Journal of Thrombosis and Haemostasis最新文献

{"title":"Clinical characteristics and prognosis of patients with central pulmonary embolism.","authors":"Robin V Hofstetter, Odile Stalder, Tobias Tritschler, Marie Méan, Nicolas Rodondi, Marc Righini, Drahomir Aujesky","doi":"10.1016/j.jtha.2025.02.007","DOIUrl":"10.1016/j.jtha.2025.02.007","url":null,"abstract":"<p><strong>Background: </strong>The impact of central localization of pulmonary embolism (PE) on clinical outcomes is uncertain.</p><p><strong>Objectives: </strong>To compare clinical presentation, risk factors, and outcomes between patients with central pulmonary embolism (cPE) and non-cPE.</p><p><strong>Methods: </strong>We retrospectively analyzed 597 patients with acute PE from the prospective SWITCO65+ cohort between September 2009 and December, 2013. cPE was defined as an embolus in the pulmonary trunk or the left or right pulmonary artery. We compared baseline clinical characteristics and outcomes at 3 months (recurrent venous thromboembolism [VTE], overall/PE-related mortality, PE-related quality of life) and over the entire follow-up (recurrent VTE, overall/PE-related mortality) between patients with cPE vs non-cPE. We examined the association between PE localization and recurrent VTE and overall mortality, adjusting for multiple confounders including thrombolysis, periods of anticoagulation, and competing risk of non-VTE-related death if appropriate.</p><p><strong>Results: </strong>Overall, 217 (36.3%) patients had cPE. Symptoms/signs of respiratory distress, right ventricular dysfunction, and myocardial injury were more prevalent in those with cPE. VTE recurrence, overall/PE-related mortality, and PE-related quality of life at 3 months did not vary by PE localization. After a median follow-up of 29.6 months, patients with cPE had a higher risk of fatal PE (5.5% vs 2.1%; P = .033). After adjustment, cPE was associated with recurrent VTE (subhazard ratio, 2.22; 95% CI, 1.25-3.91) but not with overall mortality (hazard ratio, 0.74; 95% CI, 0.45-1.21) during follow-up.</p><p><strong>Conclusion: </strong>cPE was associated with a 2.2-fold increased risk of recurrent VTE compared to non-cPE. Whether an extended anticoagulation duration could reduce the recurrence risk following cPE should be further examined.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arterial thromboembolic events in testicular cancer patients: short- and long-term incidence, risk factors, and impact on mortality.","authors":"Florian Moik, Angelika Terbuch, Ariane Sprakel, Georg Pichler, Dominik A Barth, Renate Pichler, Peter Rainer, Günther Silbernagel, Sebastian Mannweiler, Philipp J Jost, Sascha A Ahyai, Thomas Bauernhofer, Georg C Hutterer, Martin Pichler","doi":"10.1016/j.jtha.2025.01.022","DOIUrl":"10.1016/j.jtha.2025.01.022","url":null,"abstract":"<p><strong>Background: </strong>Patients with testicular germ cell tumors (TGCT) have a high cancer-specific survival rate.</p><p><strong>Objectives: </strong>We aimed to determine the short- and long-term risk of arterial thromboembolic events (ATE), their impact on mortality, and risk factors for ATE in TGCT patients.</p><p><strong>Methods: </strong>Patients with TGCT treated between 1994 and 2020 were included in a single-center retrospective cohort study. The primary outcome was ATE (ie, acute coronary syndrome, ischemic stroke, and acute peripheral arterial occlusion). Cumulative incidences were obtained in competing risk analysis. The impact of ATE on mortality was analyzed in a multistate model. Cox regression was used to explore short- and long-term ATE risk factors.</p><p><strong>Results: </strong>Overall, 1277 patients were included (median age, 35 years; seminoma: 56%; 44% cisplatin-based chemotherapy). Cumulative ATE incidences at 1, 10, and 25 years were 0.6% (95% CI, 0.3%-1.1%), 2.6% (95% CI, 1.8%-3.7%), and 12.0% (95% CI, 8.7%-15.9%), respectively. ATE diagnosis was independently associated with increased all-cause mortality (age-adjusted transition hazard ratio, 4.61; [95% CI, 2.40-8.85]; P < .001). Cisplatin-based chemotherapy was associated with ATE risk within 1 year after TGCT diagnosis (1.4% vs 0%, P < .001), whereas no differences were observed thereafter. Regarding long-term ATE risk, a point-based risk score was derived (age ≥ 35, smoking, and lactate dehydrogenase ≥ 250 IU/L), which efficiently stratified ATE risk (Harrel's C, 0.71 [95% CI, 0.63-0.78]), with cumulative ATE incidences in low-, intermediate-, and high-risk patients of 3.9%, 11.4%, and 22.7%, respectively.</p><p><strong>Conclusion: </strong>ATE represents a common complication in TGCT survivors and is associated with increased mortality. A simple point-based score efficiently stratifies long-term ATE risk, whereas cisplatin-based chemotherapy increases short-term ATE risk.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galloylated polyphenols represent a new class of antithrombotic agents with broad activity against thiol isomerases.","authors":"Moua Yang, Ivan Hancco Zirena, Quinn P Kennedy, Anika Patel, Glenn Merrill-Skoloff, Kelsey D Sack, Emmy Fulcidor, Christina Scartelli, Shihui Guo, Roelof H Bekendam, Osamede C Owegie, Huanzhang Xie, Ionita C Ghiran, Oren Levy, Lin Lin, Robert Flaumenhaft","doi":"10.1016/j.jtha.2025.01.021","DOIUrl":"10.1016/j.jtha.2025.01.021","url":null,"abstract":"<p><strong>Background: </strong>Both protein disulfide isomerase (PDI) and SARS-CoV-2 main protease (M^pro) are reliant on active-site cysteines stabilized by adjacent amino acids. We reasoned that redox-active compounds might interfere with both enzymes by acting in the vicinity of these reactive sites thus interfering with viral replication and thrombus formation. Our previous screen of 1019 flavonoids identified several compounds that inhibit SARS-CoV-2 M^pro.</p><p><strong>Objectives: </strong>Our goal was to identify phytochemical inhibitors of SARS-CoV-2 M^pro that block thiol isomerases and are antithrombotic.</p><p><strong>Methods: </strong>PDI, ERp57, ERp5, ERp46, isolated domains of PDI, and PDI mutants were used to evaluate the effects of galloylated polyphenols and their analogs on thiol isomerase reductase activity. Laser-injury and ferric chloride models of thrombus formation and a tail snip assay were used to assess the effects on thrombosis and hemostasis.</p><p><strong>Results: </strong>Pinocembrin 7-O-(3''-galloyl-4'',6''-(S)-hexahydroxydiphenoyl)-β-D-glucose (PGHG) inhibited both PDI and SARS-CoV-2 M^pro. Evaluation of isolated PDI fragments and active-site cysteine mutants showed that PGHG acts at the catalytic domains. Structure-function studies showed that PGHG interacts with histidines within the Cys53-Gly54-His55-Cys56 motifs of PDI. PGHG was equally active against other thiol isomerases, including ERp57, ERp5, ERp72, and ERp46. Screening numerous galloylated polyphenols demonstrated a class effect on thiol isomerase inhibition. Structure-activity relationships indicated that the galloyl moieties within large galloylated polyphenols were important for their inhibitory activity. PGHG and punicalagin were antithrombotic in murine models of thrombus formation.</p><p><strong>Conclusions: </strong>Galloylated polyphenols represent a large class of antithrombotic compounds with broad activity against thiol isomerases. Many of these compounds also inhibit SARS-CoV-2 M^pro and viral replication.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward standardization and a concerted vision for platelet proteomics research: communication from the SSC of the ISTH.","authors":"Patricia Martínez-Botía, Samuel Tassi Yunga, Paulina Szklanna, Ozgun Babur, Andrew Emili, Phillip A Wilmarth, Johan W M Heemskerk, Patricia B Maguire, Aaron F J Iding, Sofia Ramström, Ángel García, Joseph E Aslan, Laura Gutiérrez","doi":"10.1016/j.jtha.2025.02.002","DOIUrl":"10.1016/j.jtha.2025.02.002","url":null,"abstract":"<p><p>Over the past 3 decades, omics technologies have revolutionized our understanding of platelet molecular content and organization, enabling the systematic analyses of platelet physiology. Among these approaches, proteomics has been especially significant in discovering as well as validating molecular mechanisms of platelet function in health and disease. However, several conceptual and practical challenges continue to limit the full utility of platelet proteomics tools and data. Methodological and analytical inconsistencies remain a key concern, with biological and technical variables exerting substantial influence on study outcomes and interpretation. These issues are compounded by the rapid pace of proteomics tool development and dataset collection, outstripping efforts to standardize best practices and ensure consensus, as platelet proteomics consolidates itself as a tool for research even outside the thrombosis and hemostasis field. In this communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee, we highlight recent advances in platelet proteomics studies, and we identify where collective efforts can strengthen experimental design, execution, and analysis. As a practical recommendation, we encourage platelet biologists to recognize current discrepancies and advance efforts to standardize and customize methods and reporting practices, including blood collection, platelet isolation, data acquisition, and data interpretation. By aligning protocols and ensuring detailed reporting, the field can more effectively integrate proteomics findings and accelerate our understanding of platelet biology.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet lipidomics indicates enhanced thrombocyte activation in patients with antiphospholipid syndrome in vivo.","authors":"Susanne Heimerl, Marcus Höring, Ralph Burkhardt, Matthias Höpting, Alexander Sigruener, Gerhard Liebisch, Christina Hart","doi":"10.1016/j.jtha.2025.01.020","DOIUrl":"10.1016/j.jtha.2025.01.020","url":null,"abstract":"<p><strong>Background: </strong>Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies in patients with thromboembolic/thromboinflammatory events and/or obstetric complications.</p><p><strong>Objectives: </strong>The aim of this study was to examine whether there are alterations in the platelet lipidome of APS patients in comparison with patients affected by thromboembolism without APS (control) and healthy volunteers.</p><p><strong>Methods: </strong>We applied quantitative mass spectrometry-based lipidomics to investigate the platelet lipidome of isolated resting and thrombin-stimulated platelets as well as platelet release in patients with APS, controls, and healthy volunteers.</p><p><strong>Results: </strong>Lipidomic data revealed an increase in lysophospholipids (LPLs) in platelets from APS patients, specifically in lysophosphatidylcholine and lysophosphatidylethanolamine species. As LPLs are cleavage products generated by phospholipase A (PLA) from the corresponding phospholipid precursor, LPL/phospholipid ratios may be employed as surrogates for PLA1 and PLA2 activities. The surrogate ratios for PLA2, which participates in the release of arachidonic acid during platelet activation, were significantly increased in APS in both resting platelets and upon thrombin-induced activation for phosphatidylcholine and phosphatidylethanolamine. The phosphatidylcholine-PLA2 surrogate ratio was found to correlate with serum levels of anti-β2-glycoprotein I and anticardiolipin immunoglobulin G. Finally, receiver operator characteristic analysis demonstrated excellent discrimination of patients with APS from controls and healthy volunteers.</p><p><strong>Conclusion: </strong>These findings provide substantial evidence that platelet activation is enhanced in APS in vivo, involving the activation of PLA2.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delphi consensus recommendations for neuraxial anesthesia in adults with platelet disorders and coagulation defects: communication from the ISTH SSC Subcommittee on von Willebrand Factor.","authors":"Wynn Peterson, Rachel Martin, Donald Arnold, Brendan Carvalho, Adam Cuker, Jeff Gadsden, Drew Provan, Natalia Rydz, Eliane Shore, David Kuter, Peter Kouides, Michelle Lavin, Paula James, Dale Engen, Michelle Sholzberg","doi":"10.1016/j.jtha.2025.01.019","DOIUrl":"10.1016/j.jtha.2025.01.019","url":null,"abstract":"<p><p>Neuraxial anesthesia is used for pain management in surgical and nonsurgical settings. Spinal/epidural hematomas likely occur in between 1:10 000 and 1:200 000 procedures. Risk is believed to be greater in patients with bleeding disorders/thrombocytopenia, and there are no existing comprehensive recommendations to guide neuraxial anesthesia in these patients. The study's objective was to develop recommendations to advise clinicians on treatment thresholds for neuraxial anesthesia in patients with platelet disorders/coagulation defects. A 4-round electronic modified Delphi consensus study was conducted. A steering committee generated the original Delphi statements and refined them based on panelist feedback. Consensus was achieved if ≥70% of participants agreed/strongly agreed or disagreed/strongly disagreed with a statement. This project was endorsed by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Subcommittee on von Willebrand Factor. Forty-five experts participated (42% response rate) with an essentially equal number of hematologists and anesthesiologists. Thirty consensus statements were developed for 11 disorders ranging from various causes of thrombocytopenia, inherited platelet function disorders, and single or multiple coagulation defects in obstetrical and nonobstetrical patients. Risk of sampling bias is present due to a predominantly North American sample, attrition (common in Delphi studies), and steering committee participation in the Delphi rounds. This is the first set of consensus recommendations for neuraxial anesthesia in adult patients with an array of platelet disorders/coagulation defects. These recommendations, based on the best available evidence and expert opinion, provide a decision framework for clinicians when faced with this challenging scenario.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring and reporting the composition of plasma and serum to improve biobanks and comparability of extracellular vesicle research: communication from the ISTH SSC Subcommittee on Vascular Biology.","authors":"Rienk Nieuwland, Fabrice Lucien, Dakota Gustafson, Metka Lenassi, Kimberly Martinod, Yohei Hisada","doi":"10.1016/j.jtha.2025.01.012","DOIUrl":"10.1016/j.jtha.2025.01.012","url":null,"abstract":"<p><p>Transparent reporting is key to improving the reproducibility of scientific research. In 2023, the International Society for Extracellular Vesicles updated the \"Minimal information for studies of extracellular vesicles\" (MISEV) reporting guidelines and published new recommendations for blood extracellular vesicle (EV) research entitled \"MIBlood-EV: Minimal information to enhance the quality and reproducibility of blood extracellular vesicle research.\" The MIBlood-EV recommendations are part of MISEV 2023 and promote reporting not only the protocols used for blood collection and handling but also the composition of the prepared samples that are used to measure EVs. Plasma and serum are commonly used starting materials for EV research; reporting their composition can help to improve reproducibility, comparison of measurement results, and support evidence-based guideline development. We conducted an online survey among the International Society on Thrombosis and Haemostasis (ISTH) EV researchers. Of the 20 respondents, 95% were familiar with MISEV, but 35% were unaware of the 2023 update, and only 65% applied these guidelines to their reports. With regard to MIBlood-EV, 40% were unaware of this reporting tool, and 20% did not follow its recommendations. This is surprising because most respondents agree that preanalytical variables of blood EV research are not satisfactorily described (75%), confirm that having a standardized reporting tool is beneficial for blood EV research (90%), and consider MIBlood-EV applicable to other fields of ISTH research (80%). In this Scientific and Standardization Committee communication, we summarize the survey results, as well as the background and goals of MISEV and how MIBlood-EV can be useful to improve the reproducibility of blood research within the ISTH community.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rapid whole-blood adenosine triphosphate secretion test can be used to exclude platelet-dense granule deficiency.","authors":"Minka Zivkovic, Roger E G Schutgens, Vossa van der Vegte, Janoek A Lukasse, Mark Roest, Dana Huskens, Annick S de Moor, Idske C L Kremer Hovinga, Rolf T Urbanus","doi":"10.1016/j.jtha.2025.01.013","DOIUrl":"10.1016/j.jtha.2025.01.013","url":null,"abstract":"<p><strong>Background: </strong>Delta storage pool disease (δ-SPD) is a rare platelet function disorder (PFD) characterized by a deficiency of dense granules or defective granule secretion, leading to bleeding diathesis. Diagnostics of δ-SPD are difficult and lack standardization, leading to underestimation of its prevalence. Current diagnostic methods are based on granule content assays or lumi-aggregometry, which have limited availability. Therefore, there is an unmet need for a rapid, accessible test for δ-SPD.</p><p><strong>Objectives: </strong>To evaluate the diagnostic value of a rapid whole-blood adenosine triphosphate (ATP) secretion test for δ-SPD.</p><p><strong>Methods: </strong>ATP secretion after PAR-1 activating peptide (PAR-1 AP; TRAP-6) stimulation was assessed in whole blood using luminescence in 50 healthy controls, 22 patients with a suspected PFD other than storage pool disease (non-SPD) and 25 patients with δ-SPD and corrected for platelet count. Diagnostic value of the test was determined with C-statistics, sensitivity, specificity, likelihood ratios (LLRs), and predictive values (PVs).</p><p><strong>Results: </strong>PAR-1 AP mediated ATP secretion in the rapid test was lower in δ-SPD than in healthy controls and non-SPD patients (P < .0001). The rapid test was able to discriminate between δ-SPD and non-SPD patients (C-statistic 0.88; 95% CI, 0.78-0.98). At a cutoff value of the highest value of the δ-SPD group, the sensitivity was 100% and the specificity was 64%. This cutoff value corresponded with a positive LLR of 2.75, an optimal negative LLR of 0.00, positive PV of 76%, and negative PV of 100%.</p><p><strong>Conclusion: </strong>A whole-blood ATP secretion test can be used to exclude ẟ-SPD in patients presenting with a primary hemostasis defect.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basics of diagnosis and treatment of venous thromboembolism.","authors":"Catrin Cox, Lara N Roberts","doi":"10.1016/j.jtha.2025.01.009","DOIUrl":"10.1016/j.jtha.2025.01.009","url":null,"abstract":"<p><p>Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism (PE), is common and associated with significant morbidity and mortality. The symptoms and signs of VTE are nonspecific. Well-established integrated diagnostic strategies combining clinical probability scores and D-dimer are used to identify patients with a low probability of VTE, where the diagnosis can be safely excluded without imaging. In patients with confirmed VTE, anticoagulation is the mainstay of treatment. However, patients with high-risk features at presentation may benefit from advanced reperfusion therapies such as thrombolysis and/or interventional approaches to reduce early mortality and/or long-term morbidity. The advent of direct oral anticoagulants has greatly simplified the treatment of VTE for most patients, with a persisting role for low molecular weight heparin and vitamin K antagonists in select patient groups. Following an initial 3 to 6 months of anticoagulation, those with major transient provoking factors can safely discontinue anticoagulation. Balancing the risk of recurrent VTE and bleeding risk is central to decisions regarding long-term anticoagulation, and patients should be included in shared decision-making. Assessment and recognition of common long-term complications such as postthrombotic syndrome and post-PE syndrome are also essential, given they are associated with significant adverse impact on long-term quality of life, with a significant risk of mortality associated with the less frequent complication of chronic thromboembolic pulmonary hypertension. This review provides a basic overview and framework for the diagnostic approach to deep vein thrombosis and PE, risk stratification of confirmed diagnoses, and management.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How we treat severe inherited antithrombin deficiency: lessons from cases homozygous for the Budapest 3 variant.","authors":"Carlos Bravo-Pérez, Javier Corral, Christelle Orlando, Vera Ignjatovic, Péter Ilonczai, Zsuzsanna Bereczky","doi":"10.1016/j.jtha.2025.01.015","DOIUrl":"10.1016/j.jtha.2025.01.015","url":null,"abstract":"<p><strong>Background: </strong>Antithrombin deficiency represents one of the most severe inherited thrombophilias. Albeit a rare disorder, available knowledge suggests that antithrombin deficiency is underestimated due to the limitations of current diagnostic algorithms. The high clinical variability of this patient population may be another cause of underdiagnosis. Heterozygous type I (quantitative) variants are normally associated with a severe thrombophilic phenotype, while heterozygous type II (qualitative) variants are heterogeneous, including heparin-binding site defects, which are mild/moderate and the most prevalent. Antithrombin Budapest 3 (p.Leu131Phe) is the most frequent type II/heparin-binding site deficiency in Europe, particularly in the Roma population, with a remarkable existence of homozygous subjects.</p><p><strong>Objectives: </strong>To determine the clinical features, diagnostic procedures, and management of patients with severe antithrombin deficiency, leveraging the study of cases homozygous for the antithrombin Budapest 3 variant.</p><p><strong>Methods: </strong>Patients were selected from 699 subjects with antithrombin deficiency and recruited over 25 years from reference centers in Spain, Belgium, and Hungary.</p><p><strong>Results: </strong>Guided by 2 illustrative cases with homozygous antithrombin Budapest 3, we report the spectrum and clinical management of patients with this disorder. These cases, with very low antithrombin activity (<20%) and juvenile and recurrent venous thromboembolism, recapitulate numerous issues that one might encounter when treating patients with antithrombin deficiency. In addition, special clinical scenarios for which no formal evidence-based guidelines exist might be found more frequently in these patients, including heparin resistance, vena cava anomalies, and obstetric complications.</p><p><strong>Conclusion: </strong>Expert proposals on the optimal management of these controversial areas, as well as future perspectives, are also formulated.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}