Seminars in thrombosis and hemostasis最新文献

{"title":"Laboratory Testing for ADAMTS13 for Thrombotic Thrombocytopenia Purpura and Beyond.","authors":"Emmanuel J Favaloro, Leonardo Pasalic, Giuseppe Lippi","doi":"10.1055/s-0044-1792003","DOIUrl":"10.1055/s-0044-1792003","url":null,"abstract":"<p><p>ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), also called von Willebrand factor (VWF) cleaving protease, acts as a moderator of VWF activity. ADAMTS13 cleaves VWF multimers, thereby reducing VWF activity in blood. When ADAMTS13 is absent (e.g., in patients with TTP [thrombotic thrombocytopenia purpura]), accumulation of VWF in plasma can occur, particularly as \"ultra-large\" VWF multimers, with this leading to adverse outcomes such as thrombosis. Relative ADAMTS13 deficiencies also occur in several other conditions, including secondary thrombotic microangiopathies (TMA), cancer, and with severe infections such as in COVID-19 (coronavirus disease 2019). These situations might therefore be accompanied with relative loss of ADAMTS13, thereby potentially also leading to pathological VWF accumulation, with this then generating a prothrombotic milieu, thus contributing to enhance the risk of thrombosis. Laboratory testing for ADAMTS13 can aid in the diagnosis of such disorders (i.e., TTP, TMA), and help guide their management, with testing now accomplished using various assays. As most presentations of TTP reflect an acquired condition due to anti-ADAMTS13 antibodies, there may also be a need to test for these, as this will also influence clinical management. We herein provide an overview of TTP, note other conditions in which low levels of ADAMTS13 may be present, and then detail laboratory testing for both ADAMTS13 and associated inhibitors.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"687-697"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522927","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":"Variable Performance of D-dimer Testing by Hemostasis Laboratories: The Australasian/Asia-Pacific Experience.","authors":"Emmanuel J Favaloro, Sandya Arunachalam, Elysse Dean","doi":"10.1055/s-0044-1781450","DOIUrl":"10.1055/s-0044-1781450","url":null,"abstract":"<p><p>D-dimers represent the breakdown products of fibrin. Thus, elevated plasma D-dimers will arise following a thrombotic event, such as a deep vein thrombosis or a pulmonary embolism, and therefore, a nonelevated D-dimer is used to effectively exclude such events. D-dimers are also elevated in a range of other conditions, for example, during disseminated intravascular coagulation. D-dimer levels may also be associated with prognostic value. For example, highly raised D-dimer levels can be associated with worsening clinical features in coronavirus disease 2019. Thus, D-dimer testing represents a commonly requested hemostasis test, often performed in 24/7 laboratories. Unfortunately, D-dimer testing is neither standardized nor harmonized across manufacturers or laboratories. Indeed, considering reporting units and the magnitude of units, up to 28 different combinations may be reported by laboratories. We provide updated findings for D-dimer testing in our geographic region, using recent data from the Royal College of Pathologists of Australasia Quality Assurance Programs, an international external quality assessment program, currently with over 450 participants in the D-dimer module. Data show a wide variety of assays in use and variable outcomes in reported numerical values when assessing proficiency samples. D-dimer testing mostly comprised reagents from three main manufacturing suppliers, with a small number of users of reagents from other manufacturers. Reported results showed important differences in numerical values for the same homogeneous tested samples when normalized to a single reporting unit (e.g., mg/L). Nevertheless, despite using different test reagents and reporting, most participants uniformly identified D-dimer values as below or above a \"detection\" cut-off for samples that were constructed to be below or above most cut-off values. As expected, mixed findings were reported for samples containing levels around expected cut-off values. We hope that our findings, reflecting on the heterogeneity of test reagents and test data, help improve diagnostic testing for D-dimer testing and facilitate harmonization and standardization, in the future.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"629-640"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013289","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":"Laboratory Testing for Fibrinogen Disorders: From Routine Investigations to Research Studies.","authors":"Anetta Undas","doi":"10.1055/s-0044-1787725","DOIUrl":"10.1055/s-0044-1787725","url":null,"abstract":"<p><p>Congenital and acquired fibrinogen disorders often have heterogeneous clinical phenotypes and are challenging from a laboratory perspective. Fibrinogen determination using the Clauss method remains the gold standard, while the reproducibility and significance of the thrombin time and the reptilase time are limited. Molecular testing for causative mutations in fibrinogen genes is now recommended to confirm the diagnosis of congenital fibrinogen disorders. Research assays are used to evaluate alterations to fibrin formation and properties of plasma and purified fibrinogen-derived clots, characterized by fiber thickness, the number of branches, and pore sizes. Fibrin clot permeability (permeation, porosity) using a hydrostatic pressure system represents the most commonly used method for evaluating fibrin network density. Reduced clot permeability, which denotes the reduced size of an average pore in the network, results in tighter fibrin networks, typically associated with impaired susceptibility to lysis, leading to a thrombotic tendency. Biophysical properties of fibrin clots are largely assessed using rheometry, with atomic force microscopy and nanorheology being increasingly used in disease states. Thromboelastography and thromboelastometry, a simple modification of rheometry, have been used, mainly in intensive care units, for more than 50 years. Given growing evidence for altered fibrin clot properties in diseases with elevated risk of venous and arterial thromboembolism and in some bleeding disorders, further work on standardization and validation of the assessment of fibrin clot characteristics is needed. This review summarizes the current methods used to evaluate fibrinogen abnormalities in both diagnostic and research laboratories.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"651-659"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420732","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":"Laboratory Diagnostics for Thrombosis and Hemostasis Testing-Part IV.","authors":"Kristi J Smock, Karen A Moffat","doi":"10.1055/s-0045-1809437","DOIUrl":"10.1055/s-0045-1809437","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":"51 6","pages":"627-628"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804741","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":"Resistance or Resilience? Hemostatic Balance in an FV Leiden Elite Athlete.","authors":"Ciro Miele, Cristina Mennitti, Alessandro Gentile, Mariella Calvanese, Luca Manfredi, Andrea Ruggiero, Immacolata Randa, Ferdinando Cirillo, Giovanni D'Alicandro, Nadia Tinto, Giulia Frisso, Cristina Mazzaccara, Olga Scudiero","doi":"10.1055/a-2681-6784","DOIUrl":"https://doi.org/10.1055/a-2681-6784","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144967304","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":"Transfusion-Dependent Thalassemia and Venous Thromboembolism Management: Position Statement from the Steering Committees of Hemostasis and Erythrocyte and Hemoglobinopathies Study Groups-Hellenic Society of Haematology.","authors":"Vasiliki Danilatou, Emmanouil Papadakis, Elias Kyriakou, Efrosyni Nomikou, Sophia Delicou, Fotios Girtovitis","doi":"10.1055/a-2669-7739","DOIUrl":"10.1055/a-2669-7739","url":null,"abstract":"<p><p>Venous thromboembolism is often underestimated in transfusion-dependent thalassemia (TDT) patients, as arterial thrombotic events are more commonly observed. Although therapeutic advancements have transformed this disease from a once-fatal childhood disease into a manageable chronic condition, some treatments may contribute to an increased risk of thrombosis. Additionally, the prolonged life expectancy of these patients further contributes to the overall thrombotic risk. Patients with thalassemia major present multiple challenges when considering anticoagulation therapy. The decision-making process is complicated by a delicate balance between thrombotic risk-driven by disease-related and treatment-associated factors-and potential bleeding tendencies, particularly in the presence of comorbid conditions such as liver dysfunction, hypersplenism, or thrombocytopenia. Therefore, ongoing assessment of both thrombotic and bleeding risk and the implementation of appropriate preventive strategies are essential to optimize patient outcomes. This document presents a consensus statement from the Steering Committee of the Hemostasis Working Group of the Hellenic Society of Hematology, offering guidance on thromboprophylaxis and anticoagulation management in adult TDT patients.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144744625","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":"Machine Learning in Venous Thromboembolism - Why and What Next?","authors":"Gerard Gurumurthy, Filip Kisiel, Lianna Reynolds, Will Thomas, Maha Othman, Deepa J Arachchillage, Jecko Thachil","doi":"10.1055/a-2669-7933","DOIUrl":"10.1055/a-2669-7933","url":null,"abstract":"<p><p>Venous thromboembolism (VTE) remains a leading cause of cardiovascular morbidity and mortality, despite advances in imaging and anticoagulation. VTE arises from diverse and overlapping risk factors, such as inherited thrombophilia, immobility, malignancy, surgery or trauma, pregnancy, hormonal therapy, obesity, chronic medical conditions (e.g., heart failure, inflammatory disease), and advancing age. Clinicians, therefore, face challenges in balancing the benefits of thromboprophylaxis against the bleeding risk. Existing clinical risk scores often exhibit only modest discrimination and calibration across heterogeneous patient populations. Machine learning (ML) has emerged as a promising tool to address these limitations. In imaging, convolutional neural networks and hybrid algorithms can detect VTE on CT pulmonary angiography with areas under the curves (AUCs) of 0.85 to 0.96. In surgical cohorts, gradient-boosting models outperform traditional risk scores, achieving AUCs between 0.70 and 0.80 in predicting postoperative VTE. In cancer-associated venous thrombosis, advanced ML models demonstrate AUCs between 0.68 and 0.82. However, concerns about bias and external validation persist. Bleeding risk prediction models remain challenging in extended anticoagulation settings, often matching conventional models. Predicting recurrent VTE using neural networks showed AUCs of 0.93 to 0.99 in initial studies. However, these lack transparency and prospective validation. Most ML models suffer from limited external validation, \"black box\" algorithms, and integration hurdles within clinical workflows. Future efforts should focus on standardized reporting (e.g., Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis [TRIPOD]-ML), transparent model interpretation, prospective impact assessments, and seamless incorporation into electronic health records to realize the full potential of ML in VTE.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883584","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":"Introducing the New Definition and Diagnostic Criteria of Disseminated Intravascular Coagulation Released by the International Society on Thrombosis and Haemostasis in 2025.","authors":"Toshiaki Iba, Cheryl L Maier, Ecaterina Scarlatescu, Jerrold H Levy","doi":"10.1055/a-2675-6068","DOIUrl":"10.1055/a-2675-6068","url":null,"abstract":"<p><p>In 2025, the International Society on Thrombosis and Haemostasis (ISTH) released updated definitions and diagnostic criteria for disseminated intravascular coagulation (DIC), reflecting advances in understanding its pathophysiology. DIC is now defined as an acquired, life-threatening condition involving systemic coagulation activation, impaired fibrinolysis, and endothelial injury. The revised framework emphasizes the condition's dynamic nature, progressing from preclinical abnormalities to overt clinical manifestations such as bleeding and organ dysfunction. A major innovation in the 2025 update is the phase-based classification of DIC: Pre-DIC, early-phase DIC, and overt DIC. Early-phase DIC-also referred to as subclinical or compensated DIC-is characterized by laboratory abnormalities preceding clinical symptoms. Overt DIC represents the advanced stage with clear evidence of coagulopathy and organ failure. Importantly, the new criteria are tailored to the underlying disease, such as sepsis, trauma, or malignancy. For example, the sepsis-induced coagulopathy score is now acknowledged as a tool for detecting early-phase DIC in septic patients. The overt DIC scoring system has been refined, including revised D-dimer thresholds: Levels >3× and >7 × , the upper normal limit now corresponds to 2 and 3 points, respectively. Platelet count, prothrombin time-international normalized ratio, and fibrinogen levels remain key indicators. The criteria also classify DIC into thrombotic and hemorrhagic phenotypes. Thrombotic DIC is marked by microvascular thrombosis and organ dysfunction, while hemorrhagic DIC is characterized by bleeding due to consumption of coagulation factors. By introducing clearer definitions and individualized approaches, these updates aim to enable earlier diagnosis and more effective management of DIC across clinical contexts.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883583","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":"Thrombocytopenia after Hematopoietic Stem Cell Transplantation in Pediatrics and Adults: A Narrative Review Including Etiology, Management, Monitoring, and Novel Therapies.","authors":"Amirali Kalantari, Zahra Karimizadeh, Leila Jafari, Maryam Behfar, Amir Ali Hamidieh","doi":"10.1055/a-2673-4266","DOIUrl":"10.1055/a-2673-4266","url":null,"abstract":"<p><p>Thrombocytopenia following hematopoietic stem cell transplantation (HSCT) is a common complication that is associated with a remarkable increase in morbidity and mortality. Post-HSCT thrombocytopenia is a multifactorial condition with several mechanisms, including reduced platelet production in bone marrow, immune-mediated platelet destruction, and consumptive thrombocytopenia. Graft-versus-host disease (GVHD), medications, infections, and autoimmune mechanisms are potential risk factors for post-HSCT thrombocytopenia. Management of post-HSCT thrombocytopenia primarily focuses on supportive care through platelet transfusions. Moreover, immunosuppressive agents are used to target immune-mediated mechanisms. Thrombopoietin receptor agonists and complement inhibitors are novel treatment options with promising results and fewer side effects. However, further research is essential to establish treatment protocols and improve patient care. In this review, we provide a better understanding of the pathophysiology and risk factors associated with post-HSCT thrombocytopenia for early detection and intervention, ultimately aiming to reduce complications.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765377","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":"COVID-19 and Anticoagulant Use: Did the Pandemic Push DOACs Ahead of Warfarin?","authors":"Bingwen Eugene Fan, Jia Hui Melissa Tan, Doreen Su-Yin Tan","doi":"10.1055/a-2667-6770","DOIUrl":"10.1055/a-2667-6770","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) pandemic introduced unprecedented disruptions to health care delivery, compelling rapid adaptations in anticoagulation management. Direct oral anticoagulants (DOACs), already displacing warfarin due to their convenience and reduced monitoring requirements, appeared well-positioned for broader adoption during pandemic-induced lockdowns. This commentary examines whether the pandemic catalyzed a meaningful shift in anticoagulant prescribing patterns from vitamin K antagonists (VKAs) to DOACs, drawing on data from the United Kingdom, Australia, the United States, Europe, and Asia. In the United Kingdom, national guidance led to an abrupt and large-scale switch to DOACs, with sustained changes postpandemic. In contrast, Australia and the United States exhibited continuity in preexisting trends, with modest, transient shifts that did not persist. Asian and European data revealed a gradual trajectory toward DOACs, likely driven by long-term policy and infrastructure rather than acute pandemic pressures. While no universal transformation occurred, the pandemic accentuated existing preferences and exposed system-level vulnerabilities in warfarin monitoring. The global experience suggests that the COVID-19 crisis served as a selective accelerant of DOACs adoption, where health care systems and policies facilitated change. As health systems prepare for future disruptions, equitable access to DOACs and investment in remote care infrastructure will be essential to ensuring continuity and safety in anticoagulation therapy.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732958","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}