles , Silvia García Adrián , Isaura Fernández Pérez , Purificación Martínez del Prado , Jaime Rubio Pérez , Eva Martínez de Castro , Carmen Díaz Pedroche , Marta García de Herreros , Marta Carmona Campos , Ana Belén Rupérez Blanco , Mercedes Salgado Fernández , Teresa Quintanar Verdúguez , David Marrupe González , Marta Covela Rúa , Jose Antonio Santiago Crespo , María Nieva Muñoz , Andrés Muñoz , Alberto Carmona-Bayonas
Background
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.
Methods
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.
Results
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 %).
Complications occurred in 17.6 % (10.2 % bleeding, 7.4 % recurrent VTE). Recurrence was highest in gastrointestinal cancers (11.4 %, Gray's p = 0.022), while bleeding did not differ (p = 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, p < 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, p < 0.001).
Conclusion
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.
癌症相关静脉血栓栓塞(VTE)是一种主要的不良预后因素,不同肿瘤类型的预后不尽相同。我们的目的是描述肺癌静脉血栓栓塞患者的特征,比较不同恶性肿瘤的预后,并评估其与并发症、进展和生存的关系。方法我们分析了TESEO-SEOM,一项前瞻性多中心登记,包括活动性癌症和静脉血栓栓塞患者。按肿瘤部位分层,以肺为参照。结果包括静脉血栓栓塞复发、出血和生存。根据肿瘤类型和静脉血栓栓塞表现(临床怀疑、有症状/无症状偶发)对分析进行分层。采用竞争风险法估计并发症。结果3855例患者中,最常见的肿瘤为胃肠道(39.4%)、肺癌(22.2%)和乳腺癌(10.4%)。肺栓塞占多数(55%),尤其是肺癌(69.8%)。总体而言,48.9%的事件为临床怀疑,50.9%为偶然事件;疑似多见于肺癌(53.9%),而偶然诊断主要见于胃肠道肿瘤(58.8%)。并发症发生率为17.6%(10.2%出血,7.4%静脉血栓栓塞复发)。胃肠道肿瘤复发率最高(11.4%,Gray’s p = 0.022),而出血无差异(p = 0.213)。静脉血栓栓塞相关死亡率较低(1%),而肺癌的混合原因死亡率最高(17.2%)。肺癌患者的中位PFS和OS最短(4.5个月和7.7个月,p < 0.0001)。偶发无症状事件可延长生存期,尤其是肺癌患者(偶发症状患者生存期11.5个月,疑似患者生存期7.3个月,p < 0.001)。结论与其他肿瘤相比,vte在肺癌中的表现更严重,混合原因死亡率更高,生存期更差。偶发无症状静脉血栓栓塞预测更好的预后,支持肿瘤类型和表现的风险分层。
{"title":"Venous thrombosis in lung cancer compared with other tumors: results from the TESEO-SEOM registry","authors":"Claudia Iglesias-Perez , Paula Jimenez-Fonseca , Javier López Robles , Silvia García Adrián , Isaura Fernández Pérez , Purificación Martínez del Prado , Jaime Rubio Pérez , Eva Martínez de Castro , Carmen Díaz Pedroche , Marta García de Herreros , Marta Carmona Campos , Ana Belén Rupérez Blanco , Mercedes Salgado Fernández , Teresa Quintanar Verdúguez , David Marrupe González , Marta Covela Rúa , Jose Antonio Santiago Crespo , María Nieva Muñoz , Andrés Muñoz , 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> < 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> < 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}
Pub Date : 2025-11-03DOI: 10.1016/j.thromres.2025.109527
Yingying Li , Jiachen Liu , Lili Luo , Lijuan Zhou , Zhong Wu , Wei Sang , Huiwen Jiang , Jingming Wang , Xindi Wang , Peiru Li , Zhaozhao Chen , Jinhui Shu , Wenjing Luo , Yu Hu , Yuhua Li , Heng Mei
Background
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).
Aims
To develop an effective CARAC risk stratification and outcome prediction model.
Methods
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.
Results
Bone marrow (BM) blasts and the modified endothelial activation and stress index (mEASIX) were independent predictors for CARAC. Patients with mEASIX<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, p = 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.
Conclusions
An effective CARAC risk prediction and stratification model was established. High-risk CARAC patients, particularly CARAC-DIC, were associated with significantly worse outcomes.
{"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 , Jiachen Liu , Lili Luo , Lijuan Zhou , Zhong Wu , Wei Sang , Huiwen Jiang , Jingming Wang , Xindi Wang , Peiru Li , Zhaozhao Chen , Jinhui Shu , Wenjing Luo , Yu Hu , Yuhua Li , 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<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}
Pub Date : 2025-11-01DOI: 10.1016/j.thromres.2025.109528
Wanru Yao , Di Ai , Qing Zhang , Xiaojing Li , Min Zhou , Ningning Zhang , Yan Wang , Sheng Yang , Zhenping Chen , Gang Li , Koon-Hung Luke , Runhui Wu
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.
{"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 , Di Ai , Qing Zhang , Xiaojing Li , Min Zhou , Ningning Zhang , Yan Wang , Sheng Yang , Zhenping Chen , Gang Li , Koon-Hung Luke , 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}
Pub Date : 2025-10-30DOI: 10.1016/j.thromres.2025.109524
Hisako Okada , Yuko Mishima , Sharon M. Bouvette , Min U.K. Jang , Kenichi A. Tanaka , Amir L. Butt
{"title":"In vitro anticoagulant effect of nafamostat mesylate in andexanet-induced heparin resistance","authors":"Hisako Okada , Yuko Mishima , Sharon M. Bouvette , Min U.K. Jang , Kenichi A. Tanaka , 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}
Pub Date : 2025-10-27DOI: 10.1016/j.thromres.2025.109523
Burton H. Shen , Divya A. Shankar , Nicholas A. Bosch , Allan J. Walkey , Gregory Piazza , Elizabeth S. Klings , Anica C. Law
Background
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.
Methods
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; a priori, ICC > 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.
Results
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 (p < 0.001). Hospital adoption of mechanical thrombectomy was associated with a deceleration in growth of catheter-directed thrombolysis rates.
Conclusions
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.
{"title":"Contemporary reperfusion therapies in patients with intermediate- and high-risk pulmonary embolism","authors":"Burton H. Shen , Divya A. Shankar , Nicholas A. Bosch , Allan J. Walkey , Gregory Piazza , Elizabeth S. Klings , 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 > 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> < 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}
Pub Date : 2025-10-27DOI: 10.1016/j.thromres.2025.109522
Xiaoxiao Chen , Yuntao Mao , Yuxin Ge , Dandan Ju
Objective
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.
Methods
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.
Results
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; p < 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; p < 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.
Conclusion
Elevated SII is related to a higher likelihood of DVT, suggesting its potential as a valuable predictor of DVT risk.
{"title":"Predictive value of the systemic immuane-inflammation index for deep vein thrombosis: A meta-analysis","authors":"Xiaoxiao Chen , Yuntao Mao , Yuxin Ge , 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> < 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> < 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}
Pub Date : 2025-10-24DOI: 10.1016/j.thromres.2025.109521
Roman Kotlín , Žofie Sovová , Tereza Sklenářová , Marek Havlíček , Jiří Suttnar , Leona Chrastinová , Ingrid Hrachovinová , Alžběta Hlaváčková
Introduction
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.
Methods
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 in silico structural biology techniques were used to predict the impact of variant on the protein's stability and function.
Results
We identified three previously undescribed variants of the fibrinogen-related domain (FReD) of the fibrinogen Bβ chain—FGB:p.Asp350His, FGB:p.Arg436Lys, and FGB:p.Tyr447Cys. Fibrin structure and fibrin polymerization were very slightly affected in FGB:p.Asp350His and FGB: p.Arg436Lys cases. The FGB:p.Tyr447Cys variant could have physiological manifestations because it destabilizes the binding site of the fibrinogen Bβ chain. The FGB: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. FGB: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.
Conclusion
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.
{"title":"Three new variants of the fibrinogen-related domain of the fibrinogen Bβ chain","authors":"Roman Kotlín , Žofie Sovová , Tereza Sklenářová , Marek Havlíček , Jiří Suttnar , Leona Chrastinová , Ingrid Hrachovinová , 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}
Pub Date : 2025-10-20DOI: 10.1016/j.thromres.2025.109518
Oliver Buchhave Pedersen , Erik Lerkevang Grove , Steen Dalby Kristensen , Leonardo Pasalic , Anne-Mette Hvas , Peter H. Nissen
Background
Reduced effect of antiplatelet therapy has been observed in patients with ST-segment elevation myocardial infarction (STEMI). MicroRNA (miR) expression may serve as biomarkers for platelet function and the effect of antiplatelet therapy.
Aim
In acute STEMI patients, we investigated changes in miR expression from the acute event to a more stable phase, and evaluated their association with platelet function at both time points to assess their potential as biomarkers of antiplatelet therapy efficacy.
Methods
Patients admitted with acute STEMI for primary percutaneous coronary intervention were included and treated according to guidelines. Samples were collected within 24 h after admission and at 2–3 months after enrolment. Expression of candidate miRs, platelet reactivity markers evaluated by flow cytometry, platelet impedance aggregometry and serum thromboxane B2 were measured at both time points.
Results
Samples were obtained in 44 STEMI patients. Two miRs (miR-15a-5p and miR-21-5p) showed lower, whereas five (miR-26b-5p, miR-126-3p, miR-150-5p, miR-223-3p and miR-423-5p) showed higher expression at follow-up than at baseline. At baseline, miR-26b-5p expression consistently correlated with the expression of the fibrinogen receptor on activated platelets, across different agonists (rho: from 0.29 to 0.32, p < 0.05). At follow-up, miR-93-5p expression was associated with platelet aggregation using various agonists (rho: from −0.39 to −0.47, p < 0.02).
Conclusions
Seven miRs were differentially expressed at follow-up compared to baseline. Several miRs were linked to platelet function at baseline and follow-up, suggesting that a single miR may not be sufficient as a biomarker for platelet function and the effect of antiplatelet therapy.
{"title":"MicroRNA dynamics and their link to platelet function following acute ST-segment elevation myocardial infarction","authors":"Oliver Buchhave Pedersen , Erik Lerkevang Grove , Steen Dalby Kristensen , Leonardo Pasalic , Anne-Mette Hvas , Peter H. Nissen","doi":"10.1016/j.thromres.2025.109518","DOIUrl":"10.1016/j.thromres.2025.109518","url":null,"abstract":"<div><h3>Background</h3><div>Reduced effect of antiplatelet therapy has been observed in patients with ST-segment elevation myocardial infarction (STEMI). MicroRNA (miR) expression may serve as biomarkers for platelet function and the effect of antiplatelet therapy.</div></div><div><h3>Aim</h3><div>In acute STEMI patients, we investigated changes in miR expression from the acute event to a more stable phase, and evaluated their association with platelet function at both time points to assess their potential as biomarkers of antiplatelet therapy efficacy.</div></div><div><h3>Methods</h3><div>Patients admitted with acute STEMI for primary percutaneous coronary intervention were included and treated according to guidelines. Samples were collected within 24 h after admission and at 2–3 months after enrolment. Expression of candidate miRs, platelet reactivity markers evaluated by flow cytometry, platelet impedance aggregometry and serum thromboxane B<sub>2</sub> were measured at both time points.</div></div><div><h3>Results</h3><div>Samples were obtained in 44 STEMI patients. Two miRs (miR-15a-5p and miR-21-5p) showed lower, whereas five (miR-26b-5p, miR-126-3p, miR-150-5p, miR-223-3p and miR-423-5p) showed higher expression at follow-up than at baseline. At baseline, miR-26b-5p expression consistently correlated with the expression of the fibrinogen receptor on activated platelets, across different agonists (rho: from 0.29 to 0.32, <em>p</em> < 0.05). At follow-up, miR-93-5p expression was associated with platelet aggregation using various agonists (rho: from −0.39 to −0.47, <em>p</em> < 0.02).</div></div><div><h3>Conclusions</h3><div>Seven miRs were differentially expressed at follow-up compared to baseline. Several miRs were linked to platelet function at baseline and follow-up, suggesting that a single miR may not be sufficient as a biomarker for platelet function and the effect of antiplatelet therapy.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109518"},"PeriodicalIF":3.4,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356313","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}
Pub Date : 2025-10-20DOI: 10.1016/j.thromres.2025.109516
Juliette Hugueny , Anna de Ricolfis , Nicolaï Johnson , Nathalie Chabbert-Buffet , Sarra Cristofari
Objective
This review aimed to synthesize recent data on venous thromboembolism (VTE) risk in the context of masculinizing hormone therapy with testosterone.
Methods
An electronic search was performed in MEDLINE/PubMed without date restrictions. Eligible articles were peer-reviewed observational and interventional studies and had to be written in English. Results are presented by theme of analysis.
Results
Most recent large-scale studies investigating trans masculine populations have not found a statistically significant change in the risk of VTE. However, most of the available data relate to younger individuals with minimal cardiovascular risk factors. For patients with a personal or family history of VTE, the introduction of testosterone therapy should be discussed within a multidisciplinary team specializing in transgender health, balancing the risk-benefit ratio in a population where the risk of suicide is high and is largely reduced by gender-affirming hormone therapy.
Conclusions
Most of the studies did not found a significant change in the risk of venous thromboembolism in trans masculine persons taking testosterone. However, data are limited, and further robust studies are warranted to clarify these data and to generalize these results to higher veinous thromboembolic risk groups.
{"title":"Assessing the risk of venous thromboembolism in trans masculine persons on gender-affirming hormone therapy: A literature review","authors":"Juliette Hugueny , Anna de Ricolfis , Nicolaï Johnson , Nathalie Chabbert-Buffet , Sarra Cristofari","doi":"10.1016/j.thromres.2025.109516","DOIUrl":"10.1016/j.thromres.2025.109516","url":null,"abstract":"<div><h3>Objective</h3><div>This review aimed to synthesize recent data on venous thromboembolism (VTE) risk in the context of masculinizing hormone therapy with testosterone.</div></div><div><h3>Methods</h3><div>An electronic search was performed in MEDLINE/PubMed without date restrictions. Eligible articles were peer-reviewed observational and interventional studies and had to be written in English. Results are presented by theme of analysis.</div></div><div><h3>Results</h3><div>Most recent large-scale studies investigating trans masculine populations have not found a statistically significant change in the risk of VTE. However, most of the available data relate to younger individuals with minimal cardiovascular risk factors. For patients with a personal or family history of VTE, the introduction of testosterone therapy should be discussed within a multidisciplinary team specializing in transgender health, balancing the risk-benefit ratio in a population where the risk of suicide is high and is largely reduced by gender-affirming hormone therapy.</div></div><div><h3>Conclusions</h3><div>Most of the studies did not found a significant change in the risk of venous thromboembolism in trans masculine persons taking testosterone. However, data are limited, and further robust studies are warranted to clarify these data and to generalize these results to higher veinous thromboembolic risk groups.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109516"},"PeriodicalIF":3.4,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145365189","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}