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}
Pub Date : 2025-10-19DOI: 10.1016/j.thromres.2025.109515
Hong-Yan Li , Hai-Shan Wang , Jing Wang , Ya-Hong Wang , Shan-Ling Jiang , Li-Hong Wang
Background
This study assessed clinical practice guidelines (CPGs) for venous thromboembolism (VTE) prophylaxis and treatment in patients with stroke to provide evidence-based reference for clinicians.
Methods
We systematically identified CPGs published between January 1, 2020 and January 1, 2025. The Appraisal of Guidelines for Research & Evaluation II (AGREE II) and the Appraisal of Guidelines for Research and Evaluation-Recommendation Excellence (AGREE-REX) instruments were utilized to evaluate the quality of methodology and recommendations, respectively. Prophylaxis and treatment recommendations for VTE were extracted and compared for consistency and divergence.
Results
12 CPGs were included. The median (interquartile range [IQR]) scores for AGREE II six domains were: scope and purpose, 85.4 % (9.0 %); stakeholder involvement, 63.2 % (29.9 %); rigour of development, 65.4 % (18.5 %); clarity of presentation, 84.7 % (4.9 %); applicability, 49.5 % (33.3 %); and editorial independence, 76.0 % (41.7 %). The AGREE-REX assessment results were as follows: clinical applicability, 68.8 % (25.4 %); values and preferences, 19.3 % (20.6 %); and implementability, 36.5 % (9.4 %). Analysis of 64 key recommendations showed consistent support for intermittent pneumatic compression but not graduated compression stockings. Pharmacological prophylaxis remains controversial across both ischemic and hemorrhagic stroke.
Conclusion
Current stroke VTE guidelines demonstrate strengths in scope and clarity, but critical limitations in applicability and values and preferences. Although consensus on mechanical prophylaxis is clear, evidence for pharmacological prevention remains controversial. Future guideline development must enhance methodological rigour and address these critical evidence gaps through targeted primary research. This study provides a foundational synthesis of evidence-based insights to inform both clinical decision-making and the development of more applicable, trustworthy guidelines.
{"title":"Management of venous thromboembolism in stroke: A deep appraisal exposing discordance in guideline quality and recommendations","authors":"Hong-Yan Li , Hai-Shan Wang , Jing Wang , Ya-Hong Wang , Shan-Ling Jiang , Li-Hong Wang","doi":"10.1016/j.thromres.2025.109515","DOIUrl":"10.1016/j.thromres.2025.109515","url":null,"abstract":"<div><h3>Background</h3><div>This study assessed clinical practice guidelines (CPGs) for venous thromboembolism (VTE) prophylaxis and treatment in patients with stroke to provide evidence-based reference for clinicians.</div></div><div><h3>Methods</h3><div>We systematically identified CPGs published between January 1, 2020 and January 1, 2025. The Appraisal of Guidelines for Research & Evaluation II (AGREE II) and the Appraisal of Guidelines for Research and Evaluation-Recommendation Excellence (AGREE-REX) instruments were utilized to evaluate the quality of methodology and recommendations, respectively. Prophylaxis and treatment recommendations for VTE were extracted and compared for consistency and divergence.</div></div><div><h3>Results</h3><div>12 CPGs were included. The median (interquartile range [IQR]) scores for AGREE II six domains were: scope and purpose, 85.4 % (9.0 %); stakeholder involvement, 63.2 % (29.9 %); rigour of development, 65.4 % (18.5 %); clarity of presentation, 84.7 % (4.9 %); applicability, 49.5 % (33.3 %); and editorial independence, 76.0 % (41.7 %). The AGREE-REX assessment results were as follows: clinical applicability, 68.8 % (25.4 %); values and preferences, 19.3 % (20.6 %); and implementability, 36.5 % (9.4 %). Analysis of 64 key recommendations showed consistent support for intermittent pneumatic compression but not graduated compression stockings. Pharmacological prophylaxis remains controversial across both ischemic and hemorrhagic stroke.</div></div><div><h3>Conclusion</h3><div>Current stroke VTE guidelines demonstrate strengths in scope and clarity, but critical limitations in applicability and values and preferences. Although consensus on mechanical prophylaxis is clear, evidence for pharmacological prevention remains controversial. Future guideline development must enhance methodological rigour and address these critical evidence gaps through targeted primary research. This study provides a foundational synthesis of evidence-based insights to inform both clinical decision-making and the development of more applicable, trustworthy guidelines.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109515"},"PeriodicalIF":3.4,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145365127","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 : 2025-10-18DOI: 10.1016/j.thromres.2025.109517
Francesca Nencini , Enrico La Spina , Serena Borghi , Elvira Giurranna , Flavia Rita Argento , Eleonora Fini , Cesarina Giallongo , Andrea Duminuco , Giovanni Li Volti , Giuseppe Alberto Palumbo , Niccolò Taddei , Claudia Fiorillo , Daniele Tibullo , Matteo Becatti
Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by stem cell-derived clonal myeloproliferation, bone marrow fibrosis, extramedullary hematopoiesis and aberrant inflammation. About 90 % of MF patients carry mutations in JAK2, CALR, or MPL, with JAK2 mutations promoting cytokine independence, STAT proteins activation and enhances reactive oxygen species (ROS) production. Inflammation and oxidative stress are key contributors to thrombotic risk, a major cause of morbidity and mortality in MF. Fibrinogen, a key factor in coagulation and inflammation, may play a central role due to its susceptibility to oxidative modifications. In particular, in MPN patients, impaired fibrinolysis associated with endothelial cell dysfunction, increased ROS and proinflammatory cytokines production have been reported.
This study investigates the role of oxidation-induced structural and functional changes in fibrinogen in MF patients compared to healthy controls, also analyzing the effects of ruxolitinib, a first-in-class JAK inhibitor.
Plasma samples from 15 untreated MF patients, 39 ruxolitinib-treated MF patients, and 40 matched healthy controls were analyzed for redox status and fibrinogen properties.
MF patients showed elevated plasma lipid peroxidation and nitrate/nitrite levels, reduced antioxidant capacity, and lower free thiol content. These changes were associated with significant fibrinogen oxidation, leading to structural alterations and impaired function, including reduced fibrin polymerization and decreased plasmin-mediated fibrinolysis. Strong correlations were observed between oxidative stress markers and fibrinogen dysfunction. Treatment with ruxolitinib improved redox balance and restored fibrinogen structure and function.
These findings provide the first evidence of a prothrombotic profile in MF patients, driven by structural and functional fibrinogen modifications.
{"title":"Prothrombotic profiles in myelofibrosis: Fibrinogen oxidation and the beneficial effects of ruxolitinib","authors":"Francesca Nencini , Enrico La Spina , Serena Borghi , Elvira Giurranna , Flavia Rita Argento , Eleonora Fini , Cesarina Giallongo , Andrea Duminuco , Giovanni Li Volti , Giuseppe Alberto Palumbo , Niccolò Taddei , Claudia Fiorillo , Daniele Tibullo , Matteo Becatti","doi":"10.1016/j.thromres.2025.109517","DOIUrl":"10.1016/j.thromres.2025.109517","url":null,"abstract":"<div><div>Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by stem cell-derived clonal myeloproliferation, bone marrow fibrosis, extramedullary hematopoiesis and aberrant inflammation. About 90 % of MF patients carry mutations in JAK2, CALR, or MPL, with JAK2 mutations promoting cytokine independence, STAT proteins activation and enhances reactive oxygen species (ROS) production. Inflammation and oxidative stress are key contributors to thrombotic risk, a major cause of morbidity and mortality in MF. Fibrinogen, a key factor in coagulation and inflammation, may play a central role due to its susceptibility to oxidative modifications. In particular, in MPN patients, impaired fibrinolysis associated with endothelial cell dysfunction, increased ROS and proinflammatory cytokines production have been reported.</div><div>This study investigates the role of oxidation-induced structural and functional changes in fibrinogen in MF patients compared to healthy controls, also analyzing the effects of ruxolitinib, a first-in-class JAK inhibitor.</div><div>Plasma samples from 15 untreated MF patients, 39 ruxolitinib-treated MF patients, and 40 matched healthy controls were analyzed for redox status and fibrinogen properties.</div><div>MF patients showed elevated plasma lipid peroxidation and nitrate/nitrite levels, reduced antioxidant capacity, and lower free thiol content. These changes were associated with significant fibrinogen oxidation, leading to structural alterations and impaired function, including reduced fibrin polymerization and decreased plasmin-mediated fibrinolysis. Strong correlations were observed between oxidative stress markers and fibrinogen dysfunction. Treatment with ruxolitinib improved redox balance and restored fibrinogen structure and function.</div><div>These findings provide the first evidence of a prothrombotic profile in MF patients, driven by structural and functional fibrinogen modifications.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109517"},"PeriodicalIF":3.4,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145365128","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 : 2025-10-14DOI: 10.1016/j.thromres.2025.109505
Benjamin Crichi , Maxime Delrue , Tamim Alsuliman , Sylvain Le Jeune , Corinne Frere
{"title":"Reduced-dose versus full-dose apixaban for extended treatment of cancer-associated venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis","authors":"Benjamin Crichi , Maxime Delrue , Tamim Alsuliman , Sylvain Le Jeune , Corinne Frere","doi":"10.1016/j.thromres.2025.109505","DOIUrl":"10.1016/j.thromres.2025.109505","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"256 ","pages":"Article 109505"},"PeriodicalIF":3.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145327363","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}
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