Journal of Thrombosis and Thrombolysis最新文献

{"title":"Antithrombotic strategies and outcomes in acute myocardial infarction-related cardiogenic shock requiring short-term mechanical circulatory support.","authors":"Rita Almeida Carvalho, João Presume, Ana Rita Bello, Christopher Strong, Jorge Ferreira, Catarina Brízido","doi":"10.1007/s11239-026-03413-1","DOIUrl":"https://doi.org/10.1007/s11239-026-03413-1","url":null,"abstract":"<p><strong>Background: </strong>Cardiogenic shock following acute myocardial infarction (AMI-CS) is associated with high mortality. Short-term mechanical circulatory support (ST-MCS) is frequently used after percutaneous coronary intervention (PCI) to stabilize hemodynamics. However, balancing anticoagulation (AC) and antiplatelet therapy in this setting poses substantial bleeding risk.</p><p><strong>Objectives: </strong>This study aimed to evaluate real-world antithrombotic strategies and associated ischemic and hemorrhagic complications in AMI-CS patients receiving ST-MCS.</p><p><strong>Methods: </strong>This retrospective, single-center study included all consecutive AMI-CS patients who underwent PCI and required ST-MCS between January 2017 and October 2024. AC and antiplatelet regimens were recorded from ST-MCS initiation until shock resolution. Ischemic and hemorrhagic events during this period were analyzed. The primary composite clinical endpoint was major adverse cardiovascular events (MACE), defined as a composite of ischemic events and all-cause mortality occurring during the period of cardiogenic shock.</p><p><strong>Results: </strong>Among 71 patients with AMI-CS who underwent PCI and required ST-MCS (mean age 62 ± 13 years, 69% male), in-hospital mortality was 56%, and MACE occurred in 42%. At ST-MCS initiation, 79% received triple therapy, decreasing to 39% by Day 7. Ischemic events were infrequent (8%) and mainly cerebrovascular. No cases of recurrent myocardial infarction or stent thrombosis were observed. Major bleeding (BARC ≥ 3) occurred in 32% of patients, typically within the first 48 h, and was more frequent in those supported with VA-ECMO.</p><p><strong>Conclusion: </strong>In AMI-CS patients requiring ST-MCS, ischemic events were uncommon, whereas major bleeding was frequent and occurred early. These findings underscore the need for individualized antithrombotic strategies in this high-risk population.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195031","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":"Thrombotic and hemorrhagic complications in NPM1-mutated AML: Association with APL-like immunophenotype and impact on early mortality.","authors":"Emine Merve Savaş, Lale Aydın Kaynar, Selin Küçükyurt, Hacer Berna Afacan Öztürk, Şahika Zeynep Akı, Murat Albayrak, Merih Kızıl Çakar, Aytek Peker, Haktan Bağış Erdem, Canan Topçuoğlu, Jale Yıldız, Asena Dikyar, Uğur Kalan, Ahmet Kürşad Güneş","doi":"10.1007/s11239-026-03410-4","DOIUrl":"https://doi.org/10.1007/s11239-026-03410-4","url":null,"abstract":"<p><p>NPM1-mutated acute myeloid leukemia (AML) is generally classified as favorable risk; however, early mortality remains a concern. A subset of NPM1-mutated AML exhibits a CD34-low/negative and HLA-DR-low/negative immunophenotype resembling acute promyelocytic leukemia (APL), raising the possibility that these patients may also share an increased susceptibility to coagulation abnormalities. While thrombotic and hemorrhagic complications are well recognized in APL, their frequency and prognostic significance in NPM1-mutated AML remain incompletely defined. In this single-center retrospective study, adult patients with newly diagnosed NPM1-mutated AML were included. Immunophenotyping was performed using multiparametric flow cytometry, and an APL-like immunophenotype was defined by low or absent CD34 and HLA-DR expression. Clinically significant thrombotic and hemorrhagic complications were recorded within the first 100 days, and early mortality (30-, 60-, and 100-day) was assessed as the primary survival outcome. A total of 70 patients were included, of whom 24 (34.3%) had an APL-like immunophenotype. Compared with the non-APL-like group, the APL-like group had lower fibrinogen levels (309.5 [211-421] vs. 410 [214-518] mg/dL; p = 0.015) and higher D-dimer levels (5.73 [2.4-9.2] vs. 2.50 [0.9-5.0] mg/L; p = 0.012) at diagnosis. Clinically significant thrombotic or hemorrhagic complications occurred in 12 patients (17.1%) and were more frequent in the APL-like group than in the non-APL-like group (33.3% vs. 8.7%; p = 0.017). In multivariable analysis, the APL-like immunophenotype (OR, 8.79; 95% CI, 1.46-53.05; P=0.018) and a white blood cell count > 35 × 10⁹/L (OR, 10.96 [1.48-80.92] p = 0.019) were independently associated with these complications. Compared with patients without complications, those with thrombotic or hemorrhagic complications had lower 30-day (66.7% vs. 93.0%; P = 0.006), 60-day (57.1% vs. 91.2%; p = 0.002), and 100-day OS (45.7% vs. 87.6%; p < 0.001). Thrombotic or hemorrhagic complications remained independently associated with 100-day mortality in multivariable Cox analysis (HR, 5.79 [1.85-18.06] p = 0.003). In NPM1-mutated AML, the immunophenotypically defined APL-like subset is associated with a procoagulant profile and an increased risk of clinically significant thrombotic and hemorrhagic complications; importantly, these events were independently associated with early mortality.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195026","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":"Severity-associated endothelial dysfunction in post-COVID-19 patients: flow-mediated dilation and vasoactive biomarkers.","authors":"Svitlana M Palii, Boryslav Selskyy, Svyatoslav Kostiv, Anastasia Voitovych, Kateryna Kozak, Oksana Shevchuk, Mykhaylo Korda, Sandor G Vari","doi":"10.1007/s11239-026-03404-2","DOIUrl":"https://doi.org/10.1007/s11239-026-03404-2","url":null,"abstract":"<p><p>COVID-19 is frequently associated with endothelial dysfunction, characterized by an imbalance between vasodilatory and vasoconstrictive mediators. This study evaluated endothelial function in the early post-COVID-19 period across groups of acute disease severity using flow-mediated dilation (FMD), circulating vasoactive biomarkers, and echocardiography. Serum endothelin-1 (ET-1), arginase-1 (Arg1), thromboxane A₂ (TxA₂)-related immunoreactivity, and prostacyclin (PGI₂)-related immunoreactivity were measured by enzyme-linked immunosorbent assay. An impaired FMD response was defined as < 10% brachial artery dilation from baseline. Overall, 502 post-COVID-19 patients were classified by acute COVID-19 severity as mild (n = 262), moderate (n = 183), severe (n = 41), or critical (n = 16); 27 healthy individuals served as a reference group. Impaired FMD responses were more frequent after severe (90.24%) and critical (100.00%) disease than in the reference group (18.52%). Greater acute disease severity was associated with progressively lower FMD values, smaller absolute brachial artery diameter changes, higher ET-1, Arg1, and TxA₂-related immunoreactivity, and lower PGI₂-related immunoreactivity. After adjustment for age, sex, body mass index, systolic blood pressure, smoking, diabetes mellitus, pre-existing cardiovascular disease, and post-COVID-19 interval, acute disease severity remained associated with impaired FMD (adjusted odds ratio 3.32, 95% confidence interval 2.29-4.82; p < 0.001 per one-category increase). Biomarker-FMD correlations were generally weak. Among patients assessed during the early post-COVID-19 period, greater acute COVID-19 severity was associated with greater impairment of endothelium-dependent vasodilation and an altered profile of circulating vasoactive biomarkers. These findings indicate associated functional and biochemical vascular abnormalities without establishing causality or a mechanistic relationship. Prospective longitudinal studies are needed to clarify their temporal evolution and clinical significance.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169742","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":"Structural and functional disruption of fibrinogen by a novel FGG c.1099G > C (p.Ala367Pro) variant: an integrated in silico mechanistic study.","authors":"Wenbin Tuo, Ye Zeng, Wu Wang, Jun Wang, QinZhen Cai, Mo Wu, Yun Xiang, Jun Guo","doi":"10.1007/s11239-026-03402-4","DOIUrl":"https://doi.org/10.1007/s11239-026-03402-4","url":null,"abstract":"<p><p>This study aimed to elucidate the molecular pathogenesis of the novel FGG p.Ala367Pro variant, recently identified in a patient with congenital dysfibrinogenemia (CD), using an integrated in silico approach. A comprehensive computational pipeline was applied. Pathogenicity was evaluated using MutationTaster, PolyPhen-2, PROVEAN, and VarCards. Structural effects were modeled with AlphaFold3 and analyzed via PyMOL. Protein stability was assessed using Missense3D, DUET, MUpro, DynaMut2, and I-Mutant2.0. Evolutionary conservation was evaluated using ConSurf and Clustal X. The p.Ala367Pro variant was consistently predicted to be deleterious by all pathogenicity prediction tools. Structural modeling indicated that the alanine-to-proline substitution predicteda local alpha-helix and abolishes a key hydrogen bond, leading to significant destabilization of the γ-chain tertiary structure (consistently negative ΔΔG values across stability prediction tools). The Ala367 residue was found to be perfectly conserved across species. These findings support a potentially mechanistic that the FGG p.Ala367Pro mutation is a pathogenic variant that disrupts fibrinogen function by compromising γ-chain stability and structure. Our work establishes a in silico framework for the functional validation of novel fibrinogen variants, crucial for interpreting genetic findings and guiding clinical management in CD.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167837","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":"Hemostatic dysfunction and thrombotic risk in metabolic dysfunction-associated steatotic liver disease.","authors":"Jakub Pawliński, Dominika Wójtowicz, Karolina Dzień, Artur Brudek, Jakub Janczura","doi":"10.1007/s11239-026-03408-y","DOIUrl":"https://doi.org/10.1007/s11239-026-03408-y","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic disorder with clinically relevant vascular and thrombotic consequences. Beyond hepatic steatosis, inflammation, and fibrosis, MASLD is associated with disturbances in hemostatic regulation that may shift the overall balance toward thrombosis. The prothrombotic phenotype of MASLD arises from the interaction of metabolic dysfunction, chronic inflammation, endothelial injury, platelet hyperreactivity, increased procoagulant activity, reduced natural anticoagulant capacity, and impaired fibrinolysis. These abnormalities may be detectable at early disease stages and appear to evolve with progression to steatohepatitis, advanced fibrosis, and cirrhosis. Epidemiological and clinical studies associate MASLD with venous thromboembolism, portal vein thrombosis, myocardial infarction, and ischemic stroke, with population-based data indicating approximately 1.8-fold higher venous thromboembolism risk and 3.4-fold higher PVT risk. However, conventional coagulation tests do not adequately reflect the net hemostatic balance, while candidate biomarkers and global hemostatic assays remain insufficiently validated for routine risk stratification. Hemostatic dysfunction in MASLD, particularly hypercoagulability, impaired fibrinolysis, endothelial dysfunction, and platelet activation, represents a clinically relevant but still underrecognized component of the disease. Clinical management should integrate liver disease stage, cardiometabolic burden, conventional thrombotic risk factors, and bleeding or procedural risk. Routine antiplatelet or anticoagulant therapy cannot currently be recommended solely on the basis of MASLD-related laboratory abnormalities.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166381","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":"Admission serum mitochondrial DNA relative abundance is associated with angiographic no-reflow or slow-flow after primary percutaneous coronary intervention in STEMI.","authors":"Shipeng Tian, Lili Wang, Qian Jia, Dongxiao Wang, Yaqing Shi, Gaoying Li","doi":"10.1007/s11239-026-03407-z","DOIUrl":"https://doi.org/10.1007/s11239-026-03407-z","url":null,"abstract":"<p><p>This study aimed to evaluate the independent association of admission serum mitochondrial DNA (mtDNA) relative abundance with no‑reflow or slow‑flow (NR/SF) after primary percutaneous coronary intervention (PPCI) in patients with acute ST‑segment elevation myocardial infarction (STEMI), and to quantify its incremental predictive value along the clinical timeline. We prospectively enrolled 892 consecutive STEMI patients undergoing PPCI and measured pre‑procedural serum mtDNA relative abundance using quantitative real‑time polymerase chain reaction (qPCR). After overlap weighting adjustment for 17 baseline covariates, high mtDNA abundance was independently associated with an increased risk of NR/SF (OR = 2.461, 95% CI 1.535-3.948, P < 0.001), with an absolute risk difference of 11.73%, and the exposure-response relationship exhibited a significant non‑linear threshold pattern (non‑linear P = 0.006). This association remained significant for both the NR component (OR = 2.689, 95% CI 1.377-5.250, P = 0.004) and the SF component (OR = 1.940, 95% CI 1.044-3.604, P = 0.036), and high mtDNA levels were also associated with higher in‑hospital risks of cardiogenic shock, acute heart failure, and severe arrhythmias. In predictive modeling, adding mtDNA to the early admission baseline model significantly improved the area under the curve (AUC) from 0.616 to 0.680 (ΔAUC = 0.064, DeLong P = 0.001), with a net reclassification improvement index of 0.453 and an integrated discrimination improvement index of 0.035. However, once angiographic or periprocedural characteristics were introduced, the incremental predictive value no longer reached statistical significance (ΔAUC = 0.023, P = 0.056-0.068). In conclusion, elevated admission serum mtDNA relative abundance is independently associated with post‑PPCI angiographic NR/SF in STEMI patients, showing a threshold‑like exposure-response relationship; its incremental predictive value is confined to the pre‑angiographic phase, suggesting that it may serve as an auxiliary biomarker for pre‑procedural risk stratification rather than an independent predictive tool.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167623","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":"Peli1 promotes sepsis-induced inflammation and coagulopathy by maintaining lipg stability in macrophages.","authors":"Yiwen Ma, Yi Shen, Jianmin Gu, Lin Shen, Junwen Zhou, Chunbing Zhang, Shen Zhang","doi":"10.1007/s11239-026-03386-1","DOIUrl":"https://doi.org/10.1007/s11239-026-03386-1","url":null,"abstract":"<p><p>Sepsis is marked by dysregulated inflammation and coagulopathy, with macrophages playing a central role. However, the molecular mechanisms linking macrophage dysfunction to sepsis-associated coagulopathy remain unclear. This study investigated the role of the E3 ubiquitin ligase Peli1 in sepsis progression and its downstream mechanism. Public scRNA-seq data from sepsis patients were analyzed to identify Peli1-associated immune signatures. Peli1 expression was validated in monocytes from sepsis patients and in CLP-induced septic mice. Peli1-deficient iBMDMs and myeloid cell-specific Peli1-deficient mice were used to assess its functional role. Transcriptomic profiling (RNA-seq), RT-qPCR, Western blotting, cycloheximide (CHX) chase assays, and co-immunoprecipitation (Co-IP) assays were performed to investigate the downstream molecular mechanisms and post-translational modifications. Peli1 was highly enriched in monocytes from fatal sepsis cases and markedly upregulated in monocytes from septic patients and CLP-induced septic mice. Peli1 deficiency attenuated macrophage inflammatory activation, improved platelet aggregation abnormalities, and enhanced survival in septic mice. Mechanistically, Lipg was identified as a crucial downstream target of Peli1 from transcriptomic analysis. Western blot and RT-qPCR validation confirmed that Peli1 predominantly regulated Lipg protein abundance through a post-transcriptional or post-translational mechanism, particularly under LPS-stimulated conditions. Peli1 was detected in the Lipg-immunoprecipitated complex, suggesting an association between Peli1 and Lipg. Further biochemical mapping revealed that Peli1 facilitated polyubiquitination specifically at the critical KR2 residue of Lipg to maintain its stability and shield it from proteasomal degradation. Ectopic restoration of Lipg successfully reversed the anti-inflammatory phenotypes and blunted cytokine production caused by Peli1 deficiency. Peli1 promoted sepsis-induced hyper-inflammation and coagulopathy by post-translationally maintaining Lipg stability in macrophages via site-specific ubiquitination. Target disruption of the Peli1-Lipg axis represents a promising therapeutic avenue to attenuate detrimental inflammation and immunothrombotic responses during sepsis.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111558","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":"Pulmonary embolism response team consulting practices and in-hospital outcomes in intermediate-high and high-risk pulmonary embolism.","authors":"Logan D Cho, Daniel J Snyder, Robert S Zilinyi, Ramya C Mosarla, Fahad Gul, Mahesh Madhavan, Justin A Fried, Estefania Oliveros, Jennifer H Haythe, Cara Agerstrand, Koji Takeda, Ajay J Kirtane, Sonal Pruthi, Ari J Mintz, Sahil A Parikh, Sanjum S Sethi","doi":"10.1007/s11239-026-03405-1","DOIUrl":"https://doi.org/10.1007/s11239-026-03405-1","url":null,"abstract":"<p><p>The goal of this analysis is to evaluate factors associated with PERT consultation and to determine if PERT consultation was associated with differences in outcomes for patients with intermediate-high and high-risk PE. All intermediate-high or high-risk PE cases at a single institution from 2016 to 2019 were reviewed. Outcomes were in-hospital mortality, length of stay (LOS), and moderate/severe bleeding. Clinical characteristics, imaging findings, and outcomes were compared between cases with and without PERT consultation. 335 cases were included, with PERT consulted in 52%. PERT was consulted more in cases with increased right ventricle (RV) size and depressed RV function (both p < 0.0001). PERT was consulted more for saddle (85.5%, p < 0.0001) and less for segmental (39.0%, p < 0.0001) PE. Use of catheter-based therapies, such as catheter-directed thrombolysis (23.0% vs. 1.9%, p < 0.001), was higher within the PERT group. Cases with PERT involvement had a shorter mean LOS (13 vs. 24 days), lower in-hospital mortality (8.1% vs. 21.0%), and less bleeding (9.8% vs. 21%) (all p < 0.004); there was no difference in PE-related mortality (p = 0.51). In multivariate analyses, PERT consultation was a predictor of lower in-hospital mortality (OR 0.30, CI 0.15-0.64, p = 0.002), bleeding (OR 0.43, CI 0.22-0.85, p = 0.01), and LOS (OR 0.38, CI 0.22-0.67, p = 0.0007). PERT was consulted more in cases of central PE and cases with greater signs of RV strain. PERT was associated with increased use of catheter-based therapies, lower in-hospital mortality and bleeding, and a shorter LOS.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111584","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":"Copeptin in acute ischemic stroke: a surrogate marker of AVP-system activation with temporal dynamics and clinical implications.","authors":"Ming Lei, Yanzhao Huang, Han Xu, Yi Deng, Langui Tang, Chunlian Zhao","doi":"10.1007/s11239-026-03313-4","DOIUrl":"10.1007/s11239-026-03313-4","url":null,"abstract":"<p><p>Copeptin, an inert peptide derived from provasopressin and co-released with arginine vasopressin (AVP), has emerged as a stable circulating indicator of AVP system activation and has attracted growing interest in acute ischemic stroke (AIS). Over the past decade, both experimental and clinical investigations have explored its potential clinical relevance. A central challenge, however, is to distinguish the biological role of AVP signaling from the interpretive significance of copeptin as a biomarker. Current evidence indicates that AVP signaling may contribute to key pathological processes, including cerebral edema formation and post-ischemic inflammatory responses. In contrast, copeptin appears to reflect activation of the neuroendocrine stress axis rather than acting as a direct effector within these pathways. Clinically, copeptin levels rise rapidly during the early phase of AIS and are consistently associated with stroke severity and adverse outcomes, supporting its potential utility in early risk stratification and prognostic assessment. The use of copeptin in combination with neuroimaging parameters and other biomarkers has been explored, with some studies suggesting improved performance in early clinical evaluation. However, whether copeptin confers meaningful incremental value beyond established tools remains uncertain. Interpretation of the available evidence is further limited by heterogeneity in study design, variability in sampling strategies, the lack of standardized cutoff values, and the scarcity of large-scale prospective validation. Taken together, copeptin may serve as a useful component within multimarker frameworks for AIS. Its clinical interpretation, however, should remain anchored to its role as a surrogate indicator of AVP pathway activation, rather than being extended to a direct mediator of ischemic injury.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1877-1885"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964018","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":"Two decades of pulmonary vascular disease and ischemic heart disease mortality in the united states: A longitudinal analysis using CDC WONDER (1999-2020).","authors":"Areesha Nawaz, Fnu Hafeezullah, Zainab Ali Siddiqui, Muhammad Shaheer Bin Faheem, Nazeer Ahmed, Razeena Zahid, Ali Zubair, Bushra Ghullam Muhammad, Jawad Ibrahim, Muhammad Raafay Jamil, Muhammad Khalid Afridi","doi":"10.1007/s11239-026-03329-w","DOIUrl":"10.1007/s11239-026-03329-w","url":null,"abstract":"<p><p>Pulmonary vascular disease (PVD) and ischemic heart disease (IHD) are major contributors to cardiovascular mortality in U.S. adults. This retrospective study aims to examine mortality trends and demographic disparities between 1999 and 2020. However, both diseases have been studied individually, but their combined temporal trends remain unexplored. The CDC WONDER database was used to obtain data for adults aged ≥ 45 years. AAMRs per 100,000 population and APC were calculated using Joinpoint regression, stratified by demographic, geographic, and urbanization categories. PVD and IHD together reported a total of 184,780 deaths. The overall AAMR increased from 6.9 to 8.9 per 100,000 between 1999 and 2020. Mortality rates were higher in men (8.8) compared to females (6.0) throughout the study period. Black or African American individuals had the highest AAMR (8.9), demonstrating a current surge in 2018. Similarly, non-metropolitan areas consistently experienced greater AAMR (8.5) than metropolitan areas (6.9), with a steep rise after 2018 (APC = 14.72%). Furthermore, mortality was greatest in the South; however, the Midwest region reported the highest AAMRs (8). Additionally, individuals aged 85 + had the highest CMR (44.6). Lastly, Vermont had the highest AMMRs (13.6) among other states. PVD- and IHD-related mortality depicted a recent steep increase despite an initial decline, with considerable differences across demographic and regional groups. This highlights the importance of a direct call to action by expanding preventive care, spreading awareness, and early diagnosis with management to address these inequities and decrease the growing burden.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"1972-1984"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005692","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}