Thrombosis research最新文献

{"title":"Thromboinflammation in ischemic cerebrovascular patients with the JAK2V617F mutation.","authors":"Marie Hvelplund Kristiansen, Morten Kranker Larsen, Laura Massarenti, Vibe Skov, Lasse Kjær, Christian Enevold, Sisse Rye Ostrowski, Claus Henrik Nielsen, Hans Carl Hasselbalch, Troels Wienecke","doi":"10.1016/j.thromres.2024.109236","DOIUrl":"10.1016/j.thromres.2024.109236","url":null,"abstract":"<p><strong>Background: </strong>The JAK2V617F mutation is a driver of Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) and is also implicated in cardiovascular diseases. Thrombosis in MPN involves JAK2V617F-associated platelet activation and endothelial dysfunction, all potentially influenced by chronic inflammation. Whether the mutation affects thromboinflammatory markers similarly in non-MPN patients remains unclear.</p><p><strong>Method: </strong>We conducted a study involving 63 ischemic cerebrovascular patients with the JAK2V617F mutation, matched with 63 patients without the mutation. Serum samples were analyzed for 12 thromboinflammatory markers during the acute phase and at three months follow-up.</p><p><strong>Results: </strong>Overall, there was no significant difference in thromboinflammatory markers between cases and controls. However, subgroup analysis of patients with a JAK2V617F allele burden ≥1 % (n = 15) showed higher levels of Vascular Cell Adhesion Molecule-1 (VCAM-1) at baseline (p = 0.018), and elevated Interleukin-10 (IL-10) (p = 0.004) and Tumor Necrosis Factor α (TNF-α) (p = 0.018) at follow-up compared to controls. Regression analysis revealed an association between higher JAK2V617F allele burden and increased VCAM-1 at baseline (p < 0.001), and higher VCAM-1 (p = 0.012), IL-10 (p = 0.003), and TNF-α (p = 0.034) at follow-up.</p><p><strong>Conclusion: </strong>In ischemic cerebrovascular patients, the JAK2V617F mutation is associated with elevated markers of endothelial dysfunction and chronic inflammation. This underscores the role of inflammation in thrombosis driven by the JAK2V617F mutation.</p>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"109236"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802298","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":"Effect of hypofibrinolysis on clinical outcomes of patients with septic disseminated intravascular coagulation.","authors":"Hiroyuki Koami, Yuichiro Sakamoto, Yuri Hirota, Akira Sasaki, Hirotaka Ogawa, Yutaro Furukawa, Ayaka Matsuoka, Kota Shinada, Kento Nakayama, Ryota Sakurai, Sachiko Iwanaga, Takayuki Onohara, Shogo Narumi, Mayuko Koba","doi":"10.1016/j.thromres.2024.109235","DOIUrl":"10.1016/j.thromres.2024.109235","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the utility of thromboelastometry (ROTEM) in assessing hypofibrinolysis among septic patients, specifically the association of hypofibrinolysis, as determined by ROTEM, with septic disseminated intravascular coagulation (DIC), organ dysfunction, and clinical outcomes.</p><p><strong>Methods: </strong>This single-center, retrospective analysis included adult septic patients admitted to Saga University Hospital from 2013 to 2017, with available ROTEM data. Hypofibrinolysis was assessed using the lysis index at 60 min (LI60) in extrinsic thromboelastometry (EXTEM). Based on their LI60 values, patients were classified into three groups: Hyper (LI60 ≤ 85), Normal (LI60 86-96), and Hypo (LI60 ≥ 97).</p><p><strong>Results: </strong>Among the 63 cases analyzed, the Hypo group showed significantly higher APACHEII and SOFA scores than the Normal group, indicating greater disease severity. Similarly, DIC and sepsis-induced coagulopathy (SIC) scores were notably higher in the Hypo group. The diagnostic performance of LI60 for ISTH-overt DIC showed an area under the curve (AUC) of 0.954, with an optimal cutoff value of 97 %, achieving 100 % sensitivity and 83.3 % specificity. The odds ratio for ISTH-overt DIC was 2.894, indicating a strong association between elevated LI60 and occurrence of DIC. Hypofibrinolysis predicted 28-day mortality and high SOFA scores (≥ 10) with high specificity and negative predictive value (NPV). A Kaplan-Meier curve revealed that the Hypo Group showed significantly worse clinical outcomes than the Normal and Hyper groups.</p><p><strong>Conclusion: </strong>For septic patients, fibrinolysis suppression presenting as \"hypofibrinolysis\" (elevated LI60) is associated with poor prognosis and risk of higher organ dysfunction. Moreover, it is a significant predictor of adverse clinical outcomes in sepsis.</p>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"109235"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792377","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":"Chemotherapy alters thrombomodulin and factor VIIIc expression resulting in acquired activated protein C resistance and enhanced thrombin generation in cancer associated thrombosis.","authors":"M P Ward, E M Ibrahim, S A O'Toole, Z Marchocki, J J O'Leary, F Abu Saadeh, L A Norris","doi":"10.1016/j.thromres.2024.109251","DOIUrl":"https://doi.org/10.1016/j.thromres.2024.109251","url":null,"abstract":"<p><strong>Background: </strong>Tumour type, treatment and patient related factors contribute to cancer associated venous thromboembolism (VTE), however, the role of each factor and the mechanisms involved are not understood.</p><p><strong>Aim: </strong>To assess the role of the tumour, and of chemotherapy, in mediating the procoagulant response associated with VTE in gynaecological cancer patients.</p><p><strong>Methods: </strong>Gynaecological cancer patients who developed VTE during follow-up (n = 59) (VTE+) were matched with treatment naïve(treatment (-)(VTE-)(n = 120) and chemotherapy treated patients(treatment (+)(VTE-) (n = 57)). Thrombin generation, Factor V(FV), VIIIc(FVIIIc), Tissue Factor Pathway Inhibitor(TFPI), soluble Thrombomodulin(sTM), Protein S(PS), C(PC) endothelial protein C receptor(EPCR) and fibrinogen were compared in each group. EPCR and TM expression was assessed in EA.hy926 cells in vitro following addition of chemotherapy agents. mRNA expression of coagulation genes was measured in tumour biopsies.</p><p><strong>Results: </strong>Thrombin generation was increased in treatment(-)VTE(+) compared with treatment(-)VTE(-) controls but not in the treatment(+)VTE(+) patients. Using the TM modified assay, thrombin generation was increased in the treatment (+)VTE(-) group compared with treatment(-)(VTE-) with a further increase in the treatment (+) VTE(+) group. Reduced levels of sTM in treatment (+) VTE(+) patients correlated with thrombin generation. TM expression was reduced in vitro by carboplatin and paclitaxel. FVIIIc was increased in both VTE groups and was predictive of VTE. F5 mRNA levels were lower in tumours from VTE(+) patients compared with controls.</p><p><strong>Conclusion: </strong>Chemotherapy alters sTM and confers an acquired activated Protein C(aPC) resistance which may be implicated in cancer associated VTE in gynaecological cancer patients. FVIIIc may be a useful predictive marker for VTE in cancer patients in this setting.</p>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"246 ","pages":"109251"},"PeriodicalIF":3.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967047","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":"Thromboembolic events associated with immune checkpoint inhibitors in cancer patients: A Bayesian network meta-analysis.","authors":"Jinhe Lin, Wenxing Li, Xin Zhang, Kai Zhou, Yanqi Yang, Shaoli Cheng, Ruifang Sun, Chengxue Dang, Dongmei Diao","doi":"10.1016/j.thromres.2024.109243","DOIUrl":"https://doi.org/10.1016/j.thromres.2024.109243","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs), which offer previously unknown therapeutic advantages, have revolutionized cancer treatment. However, the risk of thromboembolic events (TEEs) associated with ICIs remains unclear. The aim of this network meta-analysis (NMA) was to evaluate the incidence of TEEs in cancer patients receiving different treatment regimens.</p><p><strong>Methods: </strong>We searched for randomized clinical trials (RCTs) between January 2021 and December 2023 without restricting the cancer type. The percentages of TEEs were systematically extracted. An NMA was performed comparing atezolizumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, conventional therapy (which consists mainly of chemotherapy, targeted therapy, placebo, and their combinations), two ICI drugs, one ICI drug combined with conventional therapy, and two ICI drugs combined with conventional therapy. Additionally, subgroup analysis was conducted based on cancer type.</p><p><strong>Results: </strong>Eighty-three RCTs involving 54,736 patients were included. Patients receiving ICIs demonstrated comparable risks of arterial thromboembolism (ATE), deep vein thrombosis (DVT), myocardial infarction (MI), and cerebrovascular accidents (CVAs). Nivolumab (OR 0.39, 95 % CI 0.19 to 0.80) and two ICI drugs (OR 0.52, 95 % CI 0.29 to 0.89) had the lowest risk of venous thromboembolism (VTE) compared to two ICI drugs with conventional therapy. The risk of pulmonary embolism (PE) was greater for ipilimumab (OR 4.09, 95 % CI 1.13 to 15.51) than for nivolumab. For melanoma in the subgroup analysis, nivolumab significantly reduced the risk of VTE (OR 0.07, 95 % CI 0.00 to 0.76) compared to two ICI drugs. Among the single-ICI regimens, durvalumab was associated with the highest incidence of ATE, MI, and CVAs; ipilimumab had the highest incidence of VTE and PE; and pembrolizumab had the highest incidence of DVT. The combination of one ICI drug with conventional therapy was associated with a significantly greater risk of TEEs (except for MI) than the combination of two ICI drugs.</p><p><strong>Conclusions: </strong>Various ICI regimens in cancer patients exhibit clinically significant differences in the risks of TEEs. Nivolumab exhibited a favorable safety profile regarding VTE, while ipilimumab had the highest risk of both VTE and PE. Different ICI regimens require tailored risk management strategies to reduce TEEs.</p>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"246 ","pages":"109243"},"PeriodicalIF":3.7,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898306","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":"Tumor gene expression is associated with venous thromboembolism in patients with ductal pancreatic adenocarcinoma.","authors":"Floris T M Bosch, Frederike Dijk, Saskia Briedé, Jesse V Groen, Randa G Hanna-Sawires, Hans Halfwerk, Frederikus A Klok, Karin A H Kaasjager, Lodewijk A A Brosens, Quintus Molenaar, Bert A Bonsing, Sven Mieog, Marc G Besselink, Olivier R Busch, Joanne Verheij, Arantza Farina Sarasqueta, Hanneke W Wilmink, Jan Koster, Maarten F Bijlsma, Henri H Versteeg, Nick van Es, Jeroen T Buijs","doi":"10.1016/j.thromres.2024.109240","DOIUrl":"https://doi.org/10.1016/j.thromres.2024.109240","url":null,"abstract":"<p><strong>Introduction: </strong>In patients with pancreatic cancer, the risk of venous thromboembolism (VTE) is high compared to other cancer types, suggesting that tumor-intrinsic features drive hypercoagulability. Tumor gene expression analysis may help unravel the pathogenesis of VTE in these patients and help to identify high-risk patients.</p><p><strong>Aim: </strong>To evaluate the association between tumor gene expression patterns and VTE in patients with pancreatic cancer.</p><p><strong>Methods: </strong>In this retrospective cohort study RNA-sequence data from surgically resected tumor material from patients with pancreatic ductal adenocarcinoma (PDAC) was used to identify genes associated with the presence of venous thromboembolism (i.e., pulmonary embolism or deep-vein thrombosis) within one year follow-up after surgery. Additionally, VTE risk and expression of coagulation related genes in two molecular subtypes of pancreatic cancer was assessed.</p><p><strong>Results: </strong>Out of 151 patients, 10 (6.6 %) developed deep-vein thrombosis or pulmonary embolism within one year follow-up. Differential expression analysis yielded 89 genes significantly differentially expressed in patients with VTE compared to those without VTE, including ATP6V0A4, SYT14 and ZNF114. The incidence of VTE in classical subtype was higher (n = 9; 7.6 %) than in basal-like subtype (n = 1;4 %), but this difference was not statistically significant (SHR 1.79; 95 % CI 0.22-14.3). Forty-two coagulation-associated genes were identified that were differentially expressed between these molecular subtypes, including F5, PLAU, SERPINE1, and C4BPB.</p><p><strong>Conclusions: </strong>Patients with pancreatic cancer and VTE show a different tumor gene expression profile than those without VTE. Multiple coagulation-related genes were differentially expressed in classical versus basal-like molecular subtype, suggesting that there is a difference in pro-thrombotic phenotype.</p>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"246 ","pages":"109240"},"PeriodicalIF":3.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898307","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":"Risk of bleeding in pulmonary embolism patients concomitant with COVID-19 undergoing extended anticoagulation: A multicenter cohort study.","authors":"Yishan Li, Linfeng Xi, Dingyi Wang, Guohui Fan, Xincheng Li, Yiwei Shi, Hong Chen, Chaosheng Deng, Hong Chen, Qin Luo, Zhe Cheng, Shuai Zhang, Zhu Zhang, Yunxia Zhang, Qian Gao, Qiang Huang, Wanmu Xie, Zhenguo Zhai, Chen Wang","doi":"10.1016/j.thromres.2024.109237","DOIUrl":"https://doi.org/10.1016/j.thromres.2024.109237","url":null,"abstract":"<p><strong>Introduction: </strong>The impact of Coronavirus disease 2019 (COVID-19) on clinical outcomes in pulmonary embolism (PE) patients receiving extended anticoagulation therapy is not fully understood. The study aimed to investigate the impact of the Omicron outbreak on patients with PE receiving extended anticoagulation therapy.</p><p><strong>Materials and methods: </strong>This prospective multicenter cohort study was conducted during the Omicron pandemic. Patients diagnosed with PE between January 1, 2016, and September 1, 2022, who were on extended anticoagulation therapy, were recruited. The study compared VTE recurrence and bleeding events between COVID-19 and non-COVID-19 patients, using the propensity score weighting with overlap weights (PSOW) method for the final analysis.</p><p><strong>Results: </strong>A total of 521 patients with PE receiving extended anticoagulation therapy were enrolled. Patients suffering from COVID-19 had significantly higher bleeding rates (10.5 % vs 2.1 %, p = 0.001), with consistent results after PSOW (OR = 4.79, 95%CI [1.04-22.21], p = 0.045). No significant differences in VTE recurrence were observed between these two groups before and after weighting. During follow-up, 31 % of patients developed long COVID, with higher bleeding rates (14.6 % vs 3.5 %, p < 0.001). After PSOW, there was a significantly increased bleeding risk in patients with long COVID (HR = 3.29, 95%CI [1.28, 8.49]); Log-Rank test p < 0.001). Furthermore, a prior history of active malignancy (OR = 9.3; 95%CI [1.38, 59.98]), chronic kidney disease (OR = 13.98; 95%CI [1.59, 122.27]) and bleeding occurred during the acute phase of COVID-19 (OR = 23.73; 95%CI [5.20, 108.35]) were independent predictors of bleeding in patients with long COVID.</p><p><strong>Conclusions: </strong>COVID-19 and long COVID are associated with an increased bleeding risk in PE patients undergoing extended anticoagulation therapy. This study emphasizes the need for close monitoring and optimization of anticoagulation strategies in PE patients.</p>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"246 ","pages":"109237"},"PeriodicalIF":3.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886044","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":"Effectiveness of rehabilitation programmes targeting quality of life, psychological wellbeing, and functional capacity in pulmonary embolism survivors; a systematic review and best evidence synthesis.","authors":"Caoimhe Kenny, Olive Lennon, Frederikus A Klok, James Matthews, Fionnuala Ni Ainle, Rachel Rosovsky, Grainne O Donoghue","doi":"10.1016/j.thromres.2024.109242","DOIUrl":"https://doi.org/10.1016/j.thromres.2024.109242","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Half of people post pulmonary embolism (PE) experience ongoing symptoms such as dyspnoea, anxiety and depression, exercise limitation and fatigue. These symptoms can reduce their quality of life (QoL), psychological wellbeing, and functional capacity. The efficacy of rehabilitation interventions to prevent and manage these symptoms has not been established. The objectives of this review were to synthesise the evidence on interventions targeting QoL, psychological wellbeing, and functional capacity post PE, and to identify intervention characteristics and behaviour change techniques (BCTs) that contribute to successful rehabilitation programmes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The PRISMA reporting guidelines were followed. Five electronic databases were searched; PubMED, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PsycINFO. Searching began in November 2023, with the final search run in December 2023. Studies using experimental designs, in adult populations, employing rehabilitation programmes to target patient outcomes post PE were included. The Template of Intervention Description and Replication (TIDieR) 12 item checklist was used to score the description and replicability of the intervention and control conditions and the BCT taxonomy V1 was used to identify BCTs across the included interventions. Data was extracted and a best evidence synthesis was conducted.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 7321 studies identified, 12 studies (n = 648 participants) met the inclusion criteria; four randomised controlled trials (RCTs), one pilot RCT study and seven prospective cohort studies, all conducted at different timepoints in the disease course, using different selection criteria and with different interventions. Eight of the 12 included studies were evaluated as being of low quality based on the Effective Public Health Practice Project (EPHPP) tool. The mean TIDieR score was six out of 24 for intervention completeness and reporting. Twenty five BCTs were identified across the included studies, three of which were identified in all studies (\"Instruction on how to perform the behaviour\", \"demonstration of the behaviour\" and \"behaviour practice/ rehearsal\"). Overall the best evidence synthesis provided a mixed level of evidence for the effectiveness of rehabilitation interventions post PE. There is a limited level of evidence that rehabilitation has a positive effect on patient perceived QoL and inconsistent evidence that rehabilitation has any effect on psychological wellbeing. There is however, a moderate level of evidence to support the effectiveness of rehabilitation when it comes to improving functional capacity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This review highlights heterogeneity across available studies and provides some evidence supporting rehabilitation programmes to improve functional capacity in people living post PE. ","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"246 ","pages":"109242"},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898215","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":"PDPN/CLEC-2 axis modulates megakaryocyte subtypes in a hematopoietic stem cell-regulating megakaryocyte-dominant manner","authors":"Rikuto Nara ,&nbsp;Hinako Notoh ,&nbsp;Tomoyuki Sasaki ,&nbsp;Nagaharu Tsukiji ,&nbsp;Toshiaki Shirai ,&nbsp;Ayuka Kamata ,&nbsp;Nobuaki Suzuki ,&nbsp;Atsuo Suzuki ,&nbsp;Shuichi Okamoto ,&nbsp;Takeshi Kanematsu ,&nbsp;Naruko Suzuki ,&nbsp;Akira Katsumi ,&nbsp;Tetsuhito Kojima ,&nbsp;Katsue Suzuki-Inoue ,&nbsp;Tadashi Matsushita ,&nbsp;Shogo Tamura","doi":"10.1016/j.thromres.2024.109230","DOIUrl":"10.1016/j.thromres.2024.109230","url":null,"abstract":"<div><h3>Introduction</h3><div>Megakaryocytes are classified into several subtypes including LSP1-positive immune-skewed, MYLK4-positive hematopoietic stem cell (HSC)-regulating, and BMAL1-positive platelet-producing megakaryocytes. Podoplanin (PDPN)-expressing stromal cells generate a microenvironment that promotes megakaryopoiesis in the bone marrow. In this context, PDPN interacts with C-type lectin-like receptor-2 (CLEC-2) on megakaryocyte progenitors, which induces megakaryocyte proliferation. However, the megakaryocyte subtypes developed by the regulation of the PDPN/CLEC-2 axis have not yet been elucidated.</div></div><div><h3>Materials and methods</h3><div>We established an immortalized bone marrow PDPN-expressing stromal cell line and a PDPN-knockout line (PDPN WT and KO feeder cells, respectively). Bone marrow hematopoietic progenitors were committed to megakaryocytes in co-culture with PDPN WT or KO feeder cells. The number and ploidy of megakaryocytes, resultant platelets, and the polarization of megakaryocyte subtypes were investigated.</div></div><div><h3>Results</h3><div>The number of megakaryocytes was significantly increased in the co-culture with PDPN WT feeder cells compared to that with PDPN KO feeder cells. The megakaryocytes on the PDPN WT and KO feeders showed their main ploidy at 16 N∼32 N and 8 N∼16 N, respectively. The number of platelets was decreased in the co-culture with the PDPN WT feeder compared to that in the co-culture with the PDPN KO feeder. For each megakaryocyte subtype, the percentage of MYLK4-positive megakaryocytes significantly increased and the percentage of BMAL1-positive megakaryocytes significantly decreased when co-cultured with the PDPN WT feeder. These results were also confirmed in the co-culture of CLEC-2 conditional KO megakaryocytes with PDPN WT feeder cells.</div></div><div><h3>Conclusion</h3><div>The PDPN/CLEC-2 axis modulates megakaryocyte subtype differentiation, with a predominance of HSC-regulating megakaryocytes.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109230"},"PeriodicalIF":3.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of low-dose acetylsalicylic acid for the prevention of thromboembolic events in individuals positive for antiphospholipid antibodies: A systematic review and meta-analysis","authors":"Federica De Pascali ,&nbsp;Yulia Aleksandrovna Filippova ,&nbsp;Marco P. Donadini ,&nbsp;Vittorio Pengo ,&nbsp;Alessandro Squizzato","doi":"10.1016/j.thromres.2024.109225","DOIUrl":"10.1016/j.thromres.2024.109225","url":null,"abstract":"<div><h3>Background</h3><div>Anti-Phospholipid Antibodies (aPL) are autoantibodies predisposing to an increased risk of thrombotic events. The net clinical benefit of antithrombotic prophylaxis in aPL carriers is still unclear. We performed a systematic review to assess the efficacy and safety of antiplatelet drugs for the primary prevention of thrombotic events in aPL carriers.</div></div><div><h3>Methods</h3><div>Studies were identified by electronic search of MEDLINE and EMBASE database until May 2023. The differences in the outcomes among groups were estimated as pooled odds ratio (OR) and corresponding 95 % confidence interval (CI). Statistical heterogeneity was evaluated using the I2 statistic.</div></div><div><h3>Results</h3><div>1056 participants were included in 10 studies, 2 RCTs and 8 cohorts. Low-dose acetylsalicylic acid (LDA) was the antiplatelet drug in treated patients. Thrombotic events were significantly reduced in the LDA group compared to the control group [OR 0.46 (95 % CI 0.30–0.71), I2 27%, fixed-effects model]. Arterial thrombotic events were significantly reduced in the LDA group compared to the control group [OR 0.47 (95 % CI 0.26–0.86), I2 0%, fixed-effects model]. Venous thrombotic events were significantly reduced in the LDA group compared to the control group [OR 0.44 (95 % CI 0.21–0.89, I2 1%, fixed-effects model]. No major bleedings occurred in the five studies reporting them.</div></div><div><h3>Conclusions</h3><div>aPL carriers receiving long-term LDA had a significant reduction of thrombotic events, without a significant increase of the risk of major bleeding. It remains unclear if LDA has the same benefit/risk profile in all aPL profile, i.e. single, double, or triple positivity.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109225"},"PeriodicalIF":3.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702847","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":"Lupus-associated hypoprothrombinemia syndrome in children: Differences between post-infectious and autoimmune forms","authors":"Zighed Hanna ,&nbsp;Huguenin Yoann ,&nbsp;Blanc Laurence ,&nbsp;Valentin Jean-Baptiste ,&nbsp;Babuty Antoine ,&nbsp;Cussac Vincent ,&nbsp;Heritier Sebastien ,&nbsp;Biron-Andreani Christine ,&nbsp;Jeziorski Eric ,&nbsp;Moulis Lionel ,&nbsp;Harroche Annie ,&nbsp;Theron Alexandre","doi":"10.1016/j.thromres.2024.109231","DOIUrl":"10.1016/j.thromres.2024.109231","url":null,"abstract":"<div><h3>Introduction</h3><div>Lupus-anticoagulant hypoprothrombinemia syndrome (LAHS) is a rare but potentially serious condition. LAHS can be of post-infectious (PI) or autoimmune (AI) origin. However, there is currently no clear data available on the differences between these two forms.</div></div><div><h3>Method</h3><div>A retrospective multicenter study of cases in France was performed, followed by a review of cases in the literature.</div></div><div><h3>Result</h3><div>A total of 84 patients were included in the study. Seventeen patients were selected from the French cohort, and 67 were selected from a systematic review of the literature. 95 % of patients presented with hemorrhagic symptoms, with nearly half of these cases being severe. PI or AI context was identified in 33 % and 53 % of cases. 54 % of patients were treated with corticosteroids, and 30 % received immunomodulatory therapy. Thrombopenia and lower factor V were associated with a higher risk of bleeding. The AI group consisted of older children and exhibited significantly more severe bleeding (<em>p</em> &lt; 0.001). The treatment was more frequent and intensive, and the relapse rate was higher in the AI group (p &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Post-infectious forms are transient and associated with a low risk of serious hemorrhage. The treatment must be adapted according to the clinical and biological context.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109231"},"PeriodicalIF":3.7,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702848","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}