Journal of Thrombosis and Haemostasis最新文献

{"title":"Joint effects of atrial fibrillation and prothrombotic genotypes on the risk of ischemic stroke","authors":"Erin Mathiesen Hald ,&nbsp;Maja-Lisa Løchen ,&nbsp;Ellisiv B. Mathiesen ,&nbsp;Kristian Hveem ,&nbsp;Sigrid K. Brækkan ,&nbsp;John-Bjarne Hansen","doi":"10.1016/j.jtha.2024.12.022","DOIUrl":"10.1016/j.jtha.2024.12.022","url":null,"abstract":"<div><h3>Background</h3><div>Atrial fibrillation (AF) is a major risk factor for ischemic stroke. Whether prothrombotic single nucleotide polymorphisms (SNPs) impact stroke risk in AF is not well known.</div></div><div><h3>Objectives</h3><div>To investigate the joint effects of 5 prothrombotic SNPs and AF on ischemic stroke risk.</div></div><div><h3>Methods</h3><div>A subcohort (<em>n</em> = 14 583) was randomly sampled from the Tromsø (1994-2012) and the Trøndelag Health (1995-2008) studies. DNA was genotyped for rs8176719 (ABO blood type), rs6025 (factor [F]V Leiden), rs1799963 (prothrombin G20210A), rs2066865 (fibrinogen-γ), and rs2036914 (F11). Hazard ratios (HRs) with 95% CIs for incident ischemic stroke were estimated by AF status for individual SNPs and by categories of a genetic risk score.</div></div><div><h3>Results</h3><div>A total of 1091 participants developed AF during follow-up, of whom 169 (15.5%) subsequently had a stroke. Having ≥1 risk allele in prothrombin, FV Leiden, F11, or fibrinogen-γ was not associated with excess stroke risk in AF. In the absence of AF, ≥1 risk allele(s) in ABO was not associated with stroke (HR, 1.03; 95% CI, 0.85-1.25), whereas those with AF and ≥1 risk allele(s) in ABO had a 1.4-fold increased stroke risk compared with those with AF and no risk allele (HR, 1.42; 95% CI, 0.99-2.04). There was no linear increase in stroke risk across categories of the genetic risk score in participants either with or without AF.</div></div><div><h3>Conclusion</h3><div>Most prothrombotic SNPs were not associated with ischemic stroke risk, regardless of AF status. The ABO SNP was associated with ischemic stroke risk in those with AF only.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1401-1406"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progesterone regulates gut microbiota mediating bone marrow mesenchymal stem cell injury in immune thrombocytopenia patients during pregnancy","authors":"Qi Chen ,&nbsp;Fengqi Liu ,&nbsp;Gaochao Zhang ,&nbsp;Qingyuan Qu ,&nbsp;Yuxiu Chen ,&nbsp;Menglin Li ,&nbsp;Qiusha Huang ,&nbsp;Haixia Fu ,&nbsp;Xiaolu Zhu ,&nbsp;Yun He ,&nbsp;Xiaojun Huang ,&nbsp;Xiaohui Zhang","doi":"10.1016/j.jtha.2024.12.027","DOIUrl":"10.1016/j.jtha.2024.12.027","url":null,"abstract":"<div><h3>Background</h3><div>Immune thrombocytopenia during pregnancy (PITP) is the most common cause of platelet reduction in early and mid-pregnancy. However, the pathogenesis of PITP is still unclear.</div></div><div><h3>Objectives</h3><div>To determine the characteristics of bone marrow mesenchymal stem cells (BM-MSCs) in PITP patients and to explore the associations between metabolites, the gut microbiota, and BM-MSCs in PITP.</div></div><div><h3>Methods</h3><div>The characteristics of BM-MSCs were detected through <em>in vitro</em> and <em>in vivo</em> experiments. Nontargeted metabolomics was used to screen metabolites. The features of the gut microbiota were analyzed by 16S rDNA sequencing. PITP and fecal microbiota transplantation (FMT) mouse model were established to explore the associations between metabolites, gut microbiota, and BM-MSCs.</div></div><div><h3>Results</h3><div>BM-MSCs from PITP patients had significant senescence and apoptosis, as well as impaired immunoregulatory function. Metabolomic analysis indicated that progesterone was the most significant specific metabolite in PITP patients. <em>In vivo</em> studies showed that progesterone mediated MSC injury. Further analysis of the gut microbiota and FMT experiments revealed that progesterone mediated BM-MSCs injury by regulating the composition of the gut microbiota in PITP. RNA sequencing analysis of BM-MSCs from FMT mice revealed abnormal expression of genes related to cell aging and the NOD-like receptor signaling pathway.</div></div><div><h3>Conclusion</h3><div>In conclusion, BM-MSCs in the PITP were significantly impaired, which was associated with increased progesterone and changes in the gut microbiota regulated by progesterone. Intervening with the gut microbiota may become a new treatment for PITP.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1428-1441"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932190","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":"Exosite crosstalk in thrombin","authors":"James C. Fredenburgh ,&nbsp;Jeffrey I. Weitz","doi":"10.1016/j.jtha.2025.01.003","DOIUrl":"10.1016/j.jtha.2025.01.003","url":null,"abstract":"<div><div>Thrombin is the central mediator of hemostasis, where it converts fibrinogen to fibrin, activates upstream factors to promote coagulation, activates factor XIII and thrombin-activatable fibrinolysis inhibitor to stabilize fibrin, mediates anticoagulation, and modulates cellular activity via cell surface receptors. Thus, regulation of thrombin activity is essential to the hemostatic balance. Thrombin is regulated by positively charged surface domains that surround the active site. These exosites bind substrates, inhibitors, cofactors, and receptors, which coordinate to direct thrombin to the appropriate location and modulate catalytic activity. Thus, the exosites are essential to the activity and regulation of thrombin. In addition to acting as binding sites, the exosites modulate the active site allosterically. Furthermore, the exosites impact each other, whereby the binding of ligands to one exosite impacts the function of the opposing exosite. Given the integral role that exosites play in the regulation of thrombin, they are attractive targets for the regulation of thrombin and for the development of new anticoagulants.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1160-1168"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023948","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":"Prolonged vs standard thromboprophylaxis in patients with esophageal cancer undergoing surgery: a randomized controlled study","authors":"Tua Gyldenholm ,&nbsp;Nina Madsen ,&nbsp;Niels Katballe ,&nbsp;Daniel Willy Kjær ,&nbsp;Thomas Decker Christensen ,&nbsp;Anne-Mette Hvas","doi":"10.1016/j.jtha.2025.01.002","DOIUrl":"10.1016/j.jtha.2025.01.002","url":null,"abstract":"<div><h3>Background</h3><div>Recent guidelines recommend prolonged thromboprophylaxis after esophagectomy due to cancer. However, to our knowledge, no previous studies have examined if prolonged prophylaxis is superior to standard in-hospital prophylaxis.</div></div><div><h3>Objectives</h3><div>We aimed to perform the first clinical randomized study testing the efficacy of a prolonged 1-month thromboprophylaxis with low-molecular-weight heparin vs the standard treatment.</div></div><div><h3>Methods</h3><div>The study was an open-label, randomized, controlled trial including patients undergoing esophagectomy. The primary endpoint was the difference in prothrombin fragment 1 + 2 (F1 + 2) levels 1 month after surgery between the standard group and the intervention group. The secondary endpoints were the incidence of venous thromboembolic events and mortality.</div></div><div><h3>Results</h3><div>The study was terminated before reaching the expected sample size of 100 patients due to low accrual. We included 79 patients. At follow-up 1 month after surgery, F1 + 2 levels did not differ between the standard group and the intervention group (<em>P</em> = .41). Incidence of venous thrombosis was similar in the 2 groups, with 13% in the standard group and 15% in the intervention group. Preoperative F1 + 2 levels were significantly higher in patients who developed a venous thrombosis within 1 month after surgery than in those who did not (<em>P</em> = .01). The odds ratio of venous thromboembolism per 50 pmol/L increase in F1 + 2 was 1.64 (95% CI, 1.17-2.54). No patients died within 1 month after surgery.</div></div><div><h3>Conclusion</h3><div>No benefit of prolonged thromboprophylaxis after esophagectomy was found. Preoperative F1 + 2 levels were found to be a predictor for the incidence of postoperative thromboembolism.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1367-1378"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Estimation of gestational age-specific reference intervals for coagulation assays in a neonatal intensive care unit using real-world data”: comment from Karlaftis et al.","authors":"Vasiliki Karlaftis ,&nbsp;Chantal Attard ,&nbsp;Vera Ignjatovic ,&nbsp;Paul Monagle","doi":"10.1016/j.jtha.2024.12.019","DOIUrl":"10.1016/j.jtha.2024.12.019","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1452-1453"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768016","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":"Sex-specific DNA methylation marks associated with sex-biased risk of recurrence in unprovoked venous thromboembolism","authors":"Ohanna C.L. Bezerra ,&nbsp;Marc Rodger ,&nbsp;Gaëlle Munsch ,&nbsp;Michael J. Kovacs ,&nbsp;Grégoire Le Gal ,&nbsp;Pierre-Emmanuel Morange ,&nbsp;David-Alexandre Trégouët ,&nbsp;Celia M.T. Greenwood ,&nbsp;France Gagnon","doi":"10.1016/j.jtha.2025.01.004","DOIUrl":"10.1016/j.jtha.2025.01.004","url":null,"abstract":"<div><h3>Background</h3><div>Whether to stop oral anticoagulants after a first unprovoked venous thromboembolism (VTE) is challenging, partially due to an intriguingly higher risk of VTE recurrence (rVTE) in men after therapy discontinuation. DNA methylation (DNAm) differences between men and women might underlie this sex-biased rVTE risk difference.</div></div><div><h3>Objectives</h3><div>To investigate sex-specific associations between DNAm at cytosine-phosphate-guanine (CpG) sites and rVTE.</div></div><div><h3>Methods</h3><div>In 417 unprovoked VTE patients, including 101 experiencing recurrences over a 5-year follow-up (REcurrent VEnous thromboembolism Risk Stratification Evaluation [REVERSE] I), we analyzed blood DNAm using the Illumina EPIC array and performed a sex-stratified epigenome-wide association study. We further examined 181 major provoked VTE patients, including 36 recurrences over a 14-year follow-up (the MARseille THrombosis Association [MARTHA]), to investigate whether DNAm is a risk factor for rVTE after anticoagulation therapy.</div></div><div><h3>Results</h3><div>Hypomethylated CpGs at genes <em>TBC1D22B-</em>cg01060850 and <em>ZHX2-</em>cg07808424 in men and <em>DIP2B-</em>ch.12.1038646R and <em>DENND3-</em>cg03401656 in women were associated with rVTE at genome-wide level (<em>P</em> &lt; 7x10−8). Though not statistically significant, <em>DENND3-</em>cg03401656 had the same direction of effect in MARTHA women. Sensitivity analysis confirmed the robustness of the estimates, including potential confounders, adaptations of the Cox model, non-Europeans, and proximal methylation quantitative trait loci in the association. The associated CpGs were situated at genes for membrane trafficking, corroborating the participation of Rab regulatory proteins in rVTE and transcription factors.</div></div><div><h3>Conclusion</h3><div>We identified DNAm marks as potential risk factors for sex-biased recurrence in unprovoked VTE. Further replication and experimental validation could refine our understanding of the regulation of the identified DNAm sites and help optimize personalized decision-making for long-term anticoagulation after a first VTE.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1379-1392"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrin film on clots is increased by hematocrit but reduced by inflammation: implications for platelets and fibrinolysis","authors":"Ghadir Alkarithi ,&nbsp;Cédric Duval ,&nbsp;Helen R. McPherson ,&nbsp;Leander Stewart ,&nbsp;Ilaria De Simone ,&nbsp;Fraser L. Macrae ,&nbsp;Robert A.S. Ariëns","doi":"10.1016/j.jtha.2024.12.023","DOIUrl":"10.1016/j.jtha.2024.12.023","url":null,"abstract":"<div><h3>Background</h3><div>Blood clot formation, triggered by vascular injury, is crucial for hemostasis and thrombosis. Blood clots are composed mainly of fibrin fibers, platelets, and red blood cells (RBCs). Recent studies show that clot surfaces also develop a fibrin film, which provides protection against wound infection and retains components such as RBCs within the clot. However, the role of fibrin films in thrombi remains poorly understood.</div></div><div><h3>Objectives</h3><div>To explore the relationship between fibrin films and inflammation, RBC concentration, platelets, and fibrinolysis activity.</div></div><div><h3>Methods</h3><div>We used laser scanning confocal and scanning electron microscopy, enzyme-linked immunosorbent assay, and turbidity and fibrinolysis assays to investigate the interactions between fibrin film and inflamed endothelium, RBCs, platelets, and fibrinolysis.</div></div><div><h3>Results</h3><div>We found that plasma clots forming on top of inflamed endothelial cells show less fibrin film coverage and are characterized by higher fiber density and shorter lag time compared with control cells. Blood clots formed under conditions of high hematocrit showed significantly more fibrin film coverage than low hematocrit clots. We found that platelet adhesion was significantly reduced on clots with film compared with clots without film even when platelets were preactivated. Fibrinolysis was faster in clots without film than in clots with film, partly due to reductions in plasmin generation.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that reductions in fibrin film formation under thromboinflammatory conditions support continued clot growth through effects on increased platelet adhesion and activation. On the other hand, increased fibrin film impairs fibrinolysis. These data show a multifaceted role of the fibrin film in clot growth and stability.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1247-1259"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute pulmonary embolism with and without hemodynamic instability (2003-2022): a Swiss nationwide epidemiologic study","authors":"Simon Wolf ,&nbsp;Luca Valerio ,&nbsp;Riccardo M. Fumagalli ,&nbsp;Stavros V. Konstantinides ,&nbsp;Silvia Ulrich ,&nbsp;Frederikus A. Klok ,&nbsp;Suzanne C. Cannegieter ,&nbsp;Nils Kucher ,&nbsp;Stefano Barco","doi":"10.1016/j.jtha.2024.12.040","DOIUrl":"10.1016/j.jtha.2024.12.040","url":null,"abstract":"<div><h3>Background</h3><div>Data on the epidemiologic burden of acute pulmonary embolism (PE) in Switzerland are unavailable. Knowledge gaps remain on trends in PE-related comorbidities, PE severity, and length of in-hospital stay (LOS) at a nationwide level.</div></div><div><h3>Objectives</h3><div>To study the epidemiology of acute PE with a focus on overall trends, sex-stratified trends, and trends in patients with (vs without) hemodynamic instability.</div></div><div><h3>Methods</h3><div>We used nationwide, patient-level data including all patients aged 15 years or older hospitalized for PE in Switzerland from 2003 to 2022, amounting to <em>N</em> = 180 600. Additionally, we analyzed the Swiss Death Registry for the same period. We estimated the disease-specific age-standardized incidence rates, mortality rates, in-hospital case fatality rates, proportional mortality rates, and LOS. Analyses were stratified by sex and the presence of features of high-risk PE.</div></div><div><h3>Results</h3><div>During the study period, the PE-related incidence rate increased from 0.87 (95% CI: 0.82, 0.92) per 1000 population in 2003 to 1.19 (95% CI: 1.15, 1.24) in 2022. In contrast, a decreasing trend was found for mortality rates (18.7 [95% CI: 16.8, 20.6] per 100 000 population in 2003, 13 [95% CI: 11.7,14.2] in 2022), in-hospital case fatality rate (9.8 [95% CI: 9.1, 10.5] deaths per 100 hospitalized PE patients in 2003, 7.9 [95% CI: 7.4, 8.5] in 2019, subsequent increase during COVID-19 pandemic), and LOS (11 [Q1-Q3: 7-18] days in 2003, 8 [Q1-Q3: 4-16] in 2022). No major sex differences in trends were present. Except for LOS reduction, patients with high-risk features presented with similar trends.</div></div><div><h3>Conclusion</h3><div>The incidence of acute PE in Switzerland increased over the last 20 years. Despite increasing trends in the median age at PE diagnosis, in-hospital case fatality and mortality rates decreased, particularly among patients with high-risk features, and the LOS progressively declined.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1340-1351"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of ischemic stroke after cancer diagnosis: a population-based matched cohort study","authors":"Deborah M. Siegal ,&nbsp;Joshua O. Cerasuolo ,&nbsp;Marc Carrier ,&nbsp;Peter L. Gross ,&nbsp;Moira K. Kapral ,&nbsp;David Kirkwood ,&nbsp;Ronda Lun ,&nbsp;Michel Shamy ,&nbsp;Rinku Sutradhar","doi":"10.1016/j.jtha.2024.12.029","DOIUrl":"10.1016/j.jtha.2024.12.029","url":null,"abstract":"<div><h3>Background</h3><div>There are limited data regarding the association between cancer and ischemic stroke, particularly among individuals with previous stroke.</div></div><div><h3>Objective</h3><div>Our objective was to measure and compare the risk of ischemic stroke in individuals with and without cancer.</div></div><div><h3>Methods</h3><div>Population-based matched cohort study in Ontario, Canada. Participants aged ≥18 years with a new diagnosis of cancer were matched (1:1) to cancer-free controls by age and sex in 2 separate matched cohorts based on the absence (matched cohort 1) or presence (matched cohort 2) of prior ischemic stroke. The primary outcome was the incidence of ischemic stroke. We calculated subdistribution adjusted hazard ratios (aHR) and 95% CIs for ischemic stroke (death as a competing event).</div></div><div><h3>Results</h3><div>In matched cohort 1, the rate and risk of ischemic stroke were higher among 620,647 patients with cancer versus 620,647 controls at 1.5 years (4.6/1000 person-years [95% CI, 4.5-4.7] vs 3.5/1000 person-years [95% CI, 3.4-3.6]; aHR, 1.40; 95% CI, 1.34-1.47). In matched cohort 2, the rate and risk of ischemic stroke were similar among 13,924 patients with cancer and 13,924 controls at 1.5 years (26.9/1000 person-years [95%CI 25.1-28.9] vs 22.0 /1000 person-years [95% CI, 20.7-23.4]; aHR, 1.00; 95% CI, 0.88-1.14). In both cohorts, the risk of ischemic stroke was lower in patients with cancer versus controls from 1.5 to 5 years (aHR, 0.72; 95% CI, 0.69-0.74 and aHR, 0.53; 95% CI, 0.46-0.62).</div></div><div><h3>Conclusions</h3><div>Compared with cancer-free controls, the rate and risk of ischemic stroke were higher 1.5 years after cancer diagnosis in individuals without prior stroke and varied according to cancer site and stage.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1269-1277"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971489","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 tenecteplase bridging reperfusion ameliorates cerebral ischemia/reperfusion injury by improving microvascular circulation in rats","authors":"Yue-Xin Ning,&nbsp;Ji-Ru Cai,&nbsp;Ting-Ting Wang,&nbsp;Yi-Han Wang,&nbsp;Yu Cui,&nbsp;Hui-Sheng Chen","doi":"10.1016/j.jtha.2024.12.042","DOIUrl":"10.1016/j.jtha.2024.12.042","url":null,"abstract":"<div><h3>Background</h3><div>Endovascular thrombectomy (EVT) alone was not demonstrated to be noninferior to intravenous alteplase bridging EVT in acute large vessel occlusion stroke. Using the cerebral ischemia/reperfusion (I/R) injury model, intravenous tenecteplase (TNK) was administrated after ischemia, followed by reperfusion at various time points.</div></div><div><h3>Objectives</h3><div>To investigate whether intravenous TNK bridging EVT vs EVT alone could improve I/R injury, and this effect may be associated with the time from TNK to reperfusion.</div></div><div><h3>Methods</h3><div>Rats received intravenous TNK (1.4 mg/kg) or vehicle (sterile water) 1.0 hours after middle cerebral artery occlusion, followed by reperfusion after 0.5 or 1.0 hours following TNK. Neurological deficit scores, infarct volume, and brain edema were measured 24 hours after middle cerebral artery occlusion. Microthrombi were determined by immunofluorescence staining for CD31⁺/fibrinogen⁺ and CD31⁺/thrombocyte⁺. Inflammatory cell infiltration in the ischemic brain region was determined by flow cytometry.</div></div><div><h3>Results</h3><div>Compared with vehicle, TNK significantly reduced neurological deficit scores, brain infarction, neuroinflammation, and blood-brain barrier disruption, and significantly reduced intravascular fibrin and platelet deposition and brain inflammatory cell infiltration in the penumbra of I/R rats. Furthermore, a better beneficial trend was found in TNK bridging reperfusion at 0.5 hours after TNK compared with TNK bridging reperfusion at 1.0 hours after TNK.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that intravenous TNK bridging reperfusion produced neuroprotective action through dissolving microvascular thrombus and alleviating inflammatory cell infiltration to improve microcirculation, with the result of maintaining blood-brain barrier integrity and inhibiting neuroinflammation, and the neuroprotective benefit may be associated with the time from TNK to reperfusion.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1352-1366"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007528","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}