Journal of Thrombosis and Thrombolysis最新文献

{"title":"Ticagrelor 60 mg vs. 90 mg in elderly ACS patients with vs. without diabetes undergoing percutaneous coronary intervention.","authors":"Angelo Laino, Raffaele Piccolo, Mario Enrico Canonico, Marisa Avvedimento, Fiorenzo Simonetti, Roberta Paolillo, Fabrizio Dal Piaz, Bruno Charlier, Alessandra Spinelli, Stefano Cristiano, Luigi Di Serafino, Plinio Cirillo, Giuseppe Gargiulo, Anna Franzone, Amelia Filippelli, Valeria Conti, Giovanni Esposito","doi":"10.1007/s11239-026-03385-2","DOIUrl":"https://doi.org/10.1007/s11239-026-03385-2","url":null,"abstract":"<p><p>No data are available on the pharmacodynamic and pharmacokinetic profile of a low dose of ticagrelor as alternative to its standard dose during the early phase after acute coronary syndrome (ACS) according to diabetic status. We reported a post-hoc analysis of a randomized, crossover trial (NCT04739384) comparing ticagrelor 60 vs. 90 mg in elderly patients with ACS according to the presence or absence of diabetes. The primary endpoint was the pre-dose P2Y₁₂ reaction units (PRU) using the VerifyNow-P2Y₁₂ (Accumetrics, San Diego, CA, USA) at 14 days after treatment with ticagrelor 60 or 90 mg twice daily. Out of 50 patients, 24 (48%) had diabetes. Pre-dose PRU was similar between patients with diabetes (Least-squares means, LSM, difference_{60 vs. 90} -8.80, 95% confidence interval, CI, -26.7 to 9.15; p = 0.33) and those without diabetes (LSM difference_{60 vs. 90} 0.01, 95%CI -16.8 to 16.8; p = 0.99), without significant heterogeneity (p for interaction = 0.48). Consistently, transmittance aggregometry and multiple electrode aggregometry showed a similar pharmacodynamic profile between the two doses of ticagrelor in patients with and without diabetes. Plasma levels of ticagrelor were significantly lower using the 60 mg dose in both patients with diabetes (pre-dose: LSM difference_{60 vs. 90} -174 ng/mL, 95%CI -370 to 20.3; p = 0.08; post-dose: LSM difference_{60 vs. 90} -549 ng/mL, 95%CI -781 to -316; p < 0.001) and without diabetes (pre-dose: LSM difference_{60 vs. 90} -177 ng/mL, 95%CI -350 to -3.53; p = 0.05; post-dose: LSM difference_{60 vs. 90} -407 ng/mL; 95%CI -613 to -200; p < 0.001). Ticagrelor 60 mg twice daily provided a similar magnitude of platelet inhibition compared with ticagrelor 90 mg twice daily among elderly patients with ACS irrespective of diabetic status.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850967","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":"Plasminogen supplementation enhances alteplase fibrinolysis efficacy in a systemic embolization rat model.","authors":"Ahmet Davut Aksu, Eliška Brhelová, Jana Hložková, Jana Doležalová, Radka Opatřilová, Robert Mikulík, Peter Scheer","doi":"10.1007/s11239-026-03384-3","DOIUrl":"https://doi.org/10.1007/s11239-026-03384-3","url":null,"abstract":"<p><p>Enhancing the fibrinolysis efficacy of recombinant tissue plasminogen activators (r-tPA) may be achieved by increasing the blood plasminogen levels. This study evaluated the effect of plasminogen (PLG) addition to a clinically relevant alteplase (r-tPA) dose on fibrinolysis. Sixty nine Wistar albino rats were divided into 7 groups; control (n = 10), r-tPA 0.9 mg/kg (0.9r-tPA) (n = 10), r-tPA 0.9 mg/kg + PLG 8 IU/kg (0.9r-tPA+8PLG) (n = 10), r-tPA 0.9 mg/kg + PLG 16 IU/kg (0.9r-tPA+16PLG) (n = 10), r-tPA 0.6 mg/kg + PLG 8 IU/kg (0.6r-tPA+8PLG) (n = 10), r-tPA 0.6 mg/kg + PLG 16 IU/kg (0.6r-tPA+16PLG) (n = 10), and r-tPA 0.9 mg/kg + PLG 8 IU/kg (0.9r-tPA+8PLG60) (n = 9) with the PLG administered 60 min before the r-tPA administration. In all groups, systemic embolism was induced by application of three barium sulfate-labeled artificial clots in abdominal aorta. Artificial clots were visualized under micro-fluoroscopy, and radiographs were captured every 5 min during fibrinolytic/saline infusion. The measurement of clot area was used to calculate fibrinolysis rate (%/min) and the area under the curve (AUC; %*min). Results show that all PLG combinations enhanced fibrinolysis relative to untreated controls (p < 0.001). At the clinical 0.9 mg/kg dose, PLG supplementation significantly increased the fibrinolysis rate compared with r-tPA alone (r-tPA: 0.8 ± 0.5%/min; 8 IU/kg, p = 0.025; 16 IU/kg, p < 0.001), and this benefit was retained when PLG was administered 60 min in advance (p = 0.024). Differences between PLG doses were not statistically significant. Systemic plasminogen supplementation therefore enhances r-tPA-mediated fibrinolysis in vivo at a clinically relevant dose and regimen, without requiring catheter-directed delivery.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794903","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":"Efficacy and safety of low-dose tirofiban plus dual antiplatelet therapy in acute cerebral infarction beyond the thrombolysis window: a non-randomized trial with preliminary findings.","authors":"Jing Wang, Dexiang Liu, Birong Chen, Hongxia Zhao","doi":"10.1007/s11239-026-03388-z","DOIUrl":"https://doi.org/10.1007/s11239-026-03388-z","url":null,"abstract":"<p><p>Optimal antithrombotic strategies for patients with acute cerebral infarction beyond the thrombolysis window (6-24 h) without large or medium-sized vessel occlusion remain uncertain. This study evaluated the efficacy and safety of low-dose tirofiban combined with dual antiplatelet therapy (DAPT) in this population. This single-center, retrospective, non-randomized study enrolled 229 patients. The tirofiban group (n = 114) received low-dose tirofiban (0.1 µg/kg/min for 24 h) followed by DAPT, while the control group (n = 115) received DAPT alone. Inverse probability of treatment weighting (IPTW) balanced baseline covariates. The primary outcome was favorable functional outcome (modified Rankin Scale score 0-2) at 90 days. Secondary outcomes included excellent functional outcome (mRS 0-1 at 90 days), NIHSS improvement (≥ 3 points from baseline to 72 h) and early neurological deterioration (END). Safety outcomes included bleeding and symptomatic intracranial hemorrhage (sICH). Sensitivity analyses and E-values were calculated. After IPTW, all baseline covariates achieved excellent balance (all SMDs < 0.1). The primary outcome showed no significant difference between groups (OR = 0.41, 95% CI: 0.12-1.38, P = 0.151). However, tirofiban was associated with significantly higher odds of excellent functional outcome (mRS 0-1) (OR = 2.01, 95% CI: 1.07-3.77, P = 0.031) and NIHSS improvement (OR = 2.57, 95% CI: 1.42-4.66, P = 0.002). No significant differences were observed in END, bleeding, or sICH. Sensitivity analyses confirmed the robustness of tirofiban's benefit for both outcomes, with E-values of 4.58 and 3.43, respectively. Low-dose tirofiban combined with DAPT significantly improved early neurological recovery and excellent functional outcome without increasing bleeding or sICH risk. Although the primary outcome did not reach statistical significance, consistent sensitivity analyses support the clinical value of tirofiban. Larger randomized controlled trials are warranted.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794880","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":"Revisiting clinical scoring tools for the diagnosis of thrombotic thrombocytopenic purpura (TTP).","authors":"Shruti Kharat, Shrimati Shetty, Maushmi S Kumar","doi":"10.1007/s11239-026-03390-5","DOIUrl":"https://doi.org/10.1007/s11239-026-03390-5","url":null,"abstract":"<p><p>Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening hematologic emergency that leads to increased complexities and mortality due to diagnostic delays. Therapeutic plasma exchange (TPE) along with immunosuppressants is life-saving in cases with severe ADAMTS13 deficiency. Routine ADAMTS13 activity testing is unavailable in many diagnostic centers. Clinical heterogeneity also complicates the early differentiation of TTP from TTP-like syndromes. To critically examine the efficacy of contemporary clinical scoring systems used in the prediction of severe ADAMTS13 deficiency and guide early TPE initiation in the absence of ADAMTS13 activity testing. A literature search was made in PubMed, Embase, Scopus, and Cochrane Library databases from inception till December 2025. Only those studies evaluating PLASMIC, French, and Bentley scores in comparison with standard ADAMTS13 activity assays were included. Existing clinical scoring tools demonstrate high sensitivity in selected cohorts; their real-world utility is limited by modest specificity, population-dependent variability, and misclassification in complex clinical settings such as critical illness, pregnancy, malignancy, renal dysfunction, and old age. Clinical scoring systems facilitate early decision-making, but insufficient as stand-alone diagnostic tools. Overestimation of TTP risk may lead to unnecessary TPE exposure and increased healthcare cost. Emerging strategies, including rapid ADAMTS13 assays, biomarkers, and machine-learning approaches, may permit early TTP diagnosis and prompt management.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794865","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":"Venous thromboembolism prophylaxis in multiple myeloma patients receiving immunomodulatory therapy: a systematic review and meta-analysis.","authors":"Mark Tippins, Anna Loader, Bareq S Al-Lami, Sarah Al-Juboori, Abdulrahman O Saeed, Baqir S Al-Lami, Timothy Corbett","doi":"10.1007/s11239-026-03380-7","DOIUrl":"https://doi.org/10.1007/s11239-026-03380-7","url":null,"abstract":"<p><p>Patients with multiple myeloma receiving immunomodulatory drugs have an increased risk of venous thromboembolism (VTE), but the comparative effectiveness and safety of available prophylactic strategies remain uncertain. A systematic review and meta-analysis of randomized and prospective studies was conducted in accordance with PRISMA 2020. Studies evaluating aspirin, low-molecular-weight heparin (LMWH), warfarin, direct oral anticoagulants (DOACs), or no prophylaxis in patients receiving immunomodulatory therapy were included. Primary outcomes were symptomatic VTE and major bleeding. Twelve studies (n=2,435; 25 arm-level observations) were included. Descriptive pooled VTE incidence was 2.2% with apixaban, 5.1% with rivaroxaban, 5.6% with LMWH, 7.9% with aspirin, 9.1% with warfarin and 20.9% with no prophylaxis; these single-arm estimates are descriptive summaries of heterogeneous arms rather than adjusted between-class comparisons. LMWH significantly reduced VTE compared with warfarin, and aspirin reduced VTE compared with no prophylaxis. Major bleeding rates were low across active prophylaxis groups (0.3-1.6%). Evidence certainty was low or very low for every included study and very low for all DOAC evidence, reflecting small, heterogeneous and largely non-randomised studies. Active thromboprophylaxis is associated with substantially lower VTE incidence than no prophylaxis in patients with multiple myeloma receiving immunomodulatory therapy. Among established agents, LMWH has the most robust evidence base, though that base is itself of low certainty. Observations relating to DOACs, including apixaban, rest exclusively on very low certainty evidence from small prospective cohorts and feasibility studies and are strictly hypothesis-generating. Because the evidence is dominated by thalidomide-era regimens whereas contemporary therapy has evolved substantially, external validity to modern practice remains limited, and adequately powered randomised trials in current regimens are needed.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794862","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":"Prospective evaluation of systemic coagulation function during anti-amyloid monoclonal antibody therapy in Alzheimer's disease.","authors":"Bethany C Curd, Neal D Tolley, Miriam Santo, Jack Foster, Marina Leardini-Tristão, Shancy Jacob, Haley Benzon, Xiangyang Ye, Sachin J Shah, Mark A Supiano, Matthew T Rondina, Nicholas A Frost, Robert A Campbell, Anna L Parks","doi":"10.1007/s11239-026-03383-4","DOIUrl":"https://doi.org/10.1007/s11239-026-03383-4","url":null,"abstract":"<p><p>Anti-amyloid monoclonal antibodies such as lecanemab are increasingly used to treat Alzheimer's disease (AD) and are associated with amyloid-related imaging abnormalities (ARIA), including hemorrhagic findings (ARIA-H). Whether anti-amyloid therapy is associated with systemic alterations in coagulation function is unknown. We sought to evaluate systemic coagulation function in patients receiving lecanemab compared with untreated AD controls. We prospectively collected blood samples from 20 lecanemab-treated participants with AD at baseline and after 8-10 weeks of therapy, and from 48 untreated AD controls. We assessed thrombin generation in platelet-poor plasma initiated with tissue factor and measured lag time, time to peak, peak thrombin, velocity, and area under the curve. We also evaluated fibrin formation by turbidity assays, yielding maximum rate of clot formation and time to Vmax. Comparisons were performed between groups and within treated participants over time. Mean age was 72.8 years (SD 8.1); 51.5% were female. No significant differences were observed in thrombin generation or fibrin formation between treated and untreated participants, or from baseline to follow-up among treated participants. Two lecanemab-treated participants developed ARIA-H. Anti-amyloid monoclonal antibody therapy was not associated with detectable alterations in plasma coagulation parameters in this cohort. These findings do not support measurable systemic coagulation perturbations detectable in plasma but do not rule out localized cerebrovascular, endothelial, platelet-mediated, or other microvascular mechanisms underlying ARIA-H, which warrant future investigation.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional versus two-dimensional quantitative coronary angiography for coronary lesion assessment: a systematic review and meta-analysis.","authors":"Prakash Gupta, Roopeessh Vempati, Nader Alwifati, Joud Fahed, Mohammad Hamza, Asad Ur Rab, Ahmed Atef Mahmoud, Meet Patel, Ahmed Eisa, Marim Zoma, Prami Nakarmi, Muhammad Burhan, Mobeen Zaka Haider, Azka Naeem, Berke Cenktug Korucu, Haidar Hajeh, Shwetha Gopal, Ahmed Zulaid, Ishaq Khoury, Arhum Mahmood, Sai Pradsad Ramchandran, M Chadi Alraies","doi":"10.1007/s11239-026-03377-2","DOIUrl":"https://doi.org/10.1007/s11239-026-03377-2","url":null,"abstract":"<p><p>Accurate anatomical assessment of coronary lesions is fundamental to effective percutaneous coronary intervention (PCI). Conventional two-dimensional quantitative coronary angiography (2D-QCA) is limited by projection dependency, vessel overlap, and foreshortening, leading to imprecise estimation of lesion severity. Three-dimensional quantitative coronary angiography (3D-QCA), based on 3D reconstruction, provides more accurate vessel assessment than 2D analysis; however, its reported advantages remain inconsistent across studies. We conducted a systematic review and meta-analysis in accordance with PRISMA and Cochrane guidelines. PubMed, Embase, Scopus, and Cochrane Central were searched from inception to October 2025 for studies comparing 3D-QCA with 2D-QCA using validated software. Random-effects models pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs). Risk of bias was assessed using ROB-2 and the Newcastle-Ottawa Scale. Sixteen studies were included. Compared with 2D-QCA, 3D-QCA reported significantly longer lesion length (SMD 0.29; 95% CI 0.04-0.53) and larger minimal luminal area (SMD 0.36; 95% CI 0.07-0.65). Diameter stenosis (SMD - 0.28; 95% CI - 0.48 to - 0.07) and percent stenosis (SMD - 0.57; 95% CI - 0.95 to - 0.20) were lower with 3D-QCA. No significant differences were observed for bifurcation angle, minimal luminal diameter, reference vessel diameter, or reference vessel area. Moderate-to-high heterogeneity was observed across outcomes. 3D-QCA provides more precise anatomical characterization of coronary lesions than conventional 2D-QCA, particularly for lesion length and area-based metrics, supporting its role in improving PCI planning, while further outcome-driven studies are needed.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707058","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":"Muscle mass and quality by computed tomography predicts mortality and emergency department revisits in older adults with acute pulmonary embolism.","authors":"Victoria Hayman, Emilie Groulx-Boivin, Bojan Kovacina, Marc Afilalo, Jonathan Afilalo","doi":"10.1007/s11239-026-03357-6","DOIUrl":"https://doi.org/10.1007/s11239-026-03357-6","url":null,"abstract":"<p><p>Sarcopenia, the age-related loss of muscle mass and quality, is an indicator of frailty that can be objectively measured using computed tomography (CT) images acquired for other routine indications. CT-based muscle mass has been shown to predict adverse outcomes in many diseases, although evidence in acute pulmonary embolism (PE) is scant. A retrospective cohort study included patients ≥ 70 years diagnosed with acute PE between 2015 and 2019. Axial CT images at the carina and mid-thigh were used to measure chest muscle area (CMA), thigh muscle area (TMA), and thigh intramuscular fat area (TFMA) using semi-automated segmentation tools. Outcomes included 30-day mortality or unplanned emergency department (ED) revisit, hospital length of stay, disposition, and mortality at last follow-up. Logistic and Cox regression models were adjusted for the Pulmonary Embolism Severity Index (PESI). The cohort consisted of 205 patients (mean age 80 years; 63% females), with high-risk characteristics shown by a mean PESI score of 114. The incidence of 30-day mortality or ED revisit was 32%, 18%, and 12% in patients with low, intermediate, and high CMA, respectively (p = 0.01). CMA, TMA, and TFMA were independently and incrementally predictive of 30-day mortality or ED revisit, while CMA also predicted long-term mortality over 2 years. Patients with low muscle mass were more likely to have prolonged hospitalization and less likely to be discharged home. Muscle mass and quality can be opportunistically assessed from clinical CT scans and used to improve risk stratification and individualize decision-making in older adults with acute PE.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707052","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":"Apolipoprotein B100 and white matter hyperintensity as distinct mediators of thrombolytic response in acute stroke: preliminary findings.","authors":"Duanlu Hou, Yuanyuan Wang, Yuping Tang, Ping Zhong, Danhong Wu","doi":"10.1007/s11239-026-03370-9","DOIUrl":"https://doi.org/10.1007/s11239-026-03370-9","url":null,"abstract":"<p><p>Intracranial atherosclerotic stenosis (ICAS) and cerebral small vessel disease (CSVD) frequently co-exist and contribute to poor stroke outcomes. Whether distinct pathophysiological mechanisms mediate large-vessel versus small-vessel disease effects on stroke outcomes, and whether these are modifiable by thrombolysis, remains unknown. In this prospective cohort study, acute ischemic stroke patients with ICAS and/or CSVD were enrolled. ICAS was defined as ≥ 50% cerebral arterial stenosis and CSVD by white matter hyperintensity (WMH), microbleeds or lacunes. Baseline data, 2-week early neurological improvement (ENI), and 3-month modified Rankin scale (mRS) were recorded. Plasma lipids, apolipoprotein B100 (apoB100), homocysteine (HCY), etc., were measured. Logistic regression and causal mediation analyses tested independent predictors and mediators of ENI and poor 3-month outcome (mRS ≥ 3). 262 patients were included. Two novel mediating mechanisms were identified: First, thrombolysis improves early neurological recovery partly via apoB100 reduction (33% mediation, β = 0.33, 95% CI 0.01-0.87), revealing a previously unrecognized fibrinolysis-lipoprotein metabolic interaction. Second, small-vessel disease independently predicts poor 3-month outcomes (deep WMH: OR 2.35, p = 0.03) and additionally mediates 20% of HCY's effect (β = 0.20, 95% CI 0.03-0.46), establishing WMH as a dual-mechanism therapeutic target. Notably, apoB100 exhibits context-dependent mediation: it suppresses the true neurological damage of intracranial stenosis (53% mediation, β = 0.17, 95% CI 0.04-0.34) while facilitating thrombolytic benefit-demonstrating conditional biomarker action in acute stroke. We identified that apoB100 is a modifiable factor linking ICAS and thrombolysis to early neurological recovery, while WMH partly mediates the effect of hyperhomocysteinemia on 3-month functional outcomes. Monitoring and targeting apoB100 may improve secondary prevention strategies in the post-statin era for patients with combined large- and small-artery cerebrovascular disease.Trial registrationChiCTR1800018315, 11/09/2018.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697764","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":"Direct oral anticoagulant dose vs dual antiplatelet therapy after left atrial appendage closure in patients with nonvalvular atrial fibrillation: a systematic review and meta-analysis.","authors":"Umama Alam, Adam Umar Ahmed, Javeria Javed, Amna Khan, Muhammad Ansab, Iftikhar Khan, Shahzaib Rafi, Zonaira Mushahid, Bushra Nawaz, Muhammad Asad Asif, Rakhee Lohana, Shaiza Naseer Khan, Abdul Moiz, Fazeela Bibi, Bilal Aslam","doi":"10.1007/s11239-026-03381-6","DOIUrl":"https://doi.org/10.1007/s11239-026-03381-6","url":null,"abstract":"<p><p>Left atrial appendage closure (LAAC) is increasingly used in patients with non-valvular atrial fibrillation (NVAF) who are at high risk of bleeding. However, the optimal post-procedural antithrombotic strategy remains uncertain. This meta-analysis compares the efficacy and safety of direct oral anticoagulants (DOACs) versus dual antiplatelet therapy (DAPT) following LAAC. A systematic review and meta-analysis were conducted according to PRISMA and Cochrane guidelines. PubMed, Embase, and Cochrane were searched from inception to November 2025 for randomized controlled trials and cohort studies comparing DOACs with DAPT after LAAC in NVAF patients. Outcomes included all-cause mortality, cardiac mortality, stroke, major bleeding, device-related thrombosis (DRT), and thromboembolic events. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effects models as appropriate. Seven studies (3 RCTs and 4 observational studies) comprising 2,103 patients (1,003 DOAC; 1,096 DAPT) were included. DOAC therapy significantly reduced all-cause mortality (RR = 0.55, 95% CI 0.34-0.89), major bleeding (RR = 0.55, 95% CI 0.37-0.81), and device-related thrombosis (RR = 0.46, 95% CI 0.24-0.91) compared with DAPT. No statistically significant differences were observed for stroke, cardiac mortality, or overall thromboembolic events, although effect estimates consistently favored DOACs. Thromboembolic events associated with major bleeding were markedly lower with DOACs (RR = 0.14, 95% CI 0.05-0.36). However, sensitivity analyses restricted to randomized controlled trials did not demonstrate statistically significant benefits for all-cause mortality, major bleeding, or device-related thrombosis. Therefore, the observed overall benefit appeared to be mainly driven by observational studies, and these findings should be interpreted cautiously. DOAC therapy after LAAC may be associated with a favorable clinical profile compared with DAPT, with significant reductions in all-cause mortality, major bleeding, and device-related thrombosis in the overall pooled analysis. However, these benefits were not confirmed in sensitivity analyses restricted to randomized controlled trials and appeared to be primarily driven by observational studies. Therefore, these findings should be interpreted cautiously and should not be used to support a definitive preference for DOACs over DAPT without further adequately powered randomized evidence.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685157","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}