Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Markers for platelet function testing by flow cytometry: where are we now? A clinical perspective","authors":"Benjamin E.J. Spurgeon","doi":"10.1016/j.rpth.2026.103452","DOIUrl":"10.1016/j.rpth.2026.103452","url":null,"abstract":"<div><div>Flow cytometry is transforming platelet function testing by offering high sensitivity, low sample requirements, and compatibility with thrombocytopenic and pediatric specimens. In contrast to light transmission aggregometry, it enables multiparameter analysis in whole blood, allowing detailed characterization of platelet activation, secretion, and procoagulant function. Current evidence indicates that a carefully selected panel of validated markers provides the most clinically actionable information for diagnosis and patient management. When integrated with clinical context, complementary laboratory data, and reproducible assay design, these readouts offer a pathway toward more accessible, practical, and widely implementable platelet testing, bridging the gap between specialized research assays and standard clinical practice.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103452"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147745139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durability of efficacy, safety, and quality of life 5 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A: final phase 3 GENEr8-1 trial results","authors":"Andrew D. Leavitt ,&nbsp;Johnny Mahlangu ,&nbsp;Priyanka Raheja ,&nbsp;Emily Symington ,&nbsp;Doris V. Quon ,&nbsp;Adam Giermasz ,&nbsp;Gili Kenet ,&nbsp;Gillian Lowe ,&nbsp;Nigel S. Key ,&nbsp;Carolyn M. Millar ,&nbsp;Steven W. Pipe ,&nbsp;Sheng-Chieh Chou ,&nbsp;Robert Klamroth ,&nbsp;Jane Mason ,&nbsp;Hervé Chambost ,&nbsp;Flora Peyvandi ,&nbsp;Elaine Majerus ,&nbsp;Dominic Pepperell ,&nbsp;Chee Wee Tan ,&nbsp;Hua Yu ,&nbsp;Margareth C. Ozelo","doi":"10.1016/j.rpth.2026.103416","DOIUrl":"10.1016/j.rpth.2026.103416","url":null,"abstract":"<div><h3>Background</h3><div>Valoctocogene roxaparvovec, a gene therapy for severe hemophilia A, enables endogenous factor VIII (FVIII) expression and confers bleed control.</div></div><div><h3>Objectives</h3><div>To present the final 5-year efficacy and safety results from the phase 3 GENEr8-1 trial.</div></div><div><h3>Methods</h3><div>Adult men (<em>N</em> = 134) with severe hemophilia A without inhibitors who were using FVIII prophylaxis received one 6 × 10¹³ vg/kg infusion of valoctocogene roxaparvovec. End points included annualized bleeding rate (ABR), FVIII infusion rate, FVIII activity, Haemophilia-Specific Quality of Life Questionnaire for Adults, adverse events, and immunosuppressant use.</div></div><div><h3>Results</h3><div>Median follow-up was 261.1 weeks; 128 of 134 participants completed the study. For the 112 participants who enrolled from a previous noninterventional study (rollover population), mean ABR for treated bleeds declined by 83.3% (<em>P</em> &lt; .0001), mean FVIII infusion rate declined by 94.9% (<em>P</em> &lt; .0001), and mean ABR for all bleeds declined by 78.1% in the 5-year efficacy evaluation period vs baseline. In 132 modified intention-to-treat participants, mean and median FVIII activity at week 260 was 13.7 and 6.2 IU/dL, respectively (chromogenic assay). In year 5, 77.8% of rollover participants had 0 treated bleeds. One participant resumed prophylaxis since the 4-year data cutoff (25/134 across all follow-up). Haemophilia-Specific Quality of Life Questionnaire for Adults total score was improved from baseline at year 5. In year 5, alanine aminotransferase elevations occurred in 51 of 129 participants who entered year 5. Immunosuppressants were not used to manage them. No serious treatment-related adverse events occurred after year 1.</div></div><div><h3>Conclusion</h3><div>Valoctocogene roxaparvovec provides durable hemostatic efficacy, FVIII activity, and improved health-related quality of life for ≥5 years, with no new safety signals.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103416"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147750613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors for venous thromboembolism in sickle cell disease","authors":"Neha Bhasin ,&nbsp;Li Zhang ,&nbsp;Ayotola Ajayi ,&nbsp;Seva Patel ,&nbsp;Taylor Imai ,&nbsp;Shreya Agarwal","doi":"10.1016/j.rpth.2026.103454","DOIUrl":"10.1016/j.rpth.2026.103454","url":null,"abstract":"<div><h3>Background</h3><div>Individuals with sickle cell disease (SCD) have a high risk for venous thromboembolism (VTE).</div></div><div><h3>Objectives</h3><div>To determine the associated risk factors and recurrence rate of VTE in SCD.</div></div><div><h3>Methods</h3><div>We performed a retrospective review of 719 individuals with SCD followed at our institution between 2013 and 2023 and compared those who developed VTE with those who did not.</div></div><div><h3>Results</h3><div>Of the 719 patients reviewed, 64 (8.9%) patients had 71 VTEs during the study period; 28% of the VTE events were pulmonary embolism and 61% were deep vein thrombosis. The odds ratio (OR) for developing a VTE was 164 (<em>P</em> &lt; .001) for patients with a history of VTE, and the VTE recurrence rate was 31% during the study period. In addition, a history of stroke (OR, 39.8; <em>P</em> &lt; .001) and a record of 6 or more hospitalizations in a 12-month period (OR, 15.5; <em>P</em> &lt; .001) were significant risk factors for VTE in SCD. Other risk factors included smoking (OR, 7.2; <em>P</em> &lt; .001), presence of a central venous catheter (OR, 6.9; <em>P</em> &lt; .001), and use of hormonal therapy (OR, 9.6; <em>P</em> &lt; .001).</div></div><div><h3>Conclusion</h3><div>We conclude that the risk of VTE in SCD is associated with a history of VTE or stroke, increased health care utilization, use of CVCs, hormonal therapies, and smoking. The high VTE recurrence rate in this study suggests a need to better prevent and treat VTEs in individuals with SCD.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103454"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147712880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaption of the plasmin generation assay to enhance sensitivity to plasminogen activator inhibitor-1 and establishment of sex-specific reference values in human plasma","authors":"Ilaria De Simone ,&nbsp;Kieran Pocknell ,&nbsp;Samia Tufaha ,&nbsp;Joke Konings ,&nbsp;Mark Roest ,&nbsp;Alisa S. Wolberg ,&nbsp;Claire S. Whyte ,&nbsp;Nicola J. Mutch ,&nbsp;Bas de Laat ,&nbsp;Dana Huskens","doi":"10.1016/j.rpth.2026.103435","DOIUrl":"10.1016/j.rpth.2026.103435","url":null,"abstract":"<div><h3>Background</h3><div>Pharmacologic modifiers of fibrinolysis are used to modulate bleeding and thrombosis. Characterization of a sensitive plasmin generation (PG) assay to identify abnormal fibrinolytic states and monitor antifibrinolytic medication may improve clinical care.</div></div><div><h3>Objectives</h3><div>To establish reference values of PG parameters, investigate sex-related differences, and study different regulators of fibrinolysis, using a PG assay.</div></div><div><h3>Methods</h3><div>PG was assessed in plasma of 130 healthy individuals, normal pooled plasma, or factor-deficient plasma, using tissue factor or Russell viper venom-factor (F)X activator, with tissue plasminogen activator or the novel antifibrin urokinase plasminogen activator.</div></div><div><h3>Results</h3><div>Reference values for PG parameters were established in plasma from healthy individuals. No PG was observed in plasminogen- or fibrinogen-deficient plasma. Thrombomodulin (TM), α₂-antiplasmin, and tranexamic acid reduced PG. Inhibitory effects of TM in PG were counteracted using carboxypeptidase inhibitor, an inhibitor specific to active thrombin-activatable fibrinolysis inhibitor, confirming a role for thrombin-activatable fibrinolysis inhibitor and TM in modulating PG. Although the PG assay triggered with tissue plasminogen activator was insensitive to plasminogen activator inhibitor-1, it became sensitive to it when induced with antifibrin urokinase plasminogen activator. PG measurements in plasma of healthy individuals showed elevated PG levels in 11 of 13 female healthy donors taking oral contraceptives and an increased resistance to TM in females compared with that in males.</div></div><div><h3>Conclusion</h3><div>The PG assay is a specific and efficient tool to assess modulators of fibrinolysis and to study sex-related differences and has potential as a clinical tool to identify abnormal fibrinolytic profiles in patients and monitor antifibrinolytic drugs, such as tranexamic acid.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103435"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147803603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired thrombin generation as a reproducible feature of bleeding disorder of unknown cause","authors":"Tim Dreier ,&nbsp;Dino Mehic ,&nbsp;Justin Oosterlee ,&nbsp;Helmut Haslacher ,&nbsp;Cihan Ay ,&nbsp;Ingrid Pabinger ,&nbsp;Johanna Gebhart","doi":"10.1016/j.rpth.2026.103451","DOIUrl":"10.1016/j.rpth.2026.103451","url":null,"abstract":"<div><h3>Background</h3><div>Thrombin generation (TG) has previously been investigated in patients with bleeding disorder of unknown cause (BDUC) with discrepant results.</div></div><div><h3>Objective</h3><div>To investigate whether previously reported impairments of TG in BDUC patients can be resproduced using a automated TG analysed at different tissue factor concentrations.</div></div><div><h3>Methods</h3><div>In this case–control cohort study, TG was measured in patients with BDUC and age- and sex-matched healthy controls using the fully automated Ceveron S100 assay with 2 trigger reagents: reagent B (RB; very low tissue factor concentration) and reagent C-low (RC; low tissue factor concentration).</div></div><div><h3>Results</h3><div>In total, 62 patients and 22 controls were analyzed. In both reagents, patients compared with healthy controls had longer time to peak (RB: 16.2 vs 12.8 seconds; RC-low: 10.3 vs 8.5 seconds; <em>P</em> &lt; .001), lower peak thrombin (RB: 209.0 vs 300.7 nM; <em>P</em> &lt; .001; RC-low: 243.6 vs 299.2 nM; <em>P</em> = .011), and lastly a lower velocity index (RB: 25.6 vs 45.9 nM/min; <em>P</em> &lt; .001; RC-low: 34.6 vs 54.3 nM/min; <em>P</em> = .001). The lag time was only significantly prolonged in patients in RB (7.6 vs 6.1 seconds; <em>P</em> &lt; .001), but not with RC-low (3.2 vs 3.0 seconds; <em>P</em> = .403), as was the area under the curve (RB: 2776.9 vs 3276.3 nM × min; <em>P</em> &lt; .001; RC-low: 2824.7 vs 2842.7 nM × min; <em>P</em> = .072). Crossvalidated receiver operating characteristic analysis showed an area under the curve of 0.74 (95% CI, 0.62-0.86) for RB and 0.76 (95% CI, 0.65-0.87) for RC-low. However, there was no association between the bleeding score and any TG parameters after adjustment for factor [F]VIII and FIX activity.</div></div><div><h3>Conclusion</h3><div>This study highlights the reproducibility of impaired TG in patients with BDUC. Given that BDUC pathophysiology remains largely unknown, these findings suggest impaired TG may represent a common underlying feature of BDUC and underscore the need for further validation in independent cohorts and clinical settings.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103451"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147712441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unmet health care needs in immune thrombotic thrombocytopenic purpura survivors","authors":"Charlotte M. Story ,&nbsp;Jenna Brown ,&nbsp;Clare Martin ,&nbsp;Shruti Chaturvedi","doi":"10.1016/j.rpth.2026.103461","DOIUrl":"10.1016/j.rpth.2026.103461","url":null,"abstract":"<div><h3>Background</h3><div>Immune thrombotic thrombocytopenic purpura (iTTP) is a rare thrombotic microangioathy episodic life-threatening thrombotic microangiopathy. Survivors of iTTP have high rates of chronic morbidities in remission such as depression, cognitive impairment, stroke, and increased cardiovascular mortality. Careful multidisciplinary management during clinical remission is needed to monitor for relapse and manage comorbidities, but this may not be universally available.</div></div><div><h3>Objectives</h3><div>To identify gaps in the outpatient care of iTTP survivors.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional survey-based study. The questionnaire included demographic information, disease-specific information, treatment-specific information, and the Healthcare Access and Utilization Survey developed by the National Institutes of Health All of Us Research Program.</div></div><div><h3>Results</h3><div>A total of 281 participants responded to the survey. Median age was 47 years (IQR, 34–60 years). Most respondents were women (255/278, 91.7%), White (206/281, 73.7%), and highly educated with 215 of 263 (81.7%) reporting some college or further education. A quarter of respondents, 67 of 247 (27.1%), had not seen a hematologist in the past year, and 48 of 247 (19.4%) had not seen a primary care provider. Additionally, 45 of 279 (16.1%) reported not having an iTTP doctor. Laboratory monitoring was performed every 6 months or less frequently in 38% of respondents. Treatment for relapse prevention was not discussed with 54.8%. While 82.7% self-reported mental health disturbance after iTTP diagnosis, 30.4% had been referred to a mental health professional.</div></div><div><h3>Conclusion</h3><div>In this United States-based cohort, despite high rates of medical and psychiatric comorbidities, only a minority reported high-quality relapse-prevention care. There were high rates of mental health disturbances after iTTP diagnosis but limited access to mental health care.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103461"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147859625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antithrombotic therapy at the end-of-life—continue or stop?","authors":"Gerard Gurumurthy ,&nbsp;Naisthika Kumar ,&nbsp;Lianna Reynolds ,&nbsp;Biddy Bassam ,&nbsp;Marc Carrier ,&nbsp;Simon Noble ,&nbsp;Alok A. Khorana ,&nbsp;Jecko Thachil","doi":"10.1016/j.rpth.2026.103459","DOIUrl":"10.1016/j.rpth.2026.103459","url":null,"abstract":"<div><div>Antithrombotics at the end-of-life pose a clinical challenge where indication-specific time-to-benefit, bleeding risk, and patient priorities must be reconciled over short prognostic horizons. In this review of the literature, we found that a substantial number of individuals remain on anticoagulants and antiplatelet therapy till the point of death. Prospective ultrasound surveillance studies show a high baseline incidence of asymptomatic proximal deep vein thrombosis at admission but a low short-term incidence of new events during typical hospice stays. Additionally, large home palliative cohorts suggest that deprescribing anticoagulants does not increase clinical thrombosis and may reduce bleeding and facilitate home death. Bleeding on antithrombotics is also common in the last months of life. Clinically relevant bleeding occurs in up to 1 in 10, and fatal hemorrhage has been reported. Cancer-specific factors, chronic or end-stage kidney disease, cytopenias, and drug interactions heighten the risks. Where anticoagulation is pursued, the choice of agent and route should reflect swallowing, nutrition, renal or hepatic function, monitoring capacity, and reversal intent. Structured, shared decision making and proactive deprescribing when benefits no longer outweigh harms are central.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103459"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147745140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between immature platelet count and clinical characteristics in pediatric immune thrombocytopenia","authors":"Emily M. Harris ,&nbsp;Michele P. Lambert ,&nbsp;Amanda Grimes ,&nbsp;Jenny Despotovic ,&nbsp;Jennifer A. Rothman ,&nbsp;Caitlyn McComb ,&nbsp;Brian Guedes ,&nbsp;Susan Kirk ,&nbsp;Abinaya Arulselvan ,&nbsp;Matthew Basara ,&nbsp;Brenna Cannon ,&nbsp;Sam King ,&nbsp;Andrew L. Frelinger ,&nbsp;Nan Chen ,&nbsp;Wendy B. London ,&nbsp;Rachael F. Grace","doi":"10.1016/j.rpth.2026.103417","DOIUrl":"10.1016/j.rpth.2026.103417","url":null,"abstract":"<div><h3>Background</h3><div>Despite the increasing number of treatments for immune thrombocytopenia (ITP), there are no established laboratory predictors of treatment response. Immature platelet fraction (IPF) and immature platelet count (IPC) are clinical laboratory measurements reflecting bone marrow thrombopoietic activity. The association between IPF and IPC and response to treatments, including thrombopoietin receptor agonists, has not been previously studied in children.</div></div><div><h3>Objectives</h3><div>This study evaluated the relationship among IPF, IPC, and treatment response in children with ITP.</div></div><div><h3>Methods</h3><div>This observational cohort study included 4 pediatric medical centers. Inclusion criteria were a diagnosis of ITP, ITP medication treatment, and an available clinical IPF measurement. Laboratory and clinical data were collected via medical record review.</div></div><div><h3>Results</h3><div>A total of 195 patients were included, with a median age at diagnosis of 7.5 years (range, 0.1-20.7). IPF was inversely associated with platelet count, whereas IPC was positively associated with platelet count. IPC at diagnosis and pretreatment was higher in overall responders than in nonresponders (<em>P</em> = .03 and <em>P</em> = .001, respectively). There were higher pretreatment platelet counts in overall responders than in nonresponders (<em>P</em> &lt; .001), but no differences in IPF at diagnosis or pretreatment between the treatment groups. Pretreatment IPC and platelet count were higher in corticosteroid responders than in nonresponders (<em>P</em> = .046 and <em>P</em> = .005, respectively), and in intravenous immunoglobulin responders than in nonresponders (<em>P</em> = .04 and <em>P</em> = .003, respectively). However, pretreatment IPF, IPC, and platelet counts did not differ between thrombopoietin receptor agonist responders and nonresponders.</div></div><div><h3>Conclusion</h3><div>Higher pretreatment platelet count and IPC correlate with overall treatment response, but the association varies by individual treatment. Biomarkers of treatment response are needed to inform individualized management.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103417"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147712366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential presence of neutrophil extracellular traps in serum vs plasma of patients with critical limb-threatening ischemia","authors":"Nicolas Gendron ,&nbsp;Anne Roche ,&nbsp;Vanessa Granger ,&nbsp;Joseph Emmerich ,&nbsp;Olivier Sanchez ,&nbsp;Pascale Gaussem ,&nbsp;David M. Smadja ,&nbsp;Luc de Chaisemartin","doi":"10.1016/j.rpth.2026.103441","DOIUrl":"10.1016/j.rpth.2026.103441","url":null,"abstract":"<div><h3>Background</h3><div>Neutrophil extracellular traps (NETs) contribute to both arterial and venous thrombosis. However, their detection in peripheral blood remains challenging, with circulating DNA and nucleosomes often used as surrogate markers.</div></div><div><h3>Objectives</h3><div>This study evaluated circulating NETs, nucleosomes, and double-stranded DNA (dsDNA) in different blood matrices, serum vs plasma, for the quantification of NET markers.</div></div><div><h3>Methods</h3><div>Thirteen patients with end-stage critical limb-threatening ischemia (CLTI) and 7 controls were included in this retrospective study. NETs (myeloperoxidase [MPO]–DNA complexes), nucleosomes, and dsDNA were quantified in serum and plasma samples from patients with CLTI, and in serum and various plasma types (EDTA, citrate, and heparin) in controls.</div></div><div><h3>Results</h3><div>MPO–DNA complexes were undetectable in plasma but significantly elevated in the serum of patients with CLTI compared with controls (median optical density, 0.048 vs 0.004; <em>P</em> = .012). Serum levels of nucleosomes and dsDNA were also significantly higher in patients with CLTI than in controls (<em>P</em> = .029 and <em>P</em> = .019, respectively) and higher in serum than in plasma (<em>P</em> &lt; .01). In controls, dsDNA and nucleosomes were also higher in serum than in plasma, but MPO–DNA complexes remained undetectable. Correlations among MPO–DNA, nucleosomes, and dsDNA were observed only in serum.</div></div><div><h3>Conclusion</h3><div>NETs, as evidenced by MPO–DNA complexes, were detectable only in the serum of patients with CLTI, supporting a disease-related origin. Our findings suggest that NET markers are more readily detectable in serum. However, the potential influence of coagulation-related processes during serum preparation should be considered. Our results highlighted the need for methodological standardization in NET biomarker measurements in clinical studies.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103441"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147712381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous vs interrupted direct oral anticoagulants for minimal bleeding-risk surgical procedures—a systematic review and meta-analysis","authors":"Alexander Xiang ,&nbsp;Shakil Popatia ,&nbsp;Sarah Lopes Sadafi ,&nbsp;Megha Rao ,&nbsp;Asim Shaikh ,&nbsp;Mehrad Nowrouzi ,&nbsp;Allen Li ,&nbsp;Ali Eshaghpour ,&nbsp;Mark Crowther","doi":"10.1016/j.rpth.2026.103419","DOIUrl":"10.1016/j.rpth.2026.103419","url":null,"abstract":"<div><h3>Background</h3><div>Evidence supporting the perioperative interruption of direct oral anticoagulants (DOACs) is varied, especially for procedures with minimal bleeding risk.</div></div><div><h3>Objectives</h3><div>This review compared the risk of bleeding events and thromboembolism in patients undergoing minimal bleeding-risk procedures, in whom DOACs were interrupted or continued.</div></div><div><h3>Methods</h3><div>Prospective, retrospective, and randomized trials examining a continuous or interrupted DOAC strategy in patients undergoing minimal bleeding-risk surgeries were included. Primary outcomes included the rates of venous or arterial thromboembolism and rates of major and minor bleeding events. Secondary outcomes included rates of surgical complications, mortality, and hospital length of stay.</div></div><div><h3>Results</h3><div>We retrieved 24 studies (<em>N</em> = 8663 patients). Cardiac ablations were the most common procedure (<em>n</em> = 13), followed by pacemaker insertion (<em>n</em> = 4) and dental procedures (<em>n</em> = 4). Nineteen studies examined thromboembolic events, with a pooled odds ratio (OR) favoring continuous DOAC use (OR, 0.54; 95% CI, 0.33-0.91; <em>I</em>² = 60%), although these results failed to persist in the high-quality randomized clinical trial data. Twenty studies examined bleeding events, with a significant reduction in major bleeds favoring continuous DOACs (OR, 0.57; 95% CI, 0.37-0.87; <em>I</em>² = 0%), which failed to reach significance in the randomized data. There were no difference in minor bleeding (OR, 0.93; 95% CI, 0.69-1.24; <em>I</em>² = 0%) events. No differences were noted in the rates of total complications or mortality.</div></div><div><h3>Conclusions</h3><div>While our meta-analysis found an improvement in thrombotic and major bleeding events with continuous perioperative DOAC use, these results were likely subject to selection bias with no significant differences in all outcomes in the high-quality randomized trials. The findings in the randomized data noted no significant differences between a continuous and interrupted DOAC strategy, although further research is required to provide a more definitive conclusion.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 3","pages":"Article 103419"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147712450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}