Thrombosis Journal最新文献

{"title":"Echogenicity of carotid plaques as a predictor of regression following lipid-lowering therapy.","authors":"Cheng-Hui Fan, Ying Hao, Lyu-Fan Chen, Jing Cheng, Yi-Qiong Wang, Ling-Hao Xu, Ji-Ming Li","doi":"10.1186/s12959-025-00753-5","DOIUrl":"10.1186/s12959-025-00753-5","url":null,"abstract":"<p><strong>Objective: </strong>Atherosclerotic plaque regression under lipid-lowering therapy shows considerable individual variation, and the factors influencing this variability remain incompletely understood. This study aimed to investigate the relationship between carotid plaque echogenicity and plaque regression in patients receiving lipid-lowering therapy, and to identify ultrasound characteristics that might predict plaque regression.</p><p><strong>Methods: </strong>A total of 838 patients with carotid plaques receiving lipid-lowering therapy were enrolled between July 2020 and May 2024 and followed up for 12 months. Carotid ultrasound was performed at baseline and follow-up to evaluate plaque characteristics. Plaque regression was defined as meeting any of the following criteria: (1) reduction in plaque area ≥ 5%, (2) decrease in plaque thickness ≥ 0.4 mm, or (3) reduction in plaque number, as assessed by vascular ultrasound imaging. Plaque echogenicity was classified into three types: hypoechoic, hyperechoic, and mixed echogenicity. Cox proportional hazards regression analysis was performed to assess the association between plaque echogenicity and plaque regression, adjusting for potential confounding factors.</p><p><strong>Results: </strong>Hypoechoic plaques showed higher rates of regression (72.8%) compared to hyperechoic (37.7%) and mixed echogenicity plaques (50.0%) (p < 0.001). After adjusting for confounding variables, hypoechoic plaques exhibited greater odds of regression compared to hyperechoic plaques (adjusted HR = 4.52, 95% CI: 3.18-6.43, p < 0.001). Additionally, the median percentage reduction in plaque size was more pronounced in hypoechoic plaques, (15.2%, IQR: 7.7-22.3%) compared with other echogenicities (p < 0.001).</p><p><strong>Conclusion: </strong>Carotid plaque echogenicity is strongly associated with the likelihood plaque regression, with hypoechoic plaques exhibiting higher regression rates and greater reductions in plaque size. These findings may help guide personalized treatment strategies and improve risk assessment.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"66"},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically predicted the causal association between serum mineral elements with immune thrombocytopenia and Henoch-Schonlein purpura: a bidirectional two-sample Mendelian randomization analysis.","authors":"Yan Chen, Xiuli Hong, Yamei Chen, Zhiqiang Xu, Quanyi Lu","doi":"10.1186/s12959-025-00756-2","DOIUrl":"10.1186/s12959-025-00756-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Worldwide, the diagnosis and treatment of immune thrombocytopenia (ITP) and Henoch-Schönlein purpura (HSP) remain a major and ongoing challenge in hematology. Emerging clinical evidences suggest serum mineral elements are associated with ITP or HSP, but the causal relationship between them is still unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;Conducting a two-sample, bidirectional Mendelian randomization (MR) study to evaluate the causal association between serum mineral elements including zinc, copper, magnesium, iron and calcium with ITP and HSP.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this two-sample, bidirectional MR study, summary statistics data of genome-wide association studies (GWAS) on exposures including zinc, copper, iron, magnesium and calcium were extracted from the MRC-Integrative Epidemiology Unit (MRC-IEU). The GWAS data on study outcomes, including ITP and HSP, were obtained from the FinnGen consortium. MR-Egger intercept and MR-PRESSO global test were utilized to assess the heterogeneity and horizontal pleiotropic of instrumental variables (IVs) between the exposures and outcomes, respectively. Inverse variance weighted (IVW) test was used as the primary analysis method to evaluate the causal between serum mineral elements with the risk of ITP and HSP, and weighted-median, weighted model, MR steiger, MR-PRESSO and radial MR were used as auxiliary analysis methods, moreover, the odds ratio (OR) and 95% confidence interval (CI) were calculated. Reverse MR analysis was also conducted. Leave-one-out test was further to conduct whether the association between serum mineral elements and the risk of ITP and HSP remain robust.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;No significant horizontal pleiotropy and heterogeneity between individuals IVs was found after MR-Egger and MR-PRESSO global test. Genetically predicted that high copper (OR = 0.768, 95%CI: 0.628-0.937) and magnesium (OR = 0.314, 95%CI: 0.112-0.884) concentrations may reduce the risk of ITP and HSP, respectively. High calcium concentration may increase the risk of HSP (OR = 1.823, 95%CI: 1.226-2.712). There was no significant evidence to support a causal association between iron, zinc, magnesium, and calcium with the risk of ITP, or between iron, copper, and zinc and the risk of HSP (all P &gt; 0.005). Moreover, no reverse causal associations between five serum mineral elements with the risk of ITP and HSP were found (all P &gt; 0.05), suggesting the causal associations between serum mineral elements with ITP and HSP were not bidirectional. In addition, consistent results were obtained by multiple sensitivity analyses, indicating the associations of serum mineral elements with the risk of ITP and HSP relatively robust.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In this MR study, we discovered genetically predicted that elevated serum levels of copper and magnesium decreased the risk of ITP and HSP, respectively, and elevated levels of serum calcium increased the risk of HSP. ","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"65"},"PeriodicalIF":2.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-leaflet reconstruction surgery for severe chronic lower limb venous insufficiency caused by post-thrombotic syndrome: a case report and literature review.","authors":"Dafang Liu, Hui Zhao, Jie Zhang, Liang Zhao, Yingfeng Wu","doi":"10.1186/s12959-025-00752-6","DOIUrl":"10.1186/s12959-025-00752-6","url":null,"abstract":"<p><strong>Background: </strong>A considerable number of patients with deep vein thrombosis of the lower extremities will develop post-thrombotic syndrome even after receiving standardized anticoagulation therapy. Damage to the femoral vein valves caused by post-thrombotic syndrome can lead to severe chronic lower limb venous insufficiency and currently there is a lack of effective treatment.</p><p><strong>Case presentation: </strong>We present a patient with pigmentation and itching due to post-thrombotic syndrome, where the anterior leaflet of the first set of valves in the superficial femoral vein was completely destroyed, while the posterior leaflet, although structurally intact, was adhered to the vessel wall. By reconstructing the posterior leaflet of the femoral vein valve and simultaneously narrowing the lumen where the anterior leaflet was located through suture ligation, we restored the valve's function to prevent venous reflux. During a 12-month follow-up period, the patient's quality of life significantly improved.</p><p><strong>Conclusions: </strong>Single-leaflet reconstruction surgery may serve as a potential treatment option for patients with post-thrombotic syndrome.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"64"},"PeriodicalIF":2.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A heterozygous nonsense mutation in the FGB gene (c.1299G > A) causes congenital fibrinogen disorder across four consecutive generations.","authors":"Wanling Chen, Jiasheng Hu","doi":"10.1186/s12959-025-00746-4","DOIUrl":"10.1186/s12959-025-00746-4","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to elucidate the molecular abnormalities in a four-generation Chinese family affected by congenital fibrinogen disorder (CFD).</p><p><strong>Case presentation: </strong>The proband was a 5-year-old Chinese boy with CFD. Routine clotting tests revealed decreased plasma fibrinogen concentration in the proband and in his father and sister. Notably, the condition presented was clinically asymptomatic. Whole exome sequencing identified a heterozygous c.1299G > A mutation in exon 8 of the FGB gene, leading to p.Trp433* (TGG > TGA). Further Sanger sequencing revealed the presence of this mutation in his great-grandmother, grandfather, father, and sister as well.</p><p><strong>Conclusion: </strong>The FGB gene variant c.1299G > A (p.Trp433*) across four consecutive generations is associated with CFD.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"63"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eno1 in sepsis-induced coagulopathy: a pleiotropic mechanism hypothesis involving immunomodulation and endothelial dysfunction.","authors":"Ke Qin, Xiao Chen, Xiaoling Li, Wenbin Zhang, Xinnan Song, Yuan Wang, Xiaowen Hu, Jianfeng Zhang","doi":"10.1186/s12959-025-00750-8","DOIUrl":"10.1186/s12959-025-00750-8","url":null,"abstract":"<p><strong>Background: </strong>Septic-induced coagulopathy (SIC) is a major cause of mortality in sepsis, closely associated with endothelial glycocalyx damage. Enolase 1 (Eno1), a key enzyme in glycolysis, plays a crucial role in sepsis-related systemic inflammation and the maintenance of glycocalyx integrity.</p><p><strong>Objective: </strong>This study utilizes multi-omics analysis to investigate the Eno1-regulated network, providing a comprehensive understanding of its molecular mechanisms in SIC.</p><p><strong>Methods: </strong>We used RNA-seq datasets to identify Eno1-related gene sets through weighted gene co-expression network analysis and validated their biological functions via gene set enrichment analysis.</p><p><strong>Results: </strong>Through RNA-seq analysis, we identified gene sets associated with Eno1 involved in immune regulation, endothelial cell apoptosis, coagulation, and glycosaminoglycan metabolism. Immune infiltration analysis revealed that Eno1 modulates SIC pathogenesis by influencing T cells and macrophages, with significant associations with endothelial dysfunction and inflammatory markers. Additionally, we observed that Eno1 regulation of glycolysis is linked to endothelial glycocalyx degradation, contributing to microcirculatory and vascular impairments in SIC. Furthermore, preliminary studies suggest that melatonin treatment may alleviate glycocalyx damage by inhibiting Eno1-mediated glycolytic pathways, offering a potential new therapeutic avenue for intervening in endothelial injury associated with SIC.</p><p><strong>Conclusions: </strong>This study underscores the critical role of Eno1 in promoting SIC and its potential as both a diagnostic marker and therapeutic target for glycocalyx repair. The multi-omics approach provides valuable insights into the molecular networks regulating SIC, offering new avenues for targeted interventions in sepsis management.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"62"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cystic adventitial disease of the popliteal artery in female: case report and literature review of a rare differential diagnose of artery stenosis.","authors":"Yuheng Wang, Chao Guo, Yi Huang, Xinyang Zhang, Feng Zhu, Dan Shang","doi":"10.1186/s12959-025-00734-8","DOIUrl":"10.1186/s12959-025-00734-8","url":null,"abstract":"<p><strong>Background: </strong>Cystic adventitial disease (CAD) is a rare vascular condition that causes arterial stenosis due to the presence of a cyst in the adventitia (outer layer) of the artery. It is most commonly seen in young and middle-aged men, with an occurrence rate of around 0.1% among vascular diseases. Symptoms may include intermittent claudication, rest pain, and, in severe cases, ulcers or limb ischemia. CAD is often underdiagnosed due to its rarity and the broad range of differential diagnoses for arterial obstruction.</p><p><strong>Case presentation: </strong>This case describes a 36-year-old female who presented with sudden left lower limb soreness that worsened with activity over five days, but without symptoms such as intermittent claudication or rest pain, which are typically associated with other vascular diseases. The patient had no significant history of smoking or other risk factors for peripheral arterial disease. Imaging studies, including angiography, revealed a focal filling defect and luminal narrowing in the popliteal artery (PA), which suggested the presence of an abnormality in the vessel wall. Given the findings and the patient's symptoms, surgical intervention was planned. The procedure involved the resection of the affected portion of the artery and replacement with an autologous vein graft. Pathological examination of the resected arterial segment confirmed the diagnosis of CAD, revealing a cyst in the adventitia filled with a gelatinous substance.</p><p><strong>Conclusion: </strong>CAD is a rare but important cause of arterial obstruction and the etiology of CAD is still unclear. It should be considered in younger patients with symptoms of limb ischemia, especially without smoking history or traditional risk factors. Imaging techniques, such as ultrasound and CT/MRI angiography, are crucial for diagnosis. Surgical management, typically involving resection and autologous grafting, is often required to alleviate symptoms and prevent further vascular complications. However, it is worth mentioning that conservative treatments, such as avoiding triggering movements, are sometimes sufficient. Since CAD is rarely suspected, awareness of this condition can help in making an early diagnosis, potentially avoiding misdiagnosis and improving patient outcomes.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"59"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interventional therapy for a case of Mycoplasma pneumoniae pneumonia complicated by upper extremity arterial embolism in a child: a case report.","authors":"Ziyuan Zhang, Yunchao Sun, Jianmin Wang, Xin Zhang, Na Guo, Shaolong Niu, Zening Ma","doi":"10.1186/s12959-025-00748-2","DOIUrl":"10.1186/s12959-025-00748-2","url":null,"abstract":"<p><strong>Background: </strong>Mycoplasma pneumoniae pneumonia complicated with arterial embolism in children is rare but progresses rapidly, potentially leading to severe limb ischemia and disability. This study reports a case of MPP complicated with upper limb arterial embolism and reviews relevant literature to explore its pathogenesis, treatment strategies, and clinical management principles.</p><p><strong>Case presentation: </strong>On January 9, 2025, Hebei Provincial Hospital of Traditional Chinese Medicine admitted an Asian male pediatric patient with upper limb arterial embolism. The patient developed acute limb ischemia secondary to Mycoplasma pneumoniae pneumonia and was diagnosed with upper limb arterial embolism. Endovascular thrombectomy was performed, followed by postoperative anticoagulation, anti-infective therapy, and traditional Chinese medicine treatment. After comprehensive management, the ischemic condition of the affected limb significantly improved, with no obvious functional impairment, achieving satisfactory therapeutic outcomes.</p><p><strong>Conclusion: </strong>The risk of thrombosis in children with Mycoplasma pneumoniae pneumonia is often overlooked by clinicians. Due to its rapid progression and potentially severe consequences, early identification of thrombotic risk is crucial. A multidisciplinary approach should be adopted to determine the most appropriate treatment strategy for each patient, aiming to improve prognosis and reduce the risk of disability.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"60"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time series differences in coagulopathy in mechanically ventilated COVID-19 and bacterial pneumonia patients: a nationwide observational study in Japan.","authors":"Ryo Hisamune, Kazuma Yamakawa, Noritaka Ushio, Katsunori Mochizuki, Tadashi Matsuoka, Yutaka Umemura, Mineji Hayakawa, Hirotaka Mori, Akira Endo, Takayuki Ogura, Atsushi Hirayama, Hideo Yasunaga, Takashi Tagami, Kohji Okamoto, Akira Takasu","doi":"10.1186/s12959-025-00747-3","DOIUrl":"10.1186/s12959-025-00747-3","url":null,"abstract":"<p><strong>Background: </strong>Severe acute respiratory syndrome coronavirus 2 infection causes systemic immune overresponse (cytokine storm), which can lead to microthrombi and dysfunction of coagulation such as disseminated intravascular coagulation (DIC) of sepsis. Coronavirus disease 2019 (COVID-19) coagulopathy is known to occur mainly in the pulmonary microcirculation. We aimed to investigate hematological differences in coagulopathy between COVID-19 pneumonia and bacterial pneumonia.</p><p><strong>Methods: </strong>We performed an observational cohort study using the Japanese REsearch of COVID-19 by assEmbling Real-world data (J-RECOVER) study database for COVID-19 patients and the Japan Medical Data Center (JMDC) database for bacterial pneumonia patients. The J-RECOVER database includes data from patients discharged between January 1 and September 31, 2020. The JMDC database covers patients emergently hospitalized from 2014 to 2022. We analyzed the association between hematological coagulopathy, systematic inflammation, and organ dysfunction in both groups after one-to-one propensity score matching.</p><p><strong>Results: </strong>We enrolled 572 COVID-19 patients and 2,413 bacterial pneumonia patients who required mechanical ventilation. The COVID-19 group was younger, had higher intensive care unit admission rates, and lower mortality in comparison to the bacterial group (p < 0.05). On day 1, the two groups showed no significant differences in JAAM-2 and sepsis-induced coagulopathy criteria. After matching, platelet counts, antithrombin activity, and prothrombin time-international normalized ratio were consistently maintained within normal ranges in the COVID-19 group. However, trends in D-dimer and fibrin degradation products in the COVID-19 group were similar to those in the bacterial pneumonia group.</p><p><strong>Conclusions: </strong>COVID-19 coagulopathy differs from bacterial septic DIC by exhibiting lower platelet consumption and minimal vascular hyperpermeability. Consequently, management strategies for COVID-19 coagulopathy should be distinct from those for septic DIC.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"61"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors for deep venous thrombosis following total hip arthroplasty: a meta-analysis.","authors":"Tao Wang, Qi Zhang, Zhiyong Hou","doi":"10.1186/s12959-025-00744-6","DOIUrl":"10.1186/s12959-025-00744-6","url":null,"abstract":"","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"58"},"PeriodicalIF":2.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Escalating doses of intravenous APAC demonstrate antithrombotic effect in pigs.","authors":"Zsuzsa Bagoly, Annukka Jouppila, Rita Orbán-Kálmándi, Linda Lóczi, Dóra Bomberák, Zsófia Anna Kádár, Ádám Deák, Ádám Mátrai, Ildikó Beke Debreceni, János Kappelmayer, Norbert Németh, Riitta Lassila","doi":"10.1186/s12959-025-00742-8","DOIUrl":"10.1186/s12959-025-00742-8","url":null,"abstract":"<p><strong>Background: </strong>Locally acting antiplatelet and anticoagulant (APAC) is developed as an antithrombotic agent for administration during vascular interventions and in thrombo-inflammatory conditions. APAC has entered human studies as a dual inhibitor of von Willebrand factor-mediated platelet recruitment on collagen and thrombin generation. We aimed to assess safety and escalating intravenous (i.v.) doses of APAC on hemostasis using a large animal model.</p><p><strong>Methods: </strong>We studied escalating APAC boluses (0.15-1.5 mg/kg; n = 11) and their reversal in anesthetized pigs for pharmacodynamics using functional coagulation testing. In some experiments, aspirin (500 mg) was co-administered with APAC, and protamine sulfate for reversal. Blood was repeatedly sampled for blood cell counts (CBC), activated partial thromboplastin time (APTT), prothrombin and thrombin time (PT, TT), thrombin generation (TG), activated clotting time (ACT), rotational thromboelastometry (ROTEM), and collagen-induced platelet aggregation (CIPA).</p><p><strong>Results: </strong>APAC was well-tolerated, and CBC remained stable. APAC modestly inhibited CIPA at high doses, while APTT, TT and ACT, unlike PT, prolonged dose-dependently. The anticoagulant ED₅₀ doses of APAC and UFH showed similar range (0.54 vs. 0.43 mg/kg), but UFH lasted longer and was less reversible by protamine. At 0.75 mg/kg of APAC, TG was abolished, InTEM coagulation and clot formation times were prolonged ≥ 2.8-fold, maximum clot firmness was reduced to 8-45%, and amplitude to 35-80%. APAC effects were transient (T_1/2 APAC = 30 min), and reversible by protamine.</p><p><strong>Conclusions: </strong>Escalating i.v. doses of APAC were safe and provided modest platelet inhibition.Our results indicate that the dose-dependent anticoagulation effects of APAC can be monitored using conventional laboratory assays.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":"23 1","pages":"57"},"PeriodicalIF":2.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}