Seminars in thrombosis and hemostasis最新文献

{"title":"Redefining Fibrinolytic Insufficiency in Sepsis-Associated DIC.","authors":"Toshiaki Iba, Julie Helms, Cheryl L Maier, Ian Roberts","doi":"10.1055/a-2840-5585","DOIUrl":"https://doi.org/10.1055/a-2840-5585","url":null,"abstract":"<p><p>Sepsis disrupts the physiological balance between coagulation and fibrinolysis, resulting in a state in which fibrin formation exceeds fibrin removal and drives microvascular thrombosis, organ failure, and mortality. Although an early burst of endothelial tissue-type plasminogen activator (t-PA) may transiently increase plasmin generation, this phase is rapidly eclipsed by sustained upregulation of plasminogen activator inhibitor-1 (PAI-1), dysregulated activation of thrombin-activatable fibrinolysis inhibitor, depletion of endogenous anticoagulants, and progressive endotheliopathy. Beyond inhibitor excess, emerging evidence indicates that a quantitative defect in plasminogen is a central contributor to fibrinolytic insufficiency. Neutrophil extracellular traps (NETs) contain elastase, which cleaves plasminogen into inactive fragments, reducing functional plasminogen availability and impairing fibrin-bound plasmin generation. When functional plasminogen falls below rate-limiting levels, fibrin surfaces cannot efficiently support plasmin formation, resulting in persistent microvascular fibrin deposition despite elevated D-dimer concentrations. This NET-plasminogen axis links immunothrombosis to the \"fibrinolytic insufficiency phenotype observed in sepsis-induced coagulopathy and overt disseminated intravascular coagulation (DIC).\" Clinically, hypofibrinolysis is characterized by high D-dimers, elevated PAI-1, reduced plasmin generation, and low fibrinolytic activity on viscoelastic testing. Multimodal assessment integrating biomarker panels and viscoelastic assays, including t-PA- or urokinase-challenged protocols, may improve risk stratification. Therapeutic strategies largely targeted coagulation; however, persistent hypofibrinolysis limits their effectiveness. Translational data demonstrate that plasminogen supplementation restores functional plasminogen levels and normalizes plasmin generation in septic patients and in experimental DIC, providing proof of concept for fibrinolysis-directed therapy. Future progress requires standardized definitions, functional fibrinolytic phenotyping, and phenotype-guided clinical trials to restore the coagulo-fibrinolytic balance in sepsis.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646294","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":"Thrombotic and Bleeding Complications in Myeloproliferative Neoplasms: An Integrated Clinical Perspective.","authors":"Omri Cohen, Martin H Ellis","doi":"10.1055/a-2836-0670","DOIUrl":"10.1055/a-2836-0670","url":null,"abstract":"<p><p>Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders characterized by elevated thrombotic and bleeding risk, and optimal risk stratification and management remain challenging. This review summarizes current evidence on the thrombotic complications in MPNs, including venous events (i.e., deep vein thrombosis, pulmonary embolism, and unusual site thrombosis), and arterial events (ischemic stroke, myocardial infarction, and peripheral arterial thrombosis), and the increased bleeding risk in these diseases. Mechanistically, JAK2-driven clonal hematopoiesis, elevated hematocrit, leukocytosis, platelet activation, endothelial dysfunction, and chronic inflammation interact to promote a pro-thrombotic state; conversely, extreme thrombocytosis, acquired von Willebrand syndrome, and anticoagulant/antiplatelet therapy contribute to bleeding risk. Clinically, thrombosis may precede MPN diagnosis, especially in unusual sites, and treatment should balance the risk of recurrent thrombosis against the risk of hemorrhagic complications. Antithrombotic strategies include low-dose aspirin, vitamin K antagonists, and direct oral anticoagulants, while cytoreductive therapy (hydroxyurea, anagrelide, interferon, and JAK inhibitors) is central for disease control as well as vascular risk reduction. Despite therapy, recurrence of thrombotic events and major bleeding persists, highlighting the need for optimized risk models and alternative therapeutic targets. Future research may focus on integrating molecular biomarkers, inflammation metrics, and vascular-specific endpoints to direct personalized preventive strategies.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487316","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":"Rebalanced hemostasis, bleeding and thrombosis in liver disease: a comprehensive review of pathophysiology, management and future perspectives.","authors":"Fynn Elvers, Ton Lisman","doi":"10.1055/a-2848-9427","DOIUrl":"https://doi.org/10.1055/a-2848-9427","url":null,"abstract":"<p><p>Patients with liver disease exhibit complex changes in the hemostatic system that are often presumed to drive bleeding and thrombosis. Historically, liver disease was considered a bleeding disorder based on thrombocytopenia, prolonged routine coagulation tests, and reports of fulminant bleeding. Present evidence, however, indicates that antihemostatic changes are compensated for by simultaneous prohemostatic changes, resulting in a rebalanced hemostatic system. Further hemostatic changes may be induced by liver disease progression and extrahepatic factors, such as systemic inflammation, acute kidney injury and cardiometabolic diseases. Despite extensive hemostatic changes in liver disease, current evidence does not consistently show that they increase bleeding risk, although this has been suggested repeatedly in published literature. Indeed, hemostatic changes appear largely unrelated to most bleeding complications, and specific thrombotic complications also appear unrelated to hemostatic changes. Major bleeding is common but predominantly reflects portal hypertension-related acute variceal bleeding and mechanical injury-related procedural bleeding. A proportion of bleedings, however, may be hemostasis-related, but the vast majority of such events do not require prohemostatic intervention. In contrast, a large proportion of thrombotic complications, including venous thromboembolism, portal vein thrombosis, and intrahepatic thrombosis, may in part be related to prohemostatic changes, although the role of hypercoagulability in portal vein thrombosis is increasingly questioned. Despite greater attention for thrombotic complications in liver disease, robust studies on optimal anticoagulant strategies are currently lacking. Studies evaluating the pharmacokinetics, pharmacodynamics, and efficacy for prevention of thrombosis and liver decompensation, of direct oral anticoagulants and factor XIa inhibitors are therefore urgently needed.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634192","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":"Lupus Anticoagulant-hypoprothrombinemia Syndrome: A Review Enriched by a New Particular Patient.","authors":"Doris Barcellona, Antonella Mameli, Roberta Montisci, Maria Filomena Ruberto, Lara Fenu, Francesco Marongiu","doi":"10.1055/a-2657-6291","DOIUrl":"10.1055/a-2657-6291","url":null,"abstract":"<p><p>Lupus anticoagulant-hypoprothrombinemia syndrome (LAHS) is a rare hemorrhagic disorder that should be differentiated from classical antiphospholipid syndrome. Literature review shows that LAHS may affect people at any age but approximately 40% are children younger than 10 years. Autoimmune and infectious diseases are the most frequent triggering causes, and the laboratory profile is characterized by a prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) with a mild to severe reduction in factor II levels. In more than half the patients, the other coagulation factors are normal, while anti-cardiolipin and anti-β2-glycoprotein I antibodies show a high titer. Lupus anticoagulant (LA) is positive in 100% of cases, as this represents a defining feature. The majority of patients have mucocutaneous bleeding events (44%); cerebral bleeding can occur in 10% of patients and other common bleeding sites are the gastrointestinal and genitourinary tracts. There is no standard treatment for LAHS. Supportive measures, such as fresh frozen plasma, packed red blood, and platelet transfusion, are frequently administered in association with steroids alone or in combination with intravenous immunoglobulin or cyclophosphamide, azathioprine, and rituximab. Death, recurrent bleeding, and thrombosis can occur in approximately 3, 13, and 14% of patients, respectively. Our patient was an old man with a myocardial infarction and a systemic infection from <i>Candida parapsilosis</i>. Thrombin generation and clot waveform analysis were performed before and after treatment. Thrombin generation better reflected the role of prothrombin, revealing that a factor II value of below around 15% can represent a risk for major bleeding. Treatment with methylprednisolone and three-factor human prothrombin complex concentrate allowed the patient to reach a complete recovery 1 month after initial diagnosis.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"304-314"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732959","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":"Coagulation Abnormalities Associated with COVID-19: A Narrative Review.","authors":"Massimo Franchini, Daniele Focosi, Pier Mannuccio Mannucci","doi":"10.1055/a-2619-2485","DOIUrl":"10.1055/a-2619-2485","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by severe acute respiratory disease coronavirus 2 (SARS-COV-2), has caused in the last 5 years a global pandemic of unprecedented scale in the modern era. Other than the typical respiratory symptoms, patients suffering from moderate to severe COVID-19 are at risk of developing a peculiar systemic coagulopathy, known as COVID-19-associated coagulopathy. In addition to a predominantly hypercoagulable state, COVID-19 patients may experience hemorrhagic complications triggered by the viral infection. The current knowledge on the underlying molecular mechanisms, the laboratory and clinical characteristics of coagulation abnormalities associated with COVID-19, along with their management, will be summarized in this narrative review.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"327-334"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132894","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":"Emicizumab in Acquired Hemophilia A: A Real-World Case Series with Patient-Level Outcome Analysis.","authors":"Ilenia Calcaterra, Carmine De Luca, Guido D'Errico, Ciro Miele, Chiara Caputo, Raffaele Russo, Paolo Conca, Ernesto Cimino, Anna Guida, Antonella Tufano, Matteo Di Minno","doi":"10.1055/a-2788-1642","DOIUrl":"10.1055/a-2788-1642","url":null,"abstract":"<p><p>Acquired Hemophilia A (AHA) is a rare bleeding disorder caused by factor VIII inhibitors. Standard therapies are limited by thrombotic risk and prolonged hospitalization. Emicizumab, approved for congenital Hemophilia A, has emerged as a potential alternative in AHA based on case reports and early clinical trial data. To evaluate the efficacy and safety of Emicizumab in AHA through a retrospective real-world case series and a systematic literature review with patient-level data analysis. We retrospectively analyzed five AHA cases treated with Emicizumab at two Italian centers and performed a PRISMA-compliant systematic review of published reports, extracting and analyzing patient-level data using Joanna Briggs Institute tools. In the real-world cohort, early Emicizumab use in five patients with high-titer inhibitors and severe bleeding led to rapid hemorrhagic control, early withdrawal of bypassing agents, and no thrombotic or adverse events. All five patients received immunosuppression, and inhibitor eradication was achieved in 60% of patients, but for 40% follow up is still ongoing. The literature review identified 24 patients from 18 publications. Early Emicizumab administration (at admission) was associated with reduced bleeding recurrence (0% vs. 56.3%), shorter in-hospital stay (median 23.5 days vs. 39 days), and lower bleeding-related mortality (0% vs. 12.5%) compared with delayed administration. Early Emicizumab initiation appears to be a safe and effective strategy for AHA management, particularly in fragile or high-risk populations. Its subcutaneous route, favorable safety profile, and ability to reduce hospitalization support its integration into first-line therapeutic algorithms. Further prospective studies are warranted to define.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"349-358"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985397","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":"Emicizumab in Acquired Hemophilia A: Benefits in Bleed Control, Safety, and Cost-Effectiveness.","authors":"Gerard Gurumurthy, Lianna Reynolds, Martin Scott, Elizabeth Davies, Charles Hay, Jecko Thachil","doi":"10.1055/a-2691-6232","DOIUrl":"10.1055/a-2691-6232","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"362-364"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030518","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":"Acquired Hemostasis Disorders.","authors":"Antonella Tufano, Massimo Franchini, Antonio Coppola","doi":"10.1055/a-2788-1844","DOIUrl":"https://doi.org/10.1055/a-2788-1844","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":"52 3","pages":"277-279"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390782","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":"Coagulation Abnormalities in Chronic Liver Disease.","authors":"Massimo Franchini, Pier Mannuccio Mannucci","doi":"10.1055/a-2531-4712","DOIUrl":"10.1055/a-2531-4712","url":null,"abstract":"<p><p>Chronic liver disease is a frequently encountered disorder and a major concern worldwide with a complex pathophysiology, which often affects the hemostatic system. Such alterations, which affect both primary and secondary hemostasis, are heterogenous, including prohemorrhagic (i.e., decreased coagulation factors, increased fibrinolysis, thrombocytopenia, and platelet dysfunction) and prothrombotic (i.e., decreased natural anticoagulants) changes. As a consequence of this unstable balance, patients with liver cirrhosis may experience both hemorrhagic complications and venous thromboembolic events, which are often unpredictable and whose management is particularly challenging for clinicians. This narrative review will address the most recent advances in the pathophysiology of key derangements of hemostasis in patients with chronic liver disease, focusing on their clinical implications and management.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"335-341"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190516","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":"Early Emicizumab Treatment in Acquired Hemophilia A: Impact on Bypassing Agent Use and Length of Hospitalization in an Australian Single-Center Cohort.","authors":"Gianna Pastore, Jeremy Robertson, Sally Campbell, Jane Mason","doi":"10.1055/a-2622-3483","DOIUrl":"10.1055/a-2622-3483","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"359-361"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317851","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}