{"title":"Increased contact system activity three months after starting combined oral contraceptives.","authors":"Jesper Strandberg, Jette Nybo, Inger Lise Gade, Yaseelan Palarasah, Else-Marie Bladbjerg, Søren Risom Kristensen","doi":"10.1016/j.thromres.2025.109428","DOIUrl":"10.1016/j.thromres.2025.109428","url":null,"abstract":"<p><strong>Introduction: </strong>Combined oral contraceptives (COC) are associated with an increased risk of venous thromboembolism (VTE). The contact system (CAS) can, when activated, stimulate coagulation, and may play a role in thrombus formation. Our recent case-control study showed increased CAS capacity and in vivo activity in COC users, indicating a systemic activation that could contribute to VTE risk during COC treatment. Aim This study investigates intraindividual changes in CAS in women before and after start of COC treatment.</p><p><strong>Materials and methods: </strong>Twenty-four women aged between 15 and 34 years, who were starting treatment with COC, were included in the study. A baseline blood sample was drawn before start of COC, and a follow-up blood sample 3-4 months later. The capacity and activity of CAS, i.e. factor XII (FXII), prekallikrein (PK), H-kininogen (HK), C1-esterase inhibitor (C1inh), cleaved HK (cHK) and endogenous kallikrein potential (EKP), were analyzed.</p><p><strong>Results: </strong>Our study showed significantly increased levels of FXII (median 29.4 vs 42.9 mg/L; p < 0.0001) and decreased levels of C1inh (0.21 vs 0.20 g/L; p = 0.005). Increased EKP (1859 vs 2203 nmol/L*min; p = 0.0004) demonstrated an increased capacity of CAS, and increased levels of cHK (0.70 vs 0.96 μg/L; p < 0.0001) indicated an increased activity of CAS in vivo. The levels of PK and HK showed no significant changes.</p><p><strong>Conclusion: </strong>This study demonstrates an increased intraindividual CAS capacity as well as an increased CAS activity during treatment with COC supporting the previous research. These effects on CAS may contribute to the increased thrombotic risk caused by COC.</p>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"253 ","pages":"109428"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817455","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}
Jose Pardos-Gea , Jordi Barquinero , Iñaki Alvarez , Vicente Cortina , Iris Garcia Martínez , Laura Martín Fernández , Francisco Vidal
{"title":"A comprehensive review of the autoimmune pathogenesis of acquired hemophilia A","authors":"Jose Pardos-Gea , Jordi Barquinero , Iñaki Alvarez , Vicente Cortina , Iris Garcia Martínez , Laura Martín Fernández , Francisco Vidal","doi":"10.1016/j.thromres.2025.109444","DOIUrl":"10.1016/j.thromres.2025.109444","url":null,"abstract":"<div><div>Acquired haemophilia A (AHA) constitutes the most frequent form of autoimmunity againts coagulation factors. The pathogenic basis of anti-FVIII autoantibodies production remains unknown and our narrative review explores the possible causes and provides an overview of evidence data.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109444"},"PeriodicalIF":3.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917652","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}
Vanessa L. Gauvin , Marie-France N. Soucy , Jaël D. Richard , Kate A. Graham , Alexis J. Matthew , Mathieu P.A. Hébert , Jérémie A. Doiron , Mathieu Johnson , Eric P. Allain , David A. Barnett , Sandra Turcotte , Luc H. Boudreau
{"title":"The role of 12-lipoxygenase in regulating megakaryocyte maturation and platelet-like particles production","authors":"Vanessa L. Gauvin , Marie-France N. Soucy , Jaël D. Richard , Kate A. Graham , Alexis J. Matthew , Mathieu P.A. Hébert , Jérémie A. Doiron , Mathieu Johnson , Eric P. Allain , David A. Barnett , Sandra Turcotte , Luc H. Boudreau","doi":"10.1016/j.thromres.2025.109445","DOIUrl":"10.1016/j.thromres.2025.109445","url":null,"abstract":"<div><div>Megakaryocytes, a type of myeloid cell primarily produced in the bone marrow, are essential for releasing platelets into the bloodstream. Through platelet production, megakaryocytes transfer their own biological content to these cells, including inflammatory enzymes. Amongst these enzymes, 12-lipoxygenase (12-LO) has been shown to modulate platelet activation and is involved in several chronic inflammatory conditions. However, the role of 12-LO in megakaryocyte maturation and the subsequent release of platelets remains uninvestigated. This study demonstrates the importance of 12-LO expression in megakaryocyte maturation and functions. Flow cytometry and fluorescence microscopy were utilized to analyze DAMI cell differentiation. Inflammatory enzyme profiles were assessed through Western blot analysis and LC-MS/MS. To evaluate megakaryocyte functionality, platelet-type 12-LO knockout mice were employed. Differentiation of DAMI cells into mature megakaryocytes resulted in increased surface marker expression, enhanced platelet-like particle production, reduced cell proliferation, and elevated cell death. The arachidonic acid release from cell membranes was increased in differentiated cells as well as the expression of several inflammatory enzymes such as 12-LO, cyclooxygenase-1 and thromboxane synthase. The production of 12(<em>S</em>)-hydroxyeicosatetraenoic acid and thromboxane was also increased in these cells. In DAMI cells deficient in 12-LO expression (ALOX12<sup>−/−</sup>), we found no difference in CD41 expression following differentiation compared to ALOX12<sup>+/+</sup> cells. However, 12-LO-deficient cells produced fewer proplatelets and, consequently, fewer platelet-like particles. <em>In vivo</em>, platelet counts in 12-LO-deficient mice were comparable to those in wild-type mice, and the number of bone marrow megakaryocytes remained consistent between the groups. <em>Ex vivo</em> analysis revealed that megakaryocytes lacking 12-LO produced fewer platelets. These findings indicate that 12-LO may play a regulatory role in megakaryocyte function, particularly in proplatelet formation and platelet release.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109445"},"PeriodicalIF":3.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911789","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}
Nancy Charó , Roberto G. Pozner , Mara C.A.M. Aguiar , Silvio Tatti , Mirta Schattner , Ricardo M. Gómez
{"title":"Yellow fever virus infection triggers proinflammatory and prothrombotic responses in endothelial cells through NF-κB and MAPK signaling pathways","authors":"Nancy Charó , Roberto G. Pozner , Mara C.A.M. Aguiar , Silvio Tatti , Mirta Schattner , Ricardo M. Gómez","doi":"10.1016/j.thromres.2025.109439","DOIUrl":"10.1016/j.thromres.2025.109439","url":null,"abstract":"<div><div>Yellow fever (YF), caused by the Yellow Fever Virus (YFV), is a disease endemic in South America and Africa with clinical manifestations ranging from fever to fatal organ failure and hemorrhagic complications. The role of the endothelium in the pathogenesis of YFV is not completely understood. To investigate the effects of YFV infection on human endothelial cells (EC), human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1) were infected with the YFV 17DD strain. Viral infection, cell death, cell adhesion, adhesion molecules, cytokines, von Willebrand factor (VWF), nitric oxide (NO), tissue factor (TF), interferon-I, clotting time and signaling pathways were analyzed by plaque assays, immunofluorescence, cytometry, ELISA, RT-qPCR, DAF-FM DA probe, Griess reaction and Western blot.</div><div>The results showed that HUVEC and HMEC-1 were susceptible to YFV infection according to virus titer and presence of intracellular dsRNA, which induced an increase in apoptosis at 3- and 7-days post-infection (pi), respectively. At earlier time points (4–48 h pi), infected EC exhibited upregulation of E-selectin and ICAM-1, secretion of IL-1β, IL-6 and VWF, decreased eNOS mRNA, NO production, clotting time, and increased TF and interferon-I mRNA levels, as well as increased adhesion of platelets and leukocytes to EC. Mechanistically, YFV infection led to activation of the NF-κB and MAPK signaling pathways.</div><div>We conclude that YFV infection triggers a proinflammatory and prothrombotic response in EC that likely contributes to the vascular dysfunction and hemorrhagic manifestations observed in YF. These findings point to potential targets for therapeutic intervention.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109439"},"PeriodicalIF":3.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892818","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":"When clots go to court: Clinical insights from litigation for venous thromboembolism in orthopedic surgery","authors":"Kushal T. Kadakia , Behnood Bikdeli","doi":"10.1016/j.thromres.2025.109442","DOIUrl":"10.1016/j.thromres.2025.109442","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109442"},"PeriodicalIF":3.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902749","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}
Haad A. Arif , Andrew Miner , Simon T. Moore , Gavin LeBrun , Abbad Sultan , Joseph G. Elsissy
{"title":"Characteristics and outcomes of venous thromboembolism-related litigation in orthopaedic surgery","authors":"Haad A. Arif , Andrew Miner , Simon T. Moore , Gavin LeBrun , Abbad Sultan , Joseph G. Elsissy","doi":"10.1016/j.thromres.2025.109443","DOIUrl":"10.1016/j.thromres.2025.109443","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE) is a considerable source of morbidity, mortality, and economic burden within orthopaedic surgery. Our study aimed to analyze the characteristics and reasons for lawsuits pertaining to VTE levied against orthopaedic surgeons.</div></div><div><h3>Methods</h3><div>The Westlaw database was queried for cases filed between 1980 and 2023 against orthopaedic surgeons involving VTE, using the search terms “orthopaedic”, “blood clot,” “deep vein thrombosis,” “venous thromboembolism,” and “pulmonary embolism.”</div></div><div><h3>Results</h3><div>A total of 122 out of 371 cases were selected for inclusion in this study. A defendant verdict was reached in 84 (69 %) cases and a plaintiff-verdict in 23 (19 %) cases. Fifteen (12 %) cases were settled. The mean indemnity payment and settlement award were $2.39 million and $662 thousand, respectively. Discontinuation or failure to initiate post-discharge anticoagulation therapy was cited in 25 % of cases. The most common basis of litigation was diagnostic/therapeutic delay (42 %) and inadequate VTE prophylaxis (39 %). Death was the most frequently reported complication (64 %). Patient-reported pain and suffering was associated with a defendant verdict (p = 0.0204). The choice of anticoagulant was not found to increase the risk of a plaintiff-favorable verdict (p = 0.6754).</div></div><div><h3>Conclusions</h3><div>Malpractice cases related to VTE in orthopaedic surgery are associated with substantial financial liability and arise in the setting of delayed diagnosis of VTE or failure to initiate thromboprophylaxis. Current medicolegal trends do not indicate a preference for any specific VTE prophylactic agent. Implementing a systems-based strategy to optimize transitions of care may help reduce both the incidence of VTE and the associated risk of litigation.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109443"},"PeriodicalIF":3.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922543","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}
Stefanie Hammer , Leah Heuer , Günalp Uzun , Tamam Bakchoul , Karina Althaus
{"title":"Thromboelastographic assessment of hypofibrinolysis in stored plasma samples: A novel spike-in method","authors":"Stefanie Hammer , Leah Heuer , Günalp Uzun , Tamam Bakchoul , Karina Althaus","doi":"10.1016/j.thromres.2025.109430","DOIUrl":"10.1016/j.thromres.2025.109430","url":null,"abstract":"<div><h3>Introduction</h3><div>Congenital or acquired dysregulation of fibrinolytic system can lead to bleeding (hyperfibrinolysis) or thrombosis (hypofibrinolysis), with increased risk for multi-organ failure. Standard clotting-based assays provide limited insight into fibrinolytic status. In contrast, thromboelastography (TEG), a whole blood assay, offers a comprehensive assessment of the coagulation and fibrinolytic systems. While freezing plasma samples enables later investigation of plasmatic coagulation factors, viscoelastic testing (VT) requires immediate testing. In this study, we evaluated a new diagnostic approach to assess fibrinolysis in frozen plasma samples spiked into healthy whole blood using VT.</div></div><div><h3>Methods</h3><div>Citrated whole blood and corresponding frozen platelet-poor plasma (PPP) samples from patients with hypofibrinolytic disorders were analyzed using thromboelastography (TEG). The spike-in method involved reconstituting patient-derived frozen PPP into plasma-depleted blood from healthy subjects. In addition, the Lysis Timer®, a global fibrinolysis capacity assay, was used to assess fibrinolysis in plasma samples.</div></div><div><h3>Results</h3><div>The validation study showed strong correlation between lysis time (LT) of VT in healthy whole blood and spiked samples (r = 0.6720, p = 0.0012). Hypofibrinolytic patients exhibited significantly increased LT in the tissue plasminogen activator-test of VT (LT-TPA) when their PPP was spiked into healthy whole blood, confirming hypofibrinolytic activity (LT-TPA whole blood of healthy donors vs. spike-in with patients, PPP: 165.7 ± 16.6 s vs. 218.3 ± 39.6 s, p < 0.0001). The Lysis Timer assay supported these findings, suggesting a plasmatic factor rather than cell-derived resistance to fibrinolysis.</div></div><div><h3>Conclusion</h3><div>The spike-in approach can be used to retrospectively detect hypofibrinolysis in frozen samples using TEG. This method is particularly useful for clinical studies when immediate VT is not available.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"254 ","pages":"Article 109430"},"PeriodicalIF":3.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917558","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}