Seminars in thrombosis and hemostasis最新文献

{"title":"Autoantibodies in Autoimmune Coagulation Factor Deficiencies: A Review of Inhibitory and Clearance-Accelerating Mechanisms from Japanese practice.","authors":"Akitada Ichinose","doi":"10.1055/a-2576-5019","DOIUrl":"https://doi.org/10.1055/a-2576-5019","url":null,"abstract":"<p><p>Autoimmune acquired coagulation factor deficiency (AiCFD) represents a rare coagulation disorder that primarily affects older people and sometimes causes fatal bleeding; therefore, clinicians need to consider this when encountering patients with unexplained bleeding. AiCFD is caused by the production of autoantibodies against one's own coagulation factor, which markedly inhibit its function, or accelerate its clearance from plasma, resulting in hemostatic failure. The plasma of affected patients shows various abnormal findings, because anti-coagulation factor-autoantibodies are polyclonal, and each clone has differing properties. First, inhibitor type autoantibodies target the functional sites of coagulation factors, thereby considerably reducing their activity. Second, clearance-accelerating autoantibodies bind to non-functional sites and cause rapid removal of coagulation factors from the blood, thereby reducing their levels (and their activity in parallel). Third, mixed type autoantibodies (inhibitory clearance-accelerating) substantially reduce coagulation factor activity and level to various degrees. Most anti-coagulation factor-autoantibodies are inhibitory clearance-accelerating types, although pure inhibitor types remain clinically significant; however, the pure clearance-accelerating type appears to be rare, possibly because the autoantibody is not detected unless it exceeds the level of the target coagulation factor (pseudo-autoantibody negative). Moreover, anti-factor XIII-autoantibodies are particularly complex, as they interfere with the A subunit (Aa type), its activated form (Ab type), and/or the B subunit (B type). Of the three types, Aa type anti-factor XIII-autoantibodies contain a mixture of different inhibitor type autoantibodies in various ratios in plasma, resulting in an extremely diverse range of test findings. Therefore, care must be taken when diagnosing and assessing the efficacy of treatment.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812261","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":"Thrombin Generation Assays: What are the Current Clinical Applications?","authors":"Armando Tripodi, Marigrazia Clerici, Erica Scalambrino, Flora Peyvandi","doi":"10.1055/s-0045-1807261","DOIUrl":"https://doi.org/10.1055/s-0045-1807261","url":null,"abstract":"<p><p>The thrombin generation assay (TGA), originally developed by McFarlane and Biggs in 1956, was modified in the 2000s by Hemker and coworkers. TGA aims to monitor the continuous generation of thrombin upon activation of coagulation in plasma by the addition of such triggers as small amounts of tissue factor, synthetic phospholipids, and calcium chloride. TGA is sensitive to hypo- and hypercoagulability and is affected by prohemostatic as well as antithrombotic drugs. The review of the current literature shows that TGA is mainly used to investigate conditions characterized by hypo- as well as hypercoagulability and as a laboratory tool to elucidate coagulation mechanisms that are not yet completely understood. This article aims to overview the value and limits of current procedures for TGA for the investigation of hemostasis.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804207","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":"Factor Inhibitor Testing: An Update from Australasia/Asia-Pacific.","authors":"Emmanuel J Favaloro, Sandya Arunachalam","doi":"10.1055/a-2546-0441","DOIUrl":"10.1055/a-2546-0441","url":null,"abstract":"<p><p>Factor VIII (FVIII) inhibitors represent antibodies that develop against coagulation FVIII and reduce FVIII functional activity. FVIII inhibitors may develop in patients with congenital hemophilia A (CHA) in response to infused FVIII (allo-antibodies) or in patients without CHA in a variety of situations (auto-antibodies; acquired hemophilia A). We report updated findings for FVIII inhibitor testing in our geographic region using recent data (testing for the past 5 years; 2020-2024 inclusive) from the RCPAQAP (Royal College of Pathologists of Australasia Quality Assurance Program), an international external quality assessment (EQA) program, with over 80 enrolments for the FVIII inhibitor module. Four samples are assessed each year, with these comprising both FVIII inhibitor negative samples and FVIII inhibitor positive samples with various inhibitor titers. This EQA data largely evidences favorable findings in FVIII inhibitor testing in our jurisdiction, with >99% of test results interpreted correctly by participants for the presence (\"detected\") or absence (\"not detected\") of FVIII inhibitors in assessed samples. Moreover, most errors in interpretation appear to be transcription or data entry errors rather than analytic errors. The coefficient of variation (CV) values for FVIII inhibitor samples were moderately high, ranging from 25 to 40%, irrespective of the inhibitor titer (range: 3-64 Bethesda units [BU]/mL) or the method (i.e., Bethesda vs. Nijmegen). In conclusion, most laboratories were able to correctly identify the presence versus absence of FVIII inhibitors, although laboratory-reported titers varied moderately.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524343","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":"Hemostatic and inflammatory biomarkers are associated with functional limitations after venous thromboembolism: A prospective cohort study.","authors":"Daniel Steiner, Stephan Nopp, Timothy Hoberstorfer, Oliver Schlager, Ingrid Pabinger, Benedikt Weber, Cihan Ay","doi":"10.1055/a-2574-8775","DOIUrl":"https://doi.org/10.1055/a-2574-8775","url":null,"abstract":"<p><p>Functional limitations often persist in patients with venous thromboembolism (VTE). The relevance of biomarkers for these outcomes remains unexplored. Therefore, we aimed to investigate the association of hemostatic, inflammatory, and cardiovascular biomarkers with functional limitations three months after VTE. We conducted a prospective cohort study, including patients with acute VTE within 21 days of diagnosis. Biomarkers levels (D-dimer, fibrinogen, factor VIII (FVIII), von Willebrand factor antigen (VWF), C-reactive protein (CRP), troponin T, N-terminal pro b-type natriuretic peptide (proBNP)) were measured at inclusion and three months. Functional limitations at three months were evaluated with the post-VTE functional status scale (0-4, higher indicating more limitations). The association of biomarkers with functional limitations was assessed with proportional odds models adjusted for confounders. Furthermore, we evaluated the AUC-ROC for the presence of slight-to-severe functional limitations. Overall, we included 290 patients (41.4% women) with a median age of 54.9 years (IQR: 43.1-64.2). D-dimer, fibrinogen, FVIII, VWF, and CRP measured at inclusion were independently associated with functional limitations at three months. VWF showed the most favorable AUC-ROC (0.62, 95%CI, 0.55-0.69). In patients with pulmonary embolism, troponin T and proBNP were not associated with functional limitations. At three-month follow-up, D-dimer was the only biomarker independently associated with functional limitations, yielding an AUC of 0.62 (96%CI, 0.55-0.69). In conclusion, we identified biomarkers independently associated with functional limitations three months after VTE. Our results indicate a role of these biomarkers in early identification of patients at risk of persistent functional limitations and suggest their involvement in the underlying mechanisms.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788701","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":"Comments to the International Council for Standardization in Hematology Guidance for New Lot Verification of Coagulation Reagents, Calibrators, and Controls.","authors":"Marc Thelen, Marith van Schrojenstein Lantman, Anne Stavelin, Tze Ping Loh","doi":"10.1055/a-2572-1299","DOIUrl":"https://doi.org/10.1055/a-2572-1299","url":null,"abstract":"<p><p>N.A.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773308","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":"Pharmacotherapy for Venous Thromboprophylaxis following Total Hip or Knee Arthroplasty: A Systematic Review and Network Meta-analysis.","authors":"Bryan Song Jun Yong, Ryan Ruiyang Ling, Ruiqi Li, Jane Wenjin Poh, Chuen Seng Tan, Sean Wei Loong Ho, Bram Rochwerg, Roopen Arya, Kollengode Ramanathan, Bingwen Eugene Fan","doi":"10.1055/s-0044-1787996","DOIUrl":"10.1055/s-0044-1787996","url":null,"abstract":"<p><p>The optimal pharmacological prophylaxis for venous thromboembolism (VTE) after hip or knee arthroplasty is uncertain. We conducted a systematic review and network meta-analysis to compare the efficacy and safety of various medications. We searched multiple databases for randomized clinical trials (RCTs) comparing medications (including factor Xa inhibitors, factor IIa inhibitor, warfarin, unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], aspirin, pentasaccharide) for VTE prophylaxis post-arthroplasty. Outcomes included any postoperative VTE identified with screening, major bleeding, and death. We used LMWH as the main comparator for analysis and performed trial sequential analysis (TSA) for each pairwise comparison. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessments, Developments and Evaluations). We analyzed 70 RCTs (55,841 participants). Factor Xa inhibitors decreased postoperative VTE significantly compared with LMWH (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.44-0.68, high certainty). Pentasaccharides probably reduce VTE (OR: 0.61, 95% CI: 0.36-1.02, moderate certainty), while the factor IIa inhibitor dabigatran may reduce VTE (OR: 0.75, 95% CI: 0.40-1.42, low certainty). UFH probably increases VTE compared with LMWH (OR: 1.31, 95% CI: 0.91-1.89, moderate certainty), and other agents like warfarin, aspirin, placebo, and usual care without thromboprophylaxis increase VTE (high certainty). Factor Xa inhibitors may not significantly affect major bleeding compared with LMWH (OR: 1.06, 95% CI: 0.81-1.39, low certainty). No medications had a notable effect on mortality compared with LMWH (very low certainty). TSA suggests sufficient evidence for the benefit of factor Xa inhibitors over LMWH for VTE prevention. Compared with LMWH and aspirin, factor Xa inhibitors are associated with reduced VTE after hip or knee arthroplasty, without an increase in bleeding and likely no impact on mortality.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"290-300"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477365","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":"Intravenous Direct Thrombin Inhibitors for Acute Venous Thromboembolism or Heparin-Induced Thrombocytopenia with Thrombosis in Children: A Systematic Review of the Literature.","authors":"Amy L Kiskaddon, Josh Branstetter, Pam Williams, Vera Ignjatovic, Amanda Memken, Kristopher Wilhoit, Neil A Goldenberg","doi":"10.1055/s-0044-1791534","DOIUrl":"10.1055/s-0044-1791534","url":null,"abstract":"<p><p>Intravenous direct thrombin inhibitors (DTIs) are used for thromboembolic disorders. This systematic review aims to characterize intravenous DTI agents, dosing, monitoring strategies (or use), bleeding, and mortality, in pediatric patients with acute venous thromboembolism (VTE) or heparin-induced thrombocytopenia with thrombosis (HITT). MEDLINE, Embase, and Cochrane's CENTRAL were searched from inception through July 2023. Case series, retrospective studies, and prospective studies providing per-patient or summary data for patients < 18 years of age with VTE or HITT treated with an intravenous DTI were included. Selection and data extraction were conducted independently by two reviewers. Sixteen studies (7 case reports, 1 case series, 5 retrospective studies, 3 prospective studies) with 85 patients were included. Target conditions included acute VTE in 54 (64%) and HITT in 31 (36%) patients. Bivalirudin, argatroban, and lepirudin were used in 52 (61%), 27 (32%), and 6 (7%) patients, respectively. Fifty-two (61%) patients received a bolus dose, and weighted mean infusion rates for bivalirudin, argatroban, and lepirudin were 0.2 mg/kg/hr, 1.2 mcg/kg/min, and 0.15 mg/kg/hr, respectively. The activated partial thromboplastin time was utilized for monitoring in 82 (96%) patients. Complete or partial thrombus resolution was reported in 53 (62%) patients, mortality in 6 (7%) patients, and bleeding complications in 14 (16%) patients. In this systematic review involving 85 pediatric patients treated with an intravenous DTI for acute VTE or HITT, bivalirudin was the most commonly utilized agent, with a rate of resolution over 60% despite a high acuity in the population studied. Prospective collaborative studies are warranted to establish optimal dosing and further characterize VTE and bleeding outcomes.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"329-334"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393065","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":"Mendelian Randomization Provides No Evidence for the Bidirectional Relationship between Type 2 Diabetes and Venous Thromboembolism in East Asians and African Americans.","authors":"Jiawen Lu, Zhenqian Wang","doi":"10.1055/s-0044-1788568","DOIUrl":"10.1055/s-0044-1788568","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"348-350"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727736","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":"Impact of hematocrit on coagulation measured by rotational thromboelastometry in healthy subjects and patients with polycythemia.","authors":"Marie Martin, Elie Nader, Hamdi Rezigue, Yesim Dargaud, Celine Renoux, Philippe Joly, Mael Heiblig, Christophe Nougier, Philippe Connes","doi":"10.1055/a-2570-4455","DOIUrl":"https://doi.org/10.1055/a-2570-4455","url":null,"abstract":"<p><p>Thrombotic and cardiovascular events are among the leading causes of death for patients with polycythemia, more specifically for those with primary origin. It has been suggested that the high hematocrit would favor hypercoagulability. However, the impact of hematocrit on coagulation in patients with polycythemia has not been investigated so far. The aim of our study was to compare the coagulation profiles of healthy subjects and patients with polycythemia, and to evaluate the in-vitro impact of hematocrit on coagulation. Blood from healthy individuals (N=100 for blood viscosity; N=19 for coagulation) and patients with primary/secondary polycythemia (N=29 for blood viscosity; N=20 for coagulation) was used to perform measurements at native hematocrit. The impact of hematocrit modulation (20% vs 50%) on coagulation was tested in-vitro in 9 healthy subjects and 19 patients with polycythemia. Blood viscosity was measured by viscosimetry and coagulation and fibrinolysis by rotational thromboelastometry. In patients with polycythemia, hematocrit and blood viscosity were higher, clotting time was prolonged and clot lysis was faster compared to healthy individuals. Our in-vitro results showed that the clotting time was faster and the clot firmness higher at 20% vs 50% hematocrit for both populations, without any difference between the two populations at a given hematocrit. Our findings suggest that the interpretation of thromboelastometry results should be approached with caution in patients with high hematocrit. The in-vivo hypercoagulable state of patients with polycythemia is probably the consequence of changes in hemodynamic conditions attributed to blood hyper-viscosity, that may promote venous stasis and platelet margination.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764951","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":"Comprehensive Mendelian Randomization Analysis of Smoking and Its Effects on Venous Thromboembolism.","authors":"Yuhong Li, Ling Tong, Youqian Zhang, Birun Huang, Liping Zhu","doi":"10.1055/s-0044-1800980","DOIUrl":"10.1055/s-0044-1800980","url":null,"abstract":"<p><p>An increasing number of Mendelian randomization (MR) studies have evaluated the causal link between smoking and venous thromboembolism (VTE). However, previous studies often rely on single genetic variants related to smoking quantity and exhibit various other shortcomings, making them prone to pleiotropy and potentially leading to imprecise causal estimates. Thus, the deeper causal mechanisms remain largely unexplored. This MR study reassessed the causal relationship between smoking and VTE, including its subtypes-deep vein thrombosis (DVT) and pulmonary embolism (PE). Data on VTE were sourced from the FinnGen consortium with nonoverlapping sample sizes. The smoking phenotypes analyzed included smoking initiation, lifetime smoking, the number of cigarettes smoked per day by both current and former smokers (CigDay), and total pack-years of smoking in adulthood. The primary analytical method was inverse-variance-weighted (IVW), supplemented by multiple verification methods to ensure robust results. Statistical rigor was ensured through LDtrait pruning and Steiger filtering for reverse causation, with comprehensive sensitivity analyses including RadialMR confirming the findings' robustness. After Bonferroni correction, this study demonstrates significant causal evidence linking lifetime smoking with the incidence of VTE (odds ratio [OR]_IVW = 1.50, 95% confidence interval [CI] 1.21-1.85, <i>p</i> = 1.75 × 10^-4) and PE (OR_IVW = 1.69, 95% CI 1.25-2.28, <i>p</i> = 6.55 × 10^-4), and suggestive evidence with DVT, consistent in direction with previous studies but showing considerable differences in effect sizes and significance. Additionally, CigDay (past and current) increases the risks of VTE and DVT, while no causal link was found between smoking initiation and VTE or its subtypes (<i>p</i> < 0.05), both directly contradicting previous conclusions. Furthermore, our study is the first to suggest a causal link between pack-years and an increased risk of VTE. This MR study employed rigorous statistical pruning of its instrumental variables, using the most comprehensive smoking phenotype to date. It successfully mitigated biases such as winner's curse, yielding causal effect results distinct from previous studies.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"279-289"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847599","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}