Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Stepwise response-guided treatment protocol superior to thrombopoietin receptor agonist-based second-line therapy for severe persistent/chronic immune thrombocytopenia: a multicenter prospective study from China","authors":"Lingling Fu ,&nbsp;Xi Lin ,&nbsp;Zhenping Chen ,&nbsp;Zhifa Wang ,&nbsp;Yan Liu ,&nbsp;Lijuan Wang ,&nbsp;Yu Hu ,&nbsp;Jingyao Ma ,&nbsp;Nan Wang ,&nbsp;Xiaoling Cheng ,&nbsp;Jie Ma ,&nbsp;Runhui Wu","doi":"10.1016/j.rpth.2025.102702","DOIUrl":"10.1016/j.rpth.2025.102702","url":null,"abstract":"<div><h3>Background</h3><div>The first second-line international recommendation for children with severe persistent/chronic immune thrombocytopenia is thrombopoietin receptor agonist (TPO-RA)-based treatment; however, &lt;30% can achieve sustained response off-treatment (SRoT), leading to a heavy medical burden.</div></div><div><h3>Objectives</h3><div>This study aimed to confirm the efficacy of the stepwise response-guided treatment protocol compared with TPO-RA–based second-line therapy for children with severe P/CITP.</div></div><div><h3>Methods</h3><div>The stepwise response-guided treatment protocol is an individualized stratified immune thrombocytopenia treatment starting with high-dose dexamethasone, then adding rituximab and TPO-RAs in sequential order according to treatment response. A prospective, multicenter clinical cohort study enrolled severe P/CITP children with a 1-year follow-up. We compared the treatment outcome response of platelet count, bleeding control, and treatment-related side effects and cost outcomes (escalation status, SRoT, and treatment costs) between the stepwise group and the TPO-RA–based second-line treatment group (TPO-RA group).</div></div><div><h3>Results</h3><div>The study enrolled 143 cases of severe P/CITP children with a 12-month follow-up period. There were no differences in baseline characteristics between the stepwise and TPO-RA groups (<em>P</em> &gt; .05). Response/remission rates and bleeding grades showed no differences (<em>P</em> &gt; .05), but there were fewer side effects related to treatment in the stepwise group (9.0%; <em>P</em> &lt; .00). A total of 74% in the stepwise group achieved SRoT while none in the TPO-RA group did. The cost of treatment was significantly lower in the stepwise group compared with the TPO-RA group over the 12-month follow-up period (USD 68.26/kg vs USD 384.76/kg, <em>P</em> &lt; .00).</div></div><div><h3>Conclusion</h3><div>The stepwise response-guided treatment protocol effectively stratifies children with severe P/CITP based on treatment response, enabling individualized treatment strategies. This protocol achieves comparable efficacy and safety while reducing the treatment burden compared with TPO-RA–based second-line therapy, making it a preferable option for children with severe P/CITP.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102702"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elderly patients are hyperresponsive to potent P2Y12 inhibitors","authors":"David Mutschlechner ,&nbsp;Maximilian Tscharre ,&nbsp;Patricia Pia Wadowski ,&nbsp;Silvia Lee ,&nbsp;Joseph Pultar ,&nbsp;Constantin Weikert ,&nbsp;Simon Panzer ,&nbsp;Thomas Gremmel","doi":"10.1016/j.rpth.2025.102704","DOIUrl":"10.1016/j.rpth.2025.102704","url":null,"abstract":"<div><h3>Background</h3><div>Aging has recently been associated with increased basal platelet activation and platelet hyperreactivity in response to adenosine diphosphate (ADP) but with decreased platelet response to thrombin receptor stimulation in individuals without antiplatelet therapy.</div></div><div><h3>Objectives</h3><div>To investigate platelet response to agonist stimulation in elderly patients (≥70 years) on dual antiplatelet therapy with potent P2Y12 inhibitors.</div></div><div><h3>Methods</h3><div>Platelet aggregation in response to arachidonic acid (AA), ADP, collagen, the protease-activated receptor-1 agonist SFLLRN, and the protease-activated receptor-4 agonist AYPGKF was assessed by multiple electrode aggregometry in 79 prasugrel- and 77 ticagrelor-treated patients 3 days after acute percutaneous coronary intervention.</div></div><div><h3>Results</h3><div>In the overall study population (<em>N</em> = 156), patients aged ≥70 years (<em>n</em> = 33) had lower platelet aggregation in response to AA, ADP, and SFLLRN than younger patients (all <em>P</em> &lt; .05). In prasugrel-treated patients (<em>n</em> = 79), those aged ≥70 years (<em>n</em> = 13) showed lower platelet aggregation in response to all agonists than younger patients (all <em>P</em> &lt; .05). In contrast, in ticagrelor-treated patients (<em>n</em> = 77), those aged ≥70 years (<em>n</em> = 20) only had lower ADP-inducible platelet aggregation than younger patients (<em>P</em> = .03), whereas platelet aggregation in response to AA, collagen, SFLLRN, and AYPGKF was similar between elderly and younger patients (all <em>P</em> &gt; .05). Among patients aged ≥70 years, prasugrel-treated patients showed lower platelet aggregation in response to AA, collagen, and AYPGKF than those receiving ticagrelor (all <em>P</em> &lt; .05).</div></div><div><h3>Conclusion</h3><div>Patients aged ≥70 years on potent P2Y12 inhibitors exhibit increased inhibition of ADP-inducible platelet aggregation. In addition, elderly patients on prasugrel show a lower response to AA, collagen, SFLLRN and AYPGKF than younger patients.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102704"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factor XI localization in human deep venous thrombus and function of activated factor XI on venous thrombus formation and hemostasis","authors":"Nobuyuki Oguri ,&nbsp;Toshihiro Gi ,&nbsp;Eriko Nakamura ,&nbsp;Kazunari Maekawa ,&nbsp;Eiji Furukoji ,&nbsp;Hoshimi Okawa ,&nbsp;Sho Kouyama ,&nbsp;Saki Horiuchi ,&nbsp;Akira Sawaguchi ,&nbsp;Tatefumi Sakae ,&nbsp;Minako Azuma ,&nbsp;Yujiro Asada ,&nbsp;Atsushi Yamashita","doi":"10.1016/j.rpth.2025.102720","DOIUrl":"10.1016/j.rpth.2025.102720","url":null,"abstract":"<div><h3>Background</h3><div>Novel anticoagulants targeting coagulation factor (F)XI/activated FXI (FXIa) are currently under development. However, whether FXI is present in human deep vein thrombosis (DVT) and whether FXIa and activated FX (FXa) play different roles in venous thrombus formation and hemostasis remain unclear.</div></div><div><h3>Objectives</h3><div>To determine the presence of FXI in DVT and the effects of direct oral FXIa and FXa inhibitors on venous thrombus formation and hemostasis in rabbits and on <em>in vitro</em> thrombus formation.</div></div><div><h3>Methods</h3><div>We immunohistochemically assessed FXI localization in human-aspirated DVT (<em>n</em> = 15). Additionally, we compared thrombus formation induced by endothelial denudation and stenosis or stasis in the jugular vein and skin bleeding time and volume between rabbits treated with direct FXIa inhibitors (ONO-1600586) and FXa inhibitors (rivaroxaban). <em>Ex vivo</em> rabbit and human blood were perfused in a flow chamber under low-shear rates (70/s).</div></div><div><h3>Results</h3><div>FXI was localized in all DVT, predominantly in fibrin-rich areas. The FXI immunopositive area in the nonorganizing area was greater than that in the organizing area. Although FXIa and FXa inhibitors comparably inhibited venous thrombus formation, FXIa inhibitors did not affect bleeding time or volume in rabbits. FXIa or FXa inhibitors mildly or strongly inhibited fibrin formation at low-shear rates, respectively. Furthermore, the FXIa inhibitor suppressed human FXIa activity, thrombin generation, and fibrin formation during perfusion.</div></div><div><h3>Conclusion</h3><div>The pathologic findings of human DVT suggest FXI’s role in human DVT. FXIa inhibitors may inhibit less fibrin formation than FXa inhibitors and may explain the minor role of FXIa in hemostasis.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102720"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes of cancer-associated isolated distal deep vein thrombosis: a comparison between asymptomatic and symptomatic thrombosis—findings from the ONCO DVT Study","authors":"Yoshito Ogihara ,&nbsp;Yugo Yamashita ,&nbsp;Takeshi Morimoto ,&nbsp;Nao Muraoka ,&nbsp;Michihisa Umetsu ,&nbsp;Yuji Nishimoto ,&nbsp;Takuma Takada ,&nbsp;Tatsuya Nishikawa ,&nbsp;Nobutaka Ikeda ,&nbsp;Kazunori Otsui ,&nbsp;Daisuke Sueta ,&nbsp;Yukari Tsubata ,&nbsp;Masaaki Shoji ,&nbsp;Ayumi Shikama ,&nbsp;Yutaka Hosoi ,&nbsp;Yasuhiro Tanabe ,&nbsp;Ryuki Chatani ,&nbsp;Kengo Tsukahara ,&nbsp;Naohiko Nakanishi ,&nbsp;Kitae Kim ,&nbsp;Kaoru Dohi","doi":"10.1016/j.rpth.2025.102722","DOIUrl":"10.1016/j.rpth.2025.102722","url":null,"abstract":"<div><h3>Background</h3><div>The risk of recurrent venous thromboembolism (VTE) in patients with isolated distal deep vein thrombosis (IDDVT) is generally low, particularly when IDDVT is asymptomatic. However, cancer patients with IDDVT, even asymptomatic IDDVT, may be at a higher risk of recurrent VTE.</div></div><div><h3>Objectives</h3><div>To compare the clinical outcomes of cancer patients with asymptomatic and symptomatic IDDVT.</div></div><div><h3>Methods</h3><div>The ONCO DVT trial is a randomized clinical trial that compared 12-month versus 3-month edoxaban treatment regimens in cancer patients with IDDVT. In this post hoc analysis, 601 patients were categorized into the asymptomatic (<em>n</em> = 479) and symptomatic (<em>n</em> = 122) groups based on IDDVT-related symptoms at diagnosis. The primary outcome was the composite of symptomatic recurrent VTE or VTE-related death at 12 months, while the major secondary outcome was major bleeding at 12 months.</div></div><div><h3>Results</h3><div>The cumulative 12-month incidence of the primary outcome was lower in the asymptomatic group than that in the symptomatic group (2.9% vs 13.4%; <em>P</em> &lt; .001; hazard ratio, 0.21; 95% CI, 0.10-0.47). Among the 12 patients with symptomatic recurrent VTE in the asymptomatic group, 8 (67%) had recurrent IDDVT, and 11 (92%) experienced recurrence after discontinuing anticoagulation therapy. The cumulative 12-month incidence of major bleeding was lower in the asymptomatic group than that in the symptomatic group (7.8% and 13.2%; <em>P</em> = .048).</div></div><div><h3>Conclusion</h3><div>The risk of recurrent symptomatic VTE was lower in cancer patients with asymptomatic IDDVT than in those with symptomatic IDDVT. Most recurrent VTE events were recurrent IDDVT, with the majority occurring after discontinuing anticoagulation therapy.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102722"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid signatures of immunothrombosis: insights from VITT","authors":"Tamam Bakchoul,&nbsp;Madhumita Chatterjee","doi":"10.1016/j.rpth.2025.102725","DOIUrl":"10.1016/j.rpth.2025.102725","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102725"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Platelet factor 4 immunothrombosis—not just heparin and vaccine triggers","authors":"Luisa Müller ,&nbsp;Jing Jing Wang ,&nbsp;Venkata A.S. Dabbiru ,&nbsp;Thomas Thiele ,&nbsp;Linda Schönborn","doi":"10.1016/j.rpth.2025.102729","DOIUrl":"10.1016/j.rpth.2025.102729","url":null,"abstract":"<div><div>Derailments at the tightly regulated interface of blood coagulation and innate inflammatory immune responses can lead to pathologic immunothrombosis. A special subset of immunothrombosis is caused by antibodies against platelet-factor 4 (PF4). Anti-PF4 antibodies triggered by heparin treatment in heparin-induced thrombocytopenia (HIT) are known for more than 50 years. Interest in anti-PF4 disorders rekindled when first cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) occurred during the worldwide COVID-19 vaccination campaign. During this time new diagnostic procedures were established to identify affected patients and to differentiate between different kinds of anti-PF4 antibodies. This review article gives an overview about the current knowledge of HIT and VITT with concepts of the underlying pathogenesis. In addition to heparin and vaccination as known triggers for HIT and VITT, concepts for other clinical cases with anti-PF4 antibodies are described in more detail. Anti-PF4 antibodies in atypical HIT-like syndromes could be triggered by presentation of various polyanions, eg, in settings of orthopedic surgery or bacterial infections. Anti-PF4 antibodies in acute VITT-like disorders can occur after viral infections. Chronic VITT-like anti-PF4 antibodies causing recurrent thrombosis and thrombocytopenia are often linked to monoclonal gammopathies. For all disorders with anti-PF4 antibodies, timely identification in patients with thrombocytopenia with or without thrombosis is crucial for successful therapy.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102729"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unresolved issues in the diagnosis and management of thrombotic antiphospholipid syndrome","authors":"Deepa J. Arachchillage ,&nbsp;Mike Laffan","doi":"10.1016/j.rpth.2025.102724","DOIUrl":"10.1016/j.rpth.2025.102724","url":null,"abstract":"<div><div>Antiphospholipid syndrome (APS) is a highly prothrombotic autoimmune disease characterized by the persistent presence of antiphospholipid autoantibodies (aPL) in association with thrombotic or nonthrombotic macro- and microvascular manifestations and/or pregnancy complications. This review is restricted to thrombotic APS. Since the publication of the American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for APS, several authors have emphasized the difference between “classification” and “diagnosis” as a potential pitfall for clinicians. In addition to challenges associated with the diagnosis of APS, there are many unresolved areas in understanding pathogenesis and in the management of both thrombotic and obstetric APS. Although APS is an antibody-mediated autoimmune disease, secondary thrombosis prevention is achieved by anticoagulation, mainly with vitamin K antagonists, such as warfarin, rather than immunomodulation. Evidence is convincing for the use of vitamin K antagonists in triple-positive APS with venous thromboembolism. However, the best anticoagulant approach in the management of venous thromboembolism patients with single or dual positive aPL is not clear. Management of patients with stroke or arterial thrombosis with aPL remains a major unresolved issue, although some guidelines recommend the use of warfarin rather than antiplatelet therapy as the first-line treatment of stroke in APS. Recurrent thrombosis, despite therapeutic anticoagulation, remains a frequent problem and may be explained by the contribution of thrombo-inflammation in patients with thrombotic APS. In this narrative review, we discuss some of the unresolved issues in the diagnosis and management of thrombotic APS.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102724"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic factors for recurrence in acquired hemophilia A-results from a long-term observational study","authors":"Lisa Reich,&nbsp;Florian Gatzke,&nbsp;Steffen Rauchfuss,&nbsp;Stefanie Roth,&nbsp;Wolfgang Miesbach","doi":"10.1016/j.rpth.2025.102707","DOIUrl":"10.1016/j.rpth.2025.102707","url":null,"abstract":"<div><h3>Objectives</h3><div>Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against factor (F)VIII (FVIII), potentially leading to life-threatening bleeding. While predictors for remission have been analyzed, data on recurrence is lacking.</div></div><div><h3>Methods</h3><div>This study investigated predictors of AHA recurrence in 41 patients. Patients were divided into 2 groups: those with recurrence (<em>n</em> = 18) and those in stable long-term remission (<em>n</em> = 23) with at least 1 year of follow-up.</div></div><div><h3>Results</h3><div>All relapses occurred within 1 year of initial remission. The median follow-up period was 3.8 years (IQR, 1.8-6.4) for all included patients. Multivariate Cox regression analysis revealed that initial FVIII activity &lt;1 IU/dL and failure to achieve initial complete remission (CR) were significant predictors of relapse. Kaplan–Meier curves showed significantly different relapse-free survival rates for patients with initial FVIII activity &lt;1 IU/dL vs ≥1 IU/dL (χ²[1] = 5.950, <em>P</em> = .015), and for those achieving initial CR vs partial remission (χ²[1] = 6.570, <em>P</em> = .010).</div><div>Other factors such as inhibitor titer, gender, age, World Health Organization scale, underlying disorder, controlled disorder, initial immunosuppressive therapy, immunosuppressive therapy escalation, and partial remission at day 21 showed no significant relation to recurrences. Overall survival did not differ significantly between relapsing and nonrelapsing patients (χ²[1] = .896, <em>P</em> = .344).</div></div><div><h3>Conclusion</h3><div>Initial FVIII &lt;1 IU/dL and failure to achieve initial CR are identified as risk factors for recurrence in AHA. Patients with these characteristics should be closely monitored for at least 1 year after initial remission due to increased recurrence risk.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102707"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the plasma proteomic profile of patients at risk of thromboembolic events","authors":"Eva R. Smit ,&nbsp;Iris C. Kreft ,&nbsp;Eleonora Camilleri ,&nbsp;J. Louise I. Burggraaf-van Delft ,&nbsp;Nienke van Rein ,&nbsp;Bart J.M. van Vlijmen ,&nbsp;Anne-Marije Hulshof ,&nbsp;Bas C.T. van Bussel ,&nbsp;Frank van Rosmalen ,&nbsp;Carmen van der Zwaan ,&nbsp;Tom van de Berg ,&nbsp;Yvonne Henskens ,&nbsp;Hugo ten Cate ,&nbsp;Jonathan M. Coutinho ,&nbsp;Marieke J.H.A. Kruip ,&nbsp;Jeroen J.C. Eikenboom ,&nbsp;Arie J. Hoogendijk ,&nbsp;Suzanne C. Cannegieter ,&nbsp;Maartje van den Biggelaar ,&nbsp;Mihaela Zlei","doi":"10.1016/j.rpth.2025.102713","DOIUrl":"10.1016/j.rpth.2025.102713","url":null,"abstract":"<div><h3>Background</h3><div>The elevated health burden of thromboembolic events necessitates development of blood-based risk monitoring tools.</div></div><div><h3>Objectives</h3><div>We explored the potential of mass spectrometry–based plasma proteomics to provide insights into underlying plasma protein signatures associated with treatment and occurrence of thromboembolic events.</div></div><div><h3>Methods</h3><div>Utilizing a high-throughput, data-independent acquisition, discovery-based proteomics workflow, we analyzed 434 plasma proteomes from different groups of individuals with elevated risk of thromboembolic events, including individuals I) on vitamin K antagonists (VKAs; <em>n</em> = 130), II) with a prior venous thromboembolism (<em>n</em> = 10), III) with acute cerebral venous sinus thrombosis (<em>n</em> = 10, and IV) with SARS-CoV-2 infection (<em>n</em> = 67). Plasma protein levels measured with mass spectrometry were correlated with international normalized ratio and conventional clinical laboratory measurements. Plasma profile differences between different groups were assessed using principal component analysis, moderated <em>t</em>-test, and clustering analysis.</div></div><div><h3>Results</h3><div>Plasma protein levels were in agreement with conventional clinical laboratory parameters, including albumin and fibrinogen. Levels of vitamin K–dependent proteins inversely correlated with international normalized ratio. In the individual studies, we found decreased levels of vitamin K–dependent coagulation proteins in patients on VKAs, alterations in inflammatory signatures among CVST patients and a distinctive signature indicative of SARS-CoV-2 infection. However, no protein signature associated with a thromboembolic event could be identified neither in individual nor combined studies.</div></div><div><h3>Conclusion</h3><div>Although VKA treatment–specific and disease-specific signatures were captured, our study highlights that the challenges of discovering biomarkers in patients at risk of thromboembolic events lie in the heterogeneity of individual plasma profiles in relation to treatment and etiology.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102713"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise capacity, dyspnea, and quality of life 6 months after exercise-based rehabilitation in patients with persistent dyspnea following pulmonary embolism","authors":"Stacey Haukeland-Parker ,&nbsp;Øyvind Jervan ,&nbsp;Waleed Ghanima ,&nbsp;Martijn A. Spruit ,&nbsp;René Holst ,&nbsp;Jostein Gleditsch ,&nbsp;Mazdak Tavoly ,&nbsp;Knut Stavem ,&nbsp;Kjetil Steine ,&nbsp;Dan Atar ,&nbsp;Anders Erik Astrup Dahm ,&nbsp;Frederikus A. Klok ,&nbsp;Hege Hølmo Johannessen","doi":"10.1016/j.rpth.2025.102736","DOIUrl":"10.1016/j.rpth.2025.102736","url":null,"abstract":"<div><h3>Background</h3><div>Exercise is safe and effective in the short-term following pulmonary embolism. To date, little is known about the long-term effects.</div></div><div><h3>Objectives</h3><div>The aim of the study was to investigate whether the effects of exercise-based rehabilitation are maintained 6 months after completion in patients with persistent dyspnea following pulmonary embolism when compared with usual care.</div></div><div><h3>Methods</h3><div>A 2-center, randomized controlled trial compared 8 weeks of exercise-based rehabilitation with usual care. Patients were reassessed postintervention and 6 months later. Exercise capacity was measured with the incremental shuttle walk test (ISWT). Dyspnea was assessed with the Shortness of Breath Questionnaire, and health-related quality of life was assessed with disease-specific (Pulmonary Embolism Quality of Life Questionnaire) and generic questionnaires.</div></div><div><h3>Results</h3><div>In total, 159 of 211 randomized patients attended follow-up 6 months postintervention. The significant improvement on the ISWT in the rehabilitation group was maintained at the 6-month follow-up (96 m; SE: 15 m; 95% CI: 66, 127). There were no changes on the ISWT in the control group at either time point. From postintervention to 6×-month follow-up, the rehabilitation group had further improvements in dyspnea compared with the control group (−3 points; SE: 1.4; 95% CI: −6, −1; <em>P</em> = .02). Health-related quality of life improved in both groups although superior improvements were seen in the rehabilitation group.</div></div><div><h3>Conclusion</h3><div>The improvement in exercise capacity after 8 weeks of exercise-based rehabilitation in patients with pulmonary embolism and persistent dyspnea was maintained at the 6-month follow-up, while no improvement was observed in the control group, highlighting the relevance of offering rehabilitation to these patients.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102736"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}