Research and Practice in Thrombosis and Haemostasis最新文献

{"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":"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":"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":"Extravascular factor IX after gene therapy in hemophilia B, does it matter?","authors":"Quentin Van Thillo ,&nbsp;Cédric Hermans","doi":"10.1016/j.rpth.2025.102723","DOIUrl":"10.1016/j.rpth.2025.102723","url":null,"abstract":"<div><div>Gene therapy will very likely change the treatment paradigm of hemophilia B in the coming years. For the majority of patients, adjunctive exogenous factor (F)IX clotting factor concentrate will continue to be needed in case of surgery or bleeding. However, there is insufficient evidence on the optimal FIX product to be used in these circumstances, given the differences in body distribution between the currently available products. Unknown factors include the behavior of FIX Padua in the extravascular space and its contribution to hemostasis. Other issues are the potential importance of the presence of cross-reactive material and the discrepancies between different assays in measuring FIX activity. In conclusion, even after gene therapy, the differences between different FIX products remain relevant for optimal bleeding and perioperative management. Thus, real-world data on the use of exogenous FIX after gene therapy are needed to determine the preferred exogenous FIX concentrate.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102723"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759588","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":"Protofibril packing density of individual fibers alters fibrinolysis","authors":"Rebecca A. Risman ,&nbsp;Victoria Percoco ,&nbsp;Bradley Paynter ,&nbsp;Brittany E. Bannish ,&nbsp;Valerie Tutwiler","doi":"10.1016/j.rpth.2025.102708","DOIUrl":"10.1016/j.rpth.2025.102708","url":null,"abstract":"<div><h3>Background</h3><div>Many diseased conditions alter the fibrinogen and clotting activator concentrations, resulting in a unique network structure that may be resistant or susceptible to lysis. While much is known about the relationship between structure and lysis, previous studies overlooked confounding factors in the fibrin network structure that must be considered to develop targeted therapeutics.</div></div><div><h3>Objectives</h3><div>We aimed to determine how fiber diameter, network pore size, and protofibril packing density work together and individually to impact lysis.</div></div><div><h3>Methods</h3><div>We used turbidimetry to kinetically monitor clot formation, protofibril packing, and lysis of clots formed with the 2 activators. We characterized the unique clot structures during lysis using confocal and scanning electron microscopy. With our stochastic multiscale mathematical model of fibrinolysis, we varied the fibrin content per fiber to probe the role of protofibril packing density on a clot’s susceptibility to degradation.</div></div><div><h3>Results</h3><div>Plasma clots activated with tissue factor had denser fibrin networks with looser protofibril packing that were initially degraded faster than clots activated with thrombin, which had loose fibrin networks and dense protofibril packing. Modeling revealed that the fibrin content per fiber dictates individual fiber lysis time and the time it takes tissue-type plasminogen activator to travel between fibers.</div></div><div><h3>Conclusion</h3><div>The present work highlights the crucial role that protofibril packing density plays in fibrinolysis. Our results suggest a need to consider the effect a disease has on protofibril packing density to inform about clot resistance and the development for more personalized lytic agents.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102708"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683444","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":"Efficacy and safety of plasma-derived von Willebrand factor/factor VIII concentrate (wilate) prophylaxis in children and adolescents with von Willebrand disease – WIL-31 study post hoc analysis","authors":"Robert F. Sidonio Jr. ,&nbsp;Leonid Dubey ,&nbsp;Kateryna V. Vilchevska ,&nbsp;Adlette Inati ,&nbsp;Claudia Djambas Khayat","doi":"10.1016/j.rpth.2025.102719","DOIUrl":"10.1016/j.rpth.2025.102719","url":null,"abstract":"<div><h3>Background</h3><div>Prophylaxis with von Willebrand factor is recommended in people with severe von Willebrand disease (VWD), regardless of age. WIL-31, the only prospective study with an on-demand run-in study as an intraindividual comparator, demonstrated the efficacy and safety of prophylaxis with the plasma-derived von Willebrand factor/factor VIII concentrate wilate (Octapharma) in adults and children with VWD of all types. Prophylaxis is often considered in young children and adolescents with severe VWD and recurrent bleeding, although limited data support this strategy.</div></div><div><h3>Objectives</h3><div>To assess the efficacy of wilate prophylaxis in children (6-11 years) and adolescents (12-16 years) in WIL-31.</div></div><div><h3>Methods</h3><div>Patients received 20 to 40 IU/kg (Octapharma) wilate prophylaxis 2 to 3 times weekly for 12 months. Results were compared with prospective on-demand treatment.</div></div><div><h3>Results</h3><div>Mean total annualized bleeding rates (ABRs) during on-demand vs prophylaxis were 32.5 vs 3.7 in children (<em>n</em> = 9) and 28.9 vs 4.3 in adolescents (<em>n</em> = 6), representing reductions of 89% and 85%, respectively. All 34 bleeds in children, and 20/26 (77%) bleeds in adolescents were minor. Mean spontaneous ABRs during prophylaxis were 2.5 in children and 1.5 in adolescents. The most common bleeding site in both groups and across all VWD types was the nose. ABRs were reduced further during the second 6 months of prophylaxis vs the first 6 months. During the second 6 months, 78% of children and 67% of adolescents had zero spontaneous bleeds. No serious adverse events related to study treatment or thrombotic events were observed.</div></div><div><h3>Conclusion</h3><div>wilate prophylaxis was efficacious and well-tolerated in children and adolescents with all types of VWD.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102719"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705640","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":"Fibrinogen levels and bleeding risk in adult extracorporeal cardiopulmonary resuscitation: multicenter observational study subanalysis","authors":"Seiya Kanou ,&nbsp;Eiji Nakatani ,&nbsp;Tetsumei Urano ,&nbsp;Hatoko Sasaki ,&nbsp;Akihiko Inoue ,&nbsp;Toru Hifumi ,&nbsp;Tetsuya Sakamoto ,&nbsp;Yasuhiro Kuroda ,&nbsp;Yoshihiro Tanaka","doi":"10.1016/j.rpth.2025.102700","DOIUrl":"10.1016/j.rpth.2025.102700","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102700"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563802","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":"Hemophilia treatments and the paradox of choice","authors":"Mike Makris ,&nbsp;Brian O’Mahony","doi":"10.1016/j.rpth.2025.102726","DOIUrl":"10.1016/j.rpth.2025.102726","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102726"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705638","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":"Addressing the perimenopause: what’s blood got to do with it?","authors":"Briony A. Cutts ,&nbsp;Kristy Fennessy","doi":"10.1016/j.rpth.2025.102698","DOIUrl":"10.1016/j.rpth.2025.102698","url":null,"abstract":"<div><div>A state of the art lecture titled, “Addressing the Perimenopause: What’s Blood Got to Do with It?” was presented at the International Society on Haemostasis and Thrombosis (ISTH) Congress in 2024. Perimenopause is when fluctuations of previously cyclically regulated hormones occur prior to menopause, resulting in a number of symptoms that can negatively impact a woman’s quality of life. Thrombosis and hemostasis experts are often approached to help investigate and manage clinical issues associated with perimenopause. This includes the safety of using menopause hormonal therapy in a past history or family history of venous thromboembolism, arterial thrombosis or thrombophilia, heavy menstrual bleeding, and iron deficiency anemia. A review of recent literature and clinical practice guidelines was undertaken to help determine the role of iron deficiency anemia in perimenopause, thrombotic risk in the setting of using menopause hormonal therapy, and indications for thrombophilia testing prior to commencing menopause hormonal therapy. Finally, we summarize relevant new data on this topic presented during the ISTH 2024 Congress.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102698"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580128","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":"Major bleeding and thromboembolism risks of antithrombotic treatment in patients with incident atrial fibrillation/flutter and a history of cancer","authors":"Nienke van Rein ,&nbsp;Gordon Chu ,&nbsp;Menno V. Huisman ,&nbsp;Lars Pedersen ,&nbsp;Henrik T. Sørensen ,&nbsp;Frederikus A. Klok ,&nbsp;Suzanne C. Cannegieter","doi":"10.1016/j.rpth.2025.102679","DOIUrl":"10.1016/j.rpth.2025.102679","url":null,"abstract":"<div><h3>Background</h3><div>Literature shows that atrial fibrillation (AF) patients with a history of cancer have a higher risk of thromboembolism (TE) and major bleeding (MB) compared to patients without. However, cancer type and time between cancer and AF diagnosis is often lacking in such analyses.</div></div><div><h3>Objectives</h3><div>To examine MB and TE rates of AF patients with a prior cancer diagnosis, stratified by cancer type and interval between cancer and AF diagnosis.</div></div><div><h3>Methods</h3><div>This Danish population-based cohort study included all patients aged ≥50 years with incident AF between January 1, 1995, and December 31, 2016, and identified those who had cancer before the AF diagnosis. From hospital and drug prescription databases, data on cancer type, time interval between cancer and AF diagnosis (ie, &lt;1, 1-3, or &gt;3 years), outcomes, and antithrombotic exposure were collected. Follow-up started from the AF diagnosis until the occurrence of an outcome or the end of the 2-year follow-up. Incidence rates (IRs) per 100 patient-years and adjusted hazard ratios (aHRs) with corresponding 95% CIs were calculated using Cox regression.</div></div><div><h3>Results</h3><div>We identified 39,178 patients with incident AF and a prior cancer diagnosis. These patients demonstrated higher MB (IR, 3.35 [3.25-3.45] vs 2.23 [2.29-2.35]) and TE rates (IR, 3.21 [3.11-3.31] vs 2.53 [2.50-2.56]) than those without prior cancer. The higher MB risk in AF patients with a prior cancer diagnosis was observed in all examined time intervals, while a higher TE risk was only observed in those with a cancer diagnosis &lt;1 year prior (aHR, 1.27 [1.16-1.40]). Prior respiratory cancer was associated with increased MB (aHR, 1.37 [1.26-1.48]) and TE risks (aHR, 1.26 [1.15-1.38]).</div></div><div><h3>Conclusion</h3><div>A prior cancer diagnosis confers additional MB and, to a lesser extent and in certain conditions, thromboembolic risks in patients with AF. The type and timing of the prior cancer diagnosis determines the degree of risk.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102679"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610930","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}