Araci M R Rondon, Sophie Featherby, Tainá Gomes, El Houari Laghmani, Camille Ettelaie, Henri H Versteeg
{"title":"Comparison of the procoagulant activity between extracellular vesicles obtained from cellular monolayers and spheroids.","authors":"Araci M R Rondon, Sophie Featherby, Tainá Gomes, El Houari Laghmani, Camille Ettelaie, Henri H Versteeg","doi":"10.1007/s11239-025-03076-4","DOIUrl":"https://doi.org/10.1007/s11239-025-03076-4","url":null,"abstract":"<p><p>Tissue factor (TF) is the main activator of blood coagulation and is associated with thrombosis and tumor progression. It can be released into the blood circulation incorporated within cancer cell-derived extracellular vesicles (EVs). In this study, we investigated the influence of two-dimensional (monolayer) and three-dimensional (spheroid) tumor cell culture methods, and co-culture with cancer-associated fibroblasts (CAF), on the level of EVs release and the associated TF release and activity. The density of EVs and TF released from spheroids and monolayers of Hs578t human breast cancer and CAF were measured by the concentration of the phosphatidylserine and TF-ELISA. For some experiments, cells were activated using a protease-activated receptor (PAR)-2-activating peptide (PAR2-AP). The concentration and EV's size were accessed by nanoparticle tracking analysis, and a clotting assay was used to evaluate TF pro-coagulant activity. Hs578t monolayers released sevenfold more EVs, and it was associated with an 11-fold higher TF antigen release than the spheroids cultures. Activation of the cells with a PAR2-AP resulted in a significant increase in the release of EVs and TF from the Hs578t monolayers, but no significant increase was observed in the spheroids, only from half Hs578t, half CAF spheroids. Taken together, our results demonstrate that monolayer cell cultures are capable of releasing more significant amounts of EVs and associated TF than spheroid cultures. Monolayers and spheroids have different behavior when we compare the release of EVs and TF. It is essential to consider it when choosing a cell model to study cancer-associated thrombosis.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556904","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}
Paige Hanke, Ma Emmanuelle Domingo, Ghenella Salanio, Kulsoom Ahmed, Jingyu Hu, Kristin Hendricks, Jacob Howard, Tori Hashimura, Chris Guiliano, Bradley J Haan, Tsz Hin Ng, Denise Kelley, Tamara Knight, Kathleen Koopman, Monika Obstoj, Thomas Breeden, Dumitru Sirbu, Meredith Romano, Andrew Harpenau, Rebecca Konneker, Jason Acevedo, Neil Pan, Stephanie B Edwin
{"title":"Apixaban versus warfarin for treatment of venous thromboembolism in patients with severe renal impairment: a multicenter study.","authors":"Paige Hanke, Ma Emmanuelle Domingo, Ghenella Salanio, Kulsoom Ahmed, Jingyu Hu, Kristin Hendricks, Jacob Howard, Tori Hashimura, Chris Guiliano, Bradley J Haan, Tsz Hin Ng, Denise Kelley, Tamara Knight, Kathleen Koopman, Monika Obstoj, Thomas Breeden, Dumitru Sirbu, Meredith Romano, Andrew Harpenau, Rebecca Konneker, Jason Acevedo, Neil Pan, Stephanie B Edwin","doi":"10.1007/s11239-025-03075-5","DOIUrl":"https://doi.org/10.1007/s11239-025-03075-5","url":null,"abstract":"<p><p>Limited evidence exists regarding the use of factor Xa inhibitors for the treatment of venous thromboembolism (VTE) in patients with severe renal impairment. Notably, these patients were excluded from clinical trials.The goal of this study was to examine the safety and effectiveness of apixaban versus warfarin for the treatment of acute VTE in patients with severe renal impairment.This retrospective cohort study was conducted across 36 Ascension Health sites between 2014 and 2024. Adult patients receiving apixaban or warfarin for VTE treatment with severe renal impairment were included. The primary outcome was time to composite bleeding event within six months.This study included 1200 patients receiving apixaban and 600 patients receiving warfarin. Overall, 23.4% of the study population had ESRD requiring renal replacement therapy. Among patients not requiring renal replacement therapy, stage IV CKD was most common (43.8%). No difference in time to composite bleeding events (HR 1.01; 95% CI 0.74-1.38, p = 0.97) or recurrent VTE (HR 1.24; 95% CI 0.70-2.18, p = 0.46) were noted after controlling for confounders. Furthermore, major bleeding (4.7% vs. 7.5%, p = 0.43) and clinically-relevant non-major bleeding (4.3% vs. 6.2%, p = 0.08) were similar between groups. Apixaban was associated with a significantly reduced incidence of anticoagulation-related ED admission (6.8% vs. 9.8%, p = 0.02) compared to warfarin. Anticoagulation-related readmission (7.4% vs. 8%, p = 0.66) and time to all-cause mortality (5.2% vs. 6.2%, p = 0.38) were similar between groups.No differences in safety or effectiveness were noted between apixaban and warfarin, providing encouraging evidence to support the use of apixaban for treatment of acute VTE in patients with severe renal impairment.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476801","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}
Minqi Zhou, Difei Lu, Anna Jiang, Chenxu Zhao, Yao Lu, Bo Zheng, Linzi Miao, Youyuan Huang, Chenxue Qu, Ying Gao
{"title":"Hydrogen sulphide alleviates platelet dysfunction in patients with type 2 diabetes.","authors":"Minqi Zhou, Difei Lu, Anna Jiang, Chenxu Zhao, Yao Lu, Bo Zheng, Linzi Miao, Youyuan Huang, Chenxue Qu, Ying Gao","doi":"10.1007/s11239-025-03071-9","DOIUrl":"https://doi.org/10.1007/s11239-025-03071-9","url":null,"abstract":"<p><p>Hyperglycaemia stimulate platelet activation by reducing platelet H<sub>2</sub>S concentrations, potentially leading to cardiovascular events. Exogenous supplementation with H<sub>2</sub>S reversed this abnormal platelet activation under hyperglycaemia.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370801","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}
Mehmet Baysal, Elif Aksoy, Kübra Hilal Bedir, Deniz Özmen, Püsem Patır, Ufuk Demirci, Samet Yaman, Zehra Narlı Özdemir, Vildan Gürsoy, Esra Yıldızhan, Serkan Güven, Rafiye Çiftçiler, Yıldız İpek, İbrahim Ethem Pınar, Emine Eylem Genç, Sinan Mersin, Mehmet Can Uğur, Zeynep Tuğba Karabulut, Fehmi Hindilerden, İpek Yönal Hindilerden, Emine Gulturk, Melda Cömert, Volkan Karakuş, Nergiz Erkut, Abdülkerim Yıldız, Elif G Ümit, Ahmet Muzaffer Demir, Reyhan Diz Küçükkaya, Ahmet Emre Eşkazan
{"title":"Real-world data on direct oral anticoagulants in BCR::ABL1-negative myeloproliferative neoplasms (MPNs): a multicenter retrospective study on behalf of scientific subcommittee on MPNs for Turkish society of hematology.","authors":"Mehmet Baysal, Elif Aksoy, Kübra Hilal Bedir, Deniz Özmen, Püsem Patır, Ufuk Demirci, Samet Yaman, Zehra Narlı Özdemir, Vildan Gürsoy, Esra Yıldızhan, Serkan Güven, Rafiye Çiftçiler, Yıldız İpek, İbrahim Ethem Pınar, Emine Eylem Genç, Sinan Mersin, Mehmet Can Uğur, Zeynep Tuğba Karabulut, Fehmi Hindilerden, İpek Yönal Hindilerden, Emine Gulturk, Melda Cömert, Volkan Karakuş, Nergiz Erkut, Abdülkerim Yıldız, Elif G Ümit, Ahmet Muzaffer Demir, Reyhan Diz Küçükkaya, Ahmet Emre Eşkazan","doi":"10.1007/s11239-024-03043-5","DOIUrl":"10.1007/s11239-024-03043-5","url":null,"abstract":"<p><p>BCR::ABL1-negative myeloproliferative neoplasms (MPNs) pose a substantial risk of thrombosis, leading to significant morbidity and mortality. Anticoagulant therapy, historically based on vitamin K antagonists (VKAs), has limitations in preventing recurrent thrombotic events and managing bleeding complications. Direct oral anticoagulants (DOACs) offer a potential alternative with improved pharmacokinetics and compliance. However, evidence on DOAC efficacy and safety in MPNs remains limited, necessitating further investigation. In this multicenter retrospective study in Türkiye, we assessed real-world usage patterns and outcomes of DOACs in MPN patients. Data from 220 patients with PV, ET, or PMF receiving DOACs or VKAs for thrombosis or nonvalvular atrial fibrillation (NVAF) were collected from medical records. Thrombotic events and bleeding episodes were documented based on ISTH criteria. DOACs were used in 126 patients as first-line anticoagulant therapy or following VKAs. Ninety-four patients were on VKAs, of which 83 as a first-line treatment. There were eight thromboses (6.3%) seen in 126 DOAC patients, and similarly, seven episodes (9.4%) of thrombosis were observed in 94 patients using VKA. Major bleeding occurred in seven patients (5.6%) on DOAC and 3 (3.2%) in VKA. Thrombotic and bleeding risks were comparable between DOACs and VKAs (p = 0.708 and p = 0.158, respectively). The incidence rate of thrombosis in the VKA group is 1.1% and in the DOAC group is 1.9%. The incidence of major bleeding in the VKA group is 0.6% and 1.6% in the DOAC group. To the best of our knowledge, our study included the largest number of MPN patients to date, comparing DOACs with VKA in terms of both efficacy and safety, which suggests DOACs as promising alternatives to VKAs for managing thrombotic risk in MPNs with manageable toxicity. Despite the limitations of retrospective studies, DOACs' benefits in terms of efficacy and compliance warrant further investigation through prospective trials. Individualized treatment decisions should consider patient-specific factors, emphasizing collaborative efforts between specialists to optimize DOAC therapy in patients with MPNs. Comparable efficacy and safety between DOACs and VKAs were observed in MPN patients.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"284-298"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622266","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":"ASTRAL scale for predicting prognosis following intravenous thrombolysis with anterior versus posterior circulation acute ischemic stroke.","authors":"Yani Fan, Guoyan Shi, Yue Lv, Xianghui Kong, Yadan Lu, Lili Chen","doi":"10.1007/s11239-024-03049-z","DOIUrl":"10.1007/s11239-024-03049-z","url":null,"abstract":"<p><p>In this study, we compared whether there was any difference between the ASTRAL(Acute Stroke Registry and Analysis of Lausanne, ASTRAL) scale in predicting prognosis after IVT(Intravenous Thrombolysis, IVT) in patients with AIS(Acute Ischemic Stroke, AIS) in the ACI(Anterior Circulation Infarction, ACI) and PCI(Posterior Circulation Infarction, PCI), with the aim of providing more guiding information. Statistical analysis was performed using SPSS 25.0. When comparing the baseline characteristics, the normal distribution test was carried out first, which did not conform to the normal distribution. The continuous variables were expressed in the median and interquartile, and the nonparametric double-independent sample test was carried out. MedCalc software was used to plot ROC(Receiver Operating Characteristic, ROC) curves, calculate AUC(Area Under the Receiver Operating Characteristic Curve, AUC), and compare the prediction performance of the ASTRAL score by Delong text, and the difference of P < 0.05 was statistically significant. The AUCs of ASTRAL in predicting poor prognosis of ACI and PCI patients after IVT were 0.768 and 0.773, respectively. There was no difference in the AUC of ASTRAL score between ACI and PCI(P > 0.05). The ASTRAL scale has consistent prognostic predictive value for AIS in the anterior and posterior circulatory systems and is a reliable tool for predicting poor prognosis of patients with ACI and PCI after IVT.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"254-259"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377987","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}
Ian J Welsby, Darrell R Schroeder, Kamrouz Ghadimi, Gregory A Nuttall, Mark M Smith
{"title":"Thrombin generation after prothrombin complex concentrate or plasma transfusion during cardiac surgery.","authors":"Ian J Welsby, Darrell R Schroeder, Kamrouz Ghadimi, Gregory A Nuttall, Mark M Smith","doi":"10.1007/s11239-024-03061-3","DOIUrl":"10.1007/s11239-024-03061-3","url":null,"abstract":"<p><p>Thrombin generation (TG) is reduced after cardiac surgery using cardiopulmonary bypass (CPB), contributing to coagulopathy and bleeding. Plasma transfusion or four-factor prothrombin complex concentrate (PCC) are commonly used to treat coagulopathic bleeding after CPB without knowledge of how each may restore TG. To determine the effect of PCC infusion on restoration of thrombin generation compared with plasma transfusion, we performed a laboratory-based secondary analysis of a randomized, controlled trial of adult patients undergoing cardiac surgery to assess efficacy and safety of 4 F-PCC versus plasma for treatment of perioperative coagulopathic bleeding after CPB. Participants were randomized to receive either PCC (15 IU/kg) or plasma (10-15 ml/kg) after separation from CPB. Participant blood samples were obtained at pre-specified serial timepoints, with laboratory assays for TG and factor levels subsequently performed. The primary outcome was change in thrombin generation (TG) parameters after each randomized treatment through postoperative day 5. Secondary outcomes included serially derived clotting factor levels. Of 100 randomized participants, 99 were included in this laboratory analysis (PCC group, N = 51; plasma group, N = 48). After treatment, participants in the PCC group compared with those in the plasma group showed higher endogenous thrombin potential (ETP, Median, Interquartile range, IQR: 688 [371-1069] vs. 1088 [550-1691] nM minutes, P = 0.01), a greater increase din ETP (P = 0.002) and peak TG (P = 0.01) in the timepoints between heparin reversal and after treatment administration. Both groups demonstrated similar values in all TG assays by postoperative day 1 (P > 0.05). The PCC group also demonstrated higher levels of proteins C, S, and Factors II, VII, IX and X, early after treatment (P < 0.001 for all comparisons). Antithrombin levels were initially higher in the plasma group after treatment (Median, IQR: 66% [61-71%] vs. 56% [51-65%], P = 0.002) but differences did not persist beyond postoperative day 3. In this laboratory analysis from a recent randomized trial in adult cardiac surgery, PCC administration restored thrombin generation more rapidly than plasma in the early postoperative period without laboratory evidence of hypercoagulability. ClinicalTrials.gov identifier: NCT02557672 [1].</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"309-318"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780599","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":"Letter about 'Biochemical risk factors and outcomes of acute promyelocytic leukemia patients with thrombotic events: a matched pair analysis'.","authors":"Jingfei Zhou, Guomei Shi","doi":"10.1007/s11239-024-03053-3","DOIUrl":"10.1007/s11239-024-03053-3","url":null,"abstract":"","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"349-350"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564385","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}
Tanja Wenning, Claudia Kudlek, Ali Nuri Hünerlitürkoglu, Knut Kröger
{"title":"Risk of venous thromboembolism after discontinuing prophylactic or therapeutic anticoagulation in patients with haematologic malignancies because of thrombocytopenia.","authors":"Tanja Wenning, Claudia Kudlek, Ali Nuri Hünerlitürkoglu, Knut Kröger","doi":"10.1007/s11239-024-03047-1","DOIUrl":"10.1007/s11239-024-03047-1","url":null,"abstract":"<p><p>Although the rates of thrombocytopenia in patients with hematologic malignancies are well known, clinical reports of patients with haematological malignancies presenting with thrombocytopenia who developed venous thromboembolism (VTE) are rare. Defining the risk of VTE in patients with hematologic malignancies in whom anticoagulation is discontinued could help to individualize concepts of anticoagulation. We performed a retrospective analysis of medical records of patients with hematologic malignancies and thrombocytopenia grade 3 (25 × 10<sup>9</sup>/L to < 50 × 10<sup>9</sup>/L) or more severe in 2019-2022 in the Department of Haemato-Oncology at HELIOS Klinikum Krefeld. Data from 67 patients (34 (51%) males, 33 (49%) females) aged between 22 and 82 years (38 leukaemia, 23 lymphoma, 6 other) were included. Prophylactic anticoagulation was performed in 59 (88%) patients and therapeutic due to atrial fibrillation in 8 (12%). Anticoagulation was discontinued in 37 (55%) patients due to thrombocytopenia. Thrombotic events occurred in eight (12%) and minor bleeding in two (3%) patients. Seven patients developed a deep vein thrombosis (DVT) or superficial vein thrombosis (SVT) of the upper limbs, only one patient had a thrombosis of the femoral veins. Thrombotic event were much more frequent in patients suffering from leukaemia compared to lymphoma. Two thrombotic events occurred despite continued prophylaxis (2 of 30, 6.6%), the other six after discontinuing of anticoagulation (6 of 37, 16.2%). Both bleedings occurred in the group with continued anticoagulation. Five of the six patients with a thrombotic event, but without anticoagulation, received anticoagulation again despite a low platelet count and no bleeding was observed. Only one patient with jugular vein thrombosis and a platelet count around 4 × 10<sup>9</sup>/L remained without anticoagulation and no thrombus formation was observed. Risk of VTE in our patients with haematologic malignancies in whom anticoagulation is discontinued due to thrombocytopenia grade 3 is about 2.5 times higher than in patients in whom anticoagulation is continued and predominantly affects patients with leukaemia and upper extremity.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"260-266"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The protective effects of annexin A1 against oxidized-LDL-induced monocytes adhesion to endothelial cells: implication in atherosclerosis.","authors":"Xiaoling Zeng, Ruhui Qiu, Wen Peng","doi":"10.1007/s11239-024-03050-6","DOIUrl":"10.1007/s11239-024-03050-6","url":null,"abstract":"<p><p>Oxidized low-density lipoprotein (ox-LDL)-associated endothelial dysfunction is a critical factor in the initiation and progression of Atherosclerosis (AS). Annexin A1 is an important member of the annexin family. Despite its wide range of biological functions across various tissues and cells, the role of Annexin A1 in AS remains largely unexplored. In this study, we demonstrate that Annexin A1 treatment effectively reduced the expression of LOX-1 at both the mRNA and protein levels in HUVECs exposed to ox-LDL. Annexin A1 also ameliorated oxidative stress (OS) by decreasing mitochondrial ROS levels and restoring reduced GSH levels. Moreover, Annexin A1 decreased the expression of pro-inflammatory cytokines, including IL-6 and MCP-1. Importantly, Annexin A1 inhibited ox-LDL-induced expressions of the endothelial adhesion molecules, such as E-selectin and VCAM-1 in HUVECs, which leads to reduced attachment of THP-1 monocytes to HUVECs. Mechanically, we found that Annexin A1 reversed the expression of KLF2 against ox-LDL mediated by the PI3K/Akt axis. Notably, the silencing of KLF2 abrogated the protective effects of Annexin A1 on E-selectin and VCAM-1 expression and the attachment of THP-1 monocytes to HUVECs. Our findings suggest that Annexin A1 is a potential therapeutic agent for atherosclerosis, offering a novel approach to mitigate endothelial dysfunction and inflammation.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"267-275"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468838","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}
José D Oliveira, Gislaine Vieira-Damiani, Letícia Q da Silva, Guilherme R Leonardi, Camila O Vaz, Bruna C Jacintho-Robison, Bruna M Mazetto, Erich V de Paula, Fabíola Z Monica, Fernanda A Orsi
{"title":"Impact of antiplatelets, anticoagulants and cyclic nucleotide stimulators on neutrophil extracellular traps (NETs) and inflammatory markers during COVID-19.","authors":"José D Oliveira, Gislaine Vieira-Damiani, Letícia Q da Silva, Guilherme R Leonardi, Camila O Vaz, Bruna C Jacintho-Robison, Bruna M Mazetto, Erich V de Paula, Fabíola Z Monica, Fernanda A Orsi","doi":"10.1007/s11239-024-03057-z","DOIUrl":"10.1007/s11239-024-03057-z","url":null,"abstract":"<p><p>While the association between coronavirus disease-19 (COVID-19) and neutrophils extracellular traps (NETs) is recognized, uncertainties remain regarding its precise onset, timing of resolution and target therapy. To assess changes in inflammatory and NET markers during the first week of COVID-19 hospitalization, and the association with disease severity. \"In vitro\" experiments investigated the effect of antiplatelets, anticoagulants, and cyclic nucleotide stimulators on NETs release. Prospective cohort study, changes in interleukin (IL)-6, IL-8, IL-17, TNF-α, RANTES, PF4, and citrullinated-H3 (citH3) levels within each outcome group was evaluated using ANOVA. Differences between moderately ill, critically ill, and non-survivors were determined using Kruskal-Wallis and logistic regression. Healthy neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) or COVID-19 sera and treated with unfractionated heparin (UFH), low molecular weight heparin (LMWH), aspirin (ASA), ticagrelor, cinaciguat, sildenafil, and milrinone. The proportion of NETosis was assessed using IncuCyte Cell Imager. Of the 125 patients, 40.8% had moderate COVID-19, 40.8% had critical COVID-19 but recovered, and 18.4% died. From admission to hospitalization day 8, IL-6 levels decreased in moderately and critically ill, but not in non-survivors, while citH3 levels increased in critically ill and non-survivors. IL-6, IL-8, and TNF-α levels were associated with critical and fatal COVID-19. The release of NETs by neutrophils stimulated with PMA or COVID-19 sera was decreased in the presence of ASA, UFH, LMWH and cyclic nucleotide stimulators in a dose-dependent manner. In the first week of hospitalization, NET markers rose later than inflammatory markers in severe COVID-19 cases. Cyclic nucleotide stimulators, ASA and heparin may emerge as treatment approaches as they may modulate NETosis.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"199-209"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639221","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}