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Efficacy and safety of anticoagulant for treatment and prophylaxis of VTE patients with renal insufficiency: a systemic review and meta-analysis 抗凝剂治疗和预防肾功能不全 VTE 患者的有效性和安全性:系统回顾和荟萃分析
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-02-05 DOI: 10.1186/s12959-023-00576-2
Shuangshuang Ma, Guohui Fan, Feiya Xu, Xiaomeng Zhang, Yinong Chen, Yuzhi Tao, Yishan Li, Yanshuang Lyu, Peiran Yang, Dingyi Wang, Zhenguo Zhai, Chen Wang
Patients with venous thromboembolism (VTE) comorbid renal insufficiency (RI) are at higher risk of bleeding and thrombosis. Recommendations in guidelines on anticoagulation therapy for those patients remain ambiguous. The goal of this study is to compare the efficacy and safety between different anticoagulant regimens in VTE patients comorbid RI at different stages of treatment and prophylaxis. We performed English-language searches of Pubmed, EMBASE, and Web of Science (inception to Nov 2022). RCTs evaluated anticoagulants for VTE treatment at the acute phase, extension phase, and prophylaxis in patients with RI and reported efficacy and safety outcomes were selected. The methodological quality of the studies was assessed at the outcome level using the risk-of-bias assessment tool developed by the Cochrane Bias Methods Group. A meta-analysis of twenty-five RCTs was conducted, comprising data from twenty-three articles, encompassing a total of 9,680 participants with RI. In the acute phase, the risk of bleeding was increased with novel oral anticoagulants (NOACs) compared to LMWH (RR 1.29, 95% CI 1.04–1.60). For the prophylaxis of VTE, NOACs were associated with an elevated risk of bleeding compared with placebo (RR 1.31, 95%CI 1.02–1.68). In comparison to non-RI patients, both NOACs and vitamin K antagonists (VKA) could increase the risk of bleeding among RI patients (RR 1.45, 95%CI 1.14–1.84 and RR 1.53, 95%CI 1.25–1.88, respectively) during acute phase, while NOACs may increase the incidence of VTE in RI population (RR 1.74, 95%CI 1.29–2.34). RI patients who are under routine anticoagulation have a significantly higher risk of adverse outcomes. LMWH is the most effective and safe option for VTE treatment or prophylaxis in patients with RI. • Renal insufficient (RI) patients were at significant higher risk of adverse outcomes, especially bleeding, than non-RI patients under the use of routine anticoagulation treatment. • Low molecular weight heparin (LWMH) would be an optimized option for patients with RI undergoing VTE treatment and prophylaxis, both in terms of efficacy and safety. • These findings provide comprehensive evidence for the optimal choice of anticoagulants for the treatment and prevention of VTE in patients with comorbid RI.
静脉血栓栓塞症(VTE)合并肾功能不全(RI)的患者出血和血栓形成的风险较高。指南中关于这些患者抗凝治疗的建议仍不明确。本研究旨在比较不同抗凝治疗方案对合并 RI 的 VTE 患者在不同治疗和预防阶段的疗效和安全性。我们对 Pubmed、EMBASE 和 Web of Science 进行了英文检索(起始时间至 2022 年 11 月)。我们选择了评估抗凝药物在 RI 患者急性期、延长期和预防期治疗 VTE 的研究,并报告了疗效和安全性结果。在结果层面上,采用 Cochrane 偏倚方法小组开发的偏倚风险评估工具对研究的方法学质量进行了评估。我们对 25 项 RCT 进行了荟萃分析,其中包括 23 篇文章的数据,共涉及 9,680 名 RI 患者。在急性期,新型口服抗凝药(NOACs)的出血风险比 LMWH 高(RR 1.29,95% CI 1.04-1.60)。在预防 VTE 方面,与安慰剂相比,NOAC 的出血风险升高(RR 1.31,95%CI 1.02-1.68)。与非 RI 患者相比,在急性期,NOACs 和维生素 K 拮抗剂(VKA)都会增加 RI 患者的出血风险(RR 分别为 1.45,95%CI 1.14-1.84 和 RR 1.53,95%CI 1.25-1.88),而 NOACs 可能会增加 RI 患者的 VTE 发生率(RR 1.74,95%CI 1.29-2.34)。接受常规抗凝治疗的 RI 患者发生不良后果的风险明显更高。LMWH 是治疗或预防 RI 患者 VTE 的最有效、最安全的选择。- 与接受常规抗凝治疗的非肾功能不全(RI)患者相比,肾功能不全(RI)患者发生不良后果(尤其是出血)的风险明显更高。- 对于接受 VTE 治疗和预防的 RI 患者来说,低分子量肝素(LWMH)在疗效和安全性方面都是一个最佳选择。- 这些研究结果为合并 RI 患者治疗和预防 VTE 的最佳抗凝药物选择提供了全面的证据。
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引用次数: 0
Causes of death after first time venous thromboembolism 首次静脉血栓栓塞后的死亡原因
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-02-01 DOI: 10.1186/s12959-024-00586-8
Frida Lonnberg, Andreas Roos, Maria Farm, André Heurlin, Mantas Okas, Bruna Gigante, Anwar J Siddiqui
Causes of death after first time community-acquired venous thromboembolism (VTE) diagnosed in unselected patients at the emergency department (ED) was investigated. The study consists of all patients > 18 years of age who had a visit for any medical reason to any of 5 different ED in Stockholm County, Sweden from 1st January 2016 to 31st December 2017. We have identified all patients with a first registered incident VTE; deep vein thrombosis (DVT) and/or pulmonary embolism (PE) during the study period. Cox regression models were used to estimate hazards ratios (HR) with 95% confidence intervals (CIs) for all-cause mortality and cause-specific death in patients with DVT or PE using all other patients as the reference group. In total, 359,884 patients had an ED visit during the study period of whom about 2.1% were diagnosed with VTE (DVT = 4,384, PE = 3,212). The patients with VTE were older compared to the control group. During a mean follow up of 2.1 years, 1567 (21%) and 23,741(6.7%) patients died within the VTE and reference group, respectively. The adjusted risk of all-cause mortality was nearly double in patients with DVT (HR 1.7; 95% CI, 1.5–1.8) and more than 3-fold in patients with PE (HR 3.4; 95% CI, 3.1–3.6). While the risk of cancer related death was nearly 3-fold in patient with DVT (HR 2.7; 95% CI, 2.4–3.1), and 5-fold in PE (HR 5.4; 95% CI, 4.9-6.0 respectively). The diagnosis of PE during the ED visit was associated with a significantly higher risk of cardiovascular death (HR 2.2; 95% CI, 1.9–2.6). Patients with VTE have an elevated risk of all-cause mortality, including cardiovascular death.
该研究调查了急诊科(ED)未入选患者首次诊断为社区获得性静脉血栓栓塞症(VTE)后的死亡原因。研究对象包括2016年1月1日至2017年12月31日期间因任何医疗原因在瑞典斯德哥尔摩郡5个不同急诊科中的任何一个就诊的所有年龄大于18岁的患者。我们确定了所有在研究期间首次登记发生 VTE(深静脉血栓 (DVT) 和/或肺栓塞 (PE))的患者。我们使用 Cox 回归模型估算了深静脉血栓形成或肺栓塞患者的全因死亡率和特定原因死亡的危险比 (HR),并将所有其他患者作为参照组,得出了 95% 的置信区间 (CI)。在研究期间,共有359884名患者在急诊室就诊,其中约2.1%的患者被诊断为VTE(深静脉血栓=4384人,PE=3212人)。与对照组相比,VTE 患者的年龄更大。在平均 2.1 年的随访期间,VTE 组和参照组分别有 1567 名(21%)和 23741 名(6.7%)患者死亡。调整后,深静脉血栓患者的全因死亡风险几乎是对照组的两倍(HR 1.7;95% CI,1.5-1.8),而 PE 患者的全因死亡风险是对照组的三倍多(HR 3.4;95% CI,3.1-3.6)。而深静脉血栓患者的癌症相关死亡风险是深静脉血栓患者的近3倍(HR 2.7;95% CI,2.4-3.1),是PE患者的5倍(HR 5.4;95% CI,4.9-6.0)。在急诊室就诊时诊断出 PE 与心血管死亡风险显著升高有关(HR 2.2;95% CI,1.9-2.6)。VTE 患者全因死亡(包括心血管死亡)的风险较高。
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引用次数: 0
Nomogram for hospital-acquired venous thromboembolism among patients with cardiovascular diseases 心血管疾病患者医院获得性静脉血栓栓塞症的提名图
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-01-30 DOI: 10.1186/s12959-024-00584-w
Qin Luo, Xin Li, Zhihui Zhao, Qing Zhao, Zhihong Liu, Weixian Yang
Identifying venous thromboembolism (VTE) is challenging for patients with cardiovascular diseases due to similar clinical presentation. Most hospital-acquired VTE events are preventable, whereas the implementation of VTE prophylaxis in clinical practice is far from sufficient. There is a lack of hospital-acquired VTE prediction models tailored specifically designed for patients with cardiovascular diseases. We aimed to develop a nomogram predicting hospital-acquired VTE specifically for patients with cardiovascular diseases. Consecutive patients with cardiovascular diseases admitted to internal medicine of Fuwai hospital between September 2020 and August 2021 were included. Univariable and multivariable logistic regression were applied to identify risk factors of hospital-acquired VTE. A nomogram was constructed according to multivariable logistic regression, and internally validated by bootstrapping. A total of 27,235 patients were included. During a median hospitalization of four days, 154 (0.57%) patients developed hospital-acquired VTE. Multivariable logistic regression identified that female sex, age, infection, pulmonary hypertension, obstructive sleep apnea, acute coronary syndrome, cardiomyopathy, heart failure, immobility, central venous catheter, intra-aortic balloon pump and anticoagulation were independently associated with hospital-acquired VTE. The nomogram was constructed with high accuracy in both the training set and validation (concordance index 0.865 in the training set, and 0.864 in validation), which was further confirmed in calibration. Compared to Padua model, the Fuwai model demonstrated significantly better discrimination ability (area under curve 0.865 vs. 0.786, net reclassification index 0.052, 95% confidence interval 0.012–0.091, P = 0.009; integrated discrimination index 0.020, 95% confidence interval 0.001–0.039, P = 0.051). The incidence of hospital-acquired VTE in patients with cardiovascular diseases is relatively low. The nomogram exhibits high accuracy in predicting hospital-acquired VTE in patients with cardiovascular diseases.
由于临床表现相似,对于心血管疾病患者来说,识别静脉血栓栓塞症(VTE)是一项挑战。大多数医院获得性 VTE 事件是可以预防的,而临床实践中 VTE 预防措施的实施远远不够。目前缺乏专门针对心血管疾病患者的医院获得性 VTE 预测模型。我们的目标是开发一种专门针对心血管疾病患者的医院获得性 VTE 预测提名图。我们纳入了 2020 年 9 月至 2021 年 8 月期间阜外医院内科收治的心血管疾病患者。应用单变量和多变量逻辑回归确定医院获得性 VTE 的风险因素。根据多变量逻辑回归构建了提名图,并通过引导法进行了内部验证。共纳入 27235 名患者。在中位 4 天的住院期间,154 名患者(0.57%)发生了医院获得性 VTE。多变量逻辑回归发现,女性性别、年龄、感染、肺动脉高压、阻塞性睡眠呼吸暂停、急性冠状动脉综合征、心肌病、心力衰竭、行动不便、中心静脉导管、主动脉内球囊泵和抗凝与医院获得性 VTE 独立相关。所构建的提名图在训练集和验证中都具有很高的准确性(训练集中的一致性指数为 0.865,验证中的一致性指数为 0.864),这一点在校准中得到了进一步证实。与帕多瓦模型相比,阜外模型的分辨能力明显更强(曲线下面积 0.865 vs. 0.786,净再分类指数 0.052,95% 置信区间 0.012-0.091,P = 0.009;综合分辨指数 0.020,95% 置信区间 0.001-0.039,P = 0.051)。心血管疾病患者在医院获得性 VTE 的发生率相对较低。该提名图在预测心血管疾病患者的医院获得性 VTE 方面具有很高的准确性。
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引用次数: 0
Detecting prokaryote-specific gene and other bacterial signatures in thrombi from patients with acute ischemic stroke. 检测急性缺血性中风患者血栓中的原核细胞特异基因和其他细菌特征。
IF 2.6 4区 医学 Q2 HEMATOLOGY Pub Date : 2024-01-23 DOI: 10.1186/s12959-024-00583-x
Xiaoke Wang, Jie Gao, Yantong Chen, Xiaohao Zhang, Zhengze Dai, Qiliang Dai, Mengna Peng, Lulu Xiao, Xuerong Jia, Haodi Cai, Tao Mou, Xiang Li, Gelin Xu

Background and purpose: Microbial infection has been associated with thrombogenesis. This study aimed to detect bacterium-specific genes and other signatures in thrombi from patients with acute ischemic stroke and to relate these signatures to clinical characteristics.

Methods: Blood samples were collected before thrombectomy procedures, and thrombus samples were obtained during the procedure. Identification and classification of bacteria in the samples were accomplished using 16 S rRNA gene sequencing. Bacterium-specific structures were observed with transmission electron microscopy. Bacterium-specific biomarkers were detected through immunohistochemical staining.

Results: 16 S rRNA gene was detected in 32.1% of the thrombus samples from 81 patients. Bacillus (0.04% vs. 0.00046%, p = 0.003), Parabacteroides (0.20% vs. 0.09%, p = 0.029), Prevotella (1.57% vs. 0.38%, p = 0.010), Streptococcus (1.53% vs. 0.29%, p = 0.001), Romboutsia (0.18% vs. 0.0070%, p = 0.029), Corynebacterium (1.61% vs. 1.26%, p = 0.026) and Roseburia (0.53% vs. 0.05%, p = 0.005) exhibited significantly higher abundance in thrombi compared to arterial blood. Bacteria-like structures were observed in 22 (27.1%), while whole bacteria-like structures were observed in 7 (8.6%) thrombi under transmission electron microscopy. Immunohistochemical staining detected bacterium-specific monocyte/macrophage markers in 51 (63.0%) out of 81 thrombi. Logistic regression analysis indicated that alcohol consumption was associated with a higher bacteria burden in thrombi (odds ratio = 3.19; 95% CI, 1.10-9.27; p = 0.033).

Conclusion: Bacterial signatures usually found in the oral cavity and digestive tract were detected in thrombi from patients with ischemic stroke. This suggests a potential involvement of bacterial infection in the development of thrombosis. Long-term alcohol consumption may potentially enhance this possibility.

背景和目的:微生物感染与血栓形成有关。本研究旨在检测急性缺血性脑卒中患者血栓中的细菌特异性基因和其他特征,并将这些特征与临床特征联系起来:方法:在血栓切除术前采集血液样本,在手术过程中采集血栓样本。采用 16 S rRNA 基因测序法对样本中的细菌进行鉴定和分类。用透射电子显微镜观察细菌的特异性结构。通过免疫组化染色检测细菌特异性生物标记物:81名患者的血栓样本中有32.1%检测到16 S rRNA基因。芽孢杆菌(0.04% vs. 0.00046%,p = 0.003)、副杆菌(0.20% vs. 0.09%,p = 0.029)、前驱菌(1.57% vs. 0.38%,p = 0.010)、链球菌(1.53% vs. 0.29%,p = 0.001)、隆突菌(0.18% vs. 0.0070%,p = 0.029)、棒状杆菌(1.61% vs. 1.26%,p = 0.026)和蔷薇杆菌(0.53% vs. 0.05%,p = 0.005)在血栓中的含量明显高于动脉血。在透射电子显微镜下,22 个血栓(27.1%)中观察到细菌样结构,7 个血栓(8.6%)中观察到完整的细菌样结构。免疫组化染色在 81 个血栓中的 51 个(63.0%)中检测到细菌特异性单核细胞/巨噬细胞标记物。逻辑回归分析表明,饮酒与血栓中较高的细菌负荷有关(几率比=3.19;95% CI,1.10-9.27;P=0.033):结论:缺血性脑卒中患者的血栓中检测到了通常在口腔和消化道中发现的细菌特征。结论:在缺血性脑卒中患者的血栓中检测到了通常在口腔和消化道中发现的细菌特征,这表明细菌感染可能参与了血栓的形成。长期饮酒可能会增加这种可能性。
{"title":"Detecting prokaryote-specific gene and other bacterial signatures in thrombi from patients with acute ischemic stroke.","authors":"Xiaoke Wang, Jie Gao, Yantong Chen, Xiaohao Zhang, Zhengze Dai, Qiliang Dai, Mengna Peng, Lulu Xiao, Xuerong Jia, Haodi Cai, Tao Mou, Xiang Li, Gelin Xu","doi":"10.1186/s12959-024-00583-x","DOIUrl":"10.1186/s12959-024-00583-x","url":null,"abstract":"<p><strong>Background and purpose: </strong>Microbial infection has been associated with thrombogenesis. This study aimed to detect bacterium-specific genes and other signatures in thrombi from patients with acute ischemic stroke and to relate these signatures to clinical characteristics.</p><p><strong>Methods: </strong>Blood samples were collected before thrombectomy procedures, and thrombus samples were obtained during the procedure. Identification and classification of bacteria in the samples were accomplished using 16 S rRNA gene sequencing. Bacterium-specific structures were observed with transmission electron microscopy. Bacterium-specific biomarkers were detected through immunohistochemical staining.</p><p><strong>Results: </strong>16 S rRNA gene was detected in 32.1% of the thrombus samples from 81 patients. Bacillus (0.04% vs. 0.00046%, p = 0.003), Parabacteroides (0.20% vs. 0.09%, p = 0.029), Prevotella (1.57% vs. 0.38%, p = 0.010), Streptococcus (1.53% vs. 0.29%, p = 0.001), Romboutsia (0.18% vs. 0.0070%, p = 0.029), Corynebacterium (1.61% vs. 1.26%, p = 0.026) and Roseburia (0.53% vs. 0.05%, p = 0.005) exhibited significantly higher abundance in thrombi compared to arterial blood. Bacteria-like structures were observed in 22 (27.1%), while whole bacteria-like structures were observed in 7 (8.6%) thrombi under transmission electron microscopy. Immunohistochemical staining detected bacterium-specific monocyte/macrophage markers in 51 (63.0%) out of 81 thrombi. Logistic regression analysis indicated that alcohol consumption was associated with a higher bacteria burden in thrombi (odds ratio = 3.19; 95% CI, 1.10-9.27; p = 0.033).</p><p><strong>Conclusion: </strong>Bacterial signatures usually found in the oral cavity and digestive tract were detected in thrombi from patients with ischemic stroke. This suggests a potential involvement of bacterial infection in the development of thrombosis. Long-term alcohol consumption may potentially enhance this possibility.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543101","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}
引用次数: 0
Regulation of tissue factor activity by interaction with the first PDZ domain of MAGI1 通过与 MAGI1 的第一个 PDZ 结构域相互作用调节组织因子的活性
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-01-17 DOI: 10.1186/s12959-023-00580-6
Mohammad A. Mohammad, Sophie Featherby, Camille Ettelaie
Tissue factor (TF) activity is stringently regulated through processes termed encryption. Post-translational modification of TF and its interactions with various protein and lipid moieties allows for a multi-step de-encryption of TF and procoagulant activation. Membrane-associated guanylate kinase-with inverted configuration (MAGI) proteins are known to regulate the localisation and activity of a number of proteins including cell-surface receptors. The interaction of TF with MAGI1 protein was examined as a means of regulating TF activity. MDA-MB-231 cell line was used which express TF and MAGI1, and respond well to protease activated receptor (PAR)2 activation. Proximity ligation assay (PLA), co-immunoprecipitation and pull-down experiments were used to examine the interaction of TF with MAGI1-3 proteins and to investigate the influence of PAR2 activation. Furthermore, by cloning and expressing the PDZ domains from MAGI1, the TF-binding domain was identified. The ability of the recombinant PDZ domains to act as competitors for MAGI1, allowing the induction of TF procoagulant and signalling activity was then examined. PLA and fluorescence microscopic analysis indicated that TF predominantly associates with MAGI1 and less with MAGI2 and MAGI3 proteins. The interaction of TF with MAGI1 was also demonstrated by both co-immunoprecipitation of TF with MAGI1, and co-immunoprecipitation of MAGI1 with TF. Moreover, activation of PAR2 resulted in reduction in the association of these two proteins. Pull-down assays using TF-cytoplasmic domain peptides indicated that the phosphorylation of Ser253 within TF prevents its association with MAGI1. Additionally, the five HA-tagged PDZ domains of MAGI1 were overexpressed separately, and the putative TF-binding domain was identified as PDZ1 domain. Expression of this PDZ domain in cells significantly augmented the TF activity measured both as thrombin-generation and also TF-mediated proliferative signalling. Our data indicate a stabilising interaction between TF and the PDZ-1 domain of MAGI1 and demonstrate that the activation of PAR2 disrupts this interaction. The release of TF from MAGI1 appears to be an initial step in TF de-encryption, associated with increased TF-mediated procoagulant and signalling activities. This mechanism is also likely to lead to further interactions and modifications leading to further enhancement of procoagulant activity, or the release of TF.
组织因子(TF)的活性是通过所谓的加密过程严格调节的。TF 的翻译后修饰及其与各种蛋白质和脂质分子的相互作用可使 TF 经过多个步骤解除加密并促进凝血活化。众所周知,膜相关鸟苷酸激酶-倒置构型(MAGI)蛋白可调节包括细胞表面受体在内的多种蛋白的定位和活性。研究人员将 TF 与 MAGI1 蛋白的相互作用作为调节 TF 活性的一种手段。研究使用了表达 TF 和 MAGI1 的 MDA-MB-231 细胞系,它们对蛋白酶激活受体(PAR)2 的激活反应良好。实验采用了邻近连接试验(PLA)、共免疫沉淀和下拉实验来检测 TF 与 MAGI1-3 蛋白的相互作用,并研究 PAR2 激活的影响。此外,通过克隆和表达 MAGI1 的 PDZ 结构域,确定了 TF 结合结构域。然后研究了重组 PDZ 结构域作为 MAGI1 竞争者的能力,从而诱导 TF 促凝和信号活性。PLA 和荧光显微分析表明,TF 主要与 MAGI1 结合,与 MAGI2 和 MAGI3 蛋白的结合较少。TF 与 MAGI1 的共沉淀以及 MAGI1 与 TF 的共沉淀也证明了 TF 与 MAGI1 的相互作用。此外,PAR2 的激活会导致这两种蛋白的结合减少。使用 TF 细胞质结构域多肽进行的牵引试验表明,TF 内 Ser253 的磷酸化会阻止其与 MAGI1 的结合。此外,还分别过表达了 MAGI1 的五个 HA 标记 PDZ 结构域,并确定了推定的 TF 结合结构域为 PDZ1 结构域。在细胞中表达该 PDZ 结构域可显著增强 TF 活性,包括凝血酶生成和 TF 介导的增殖信号。我们的数据表明,TF 与 MAGI1 的 PDZ-1 结构域之间存在稳定的相互作用,并证明 PAR2 的激活会破坏这种相互作用。TF 从 MAGI1 中释放似乎是 TF 解密的第一步,这与 TF 介导的促凝血和信号活动增加有关。这一机制还可能导致进一步的相互作用和修饰,从而进一步增强促凝活性或释放 TF。
{"title":"Regulation of tissue factor activity by interaction with the first PDZ domain of MAGI1","authors":"Mohammad A. Mohammad, Sophie Featherby, Camille Ettelaie","doi":"10.1186/s12959-023-00580-6","DOIUrl":"https://doi.org/10.1186/s12959-023-00580-6","url":null,"abstract":"Tissue factor (TF) activity is stringently regulated through processes termed encryption. Post-translational modification of TF and its interactions with various protein and lipid moieties allows for a multi-step de-encryption of TF and procoagulant activation. Membrane-associated guanylate kinase-with inverted configuration (MAGI) proteins are known to regulate the localisation and activity of a number of proteins including cell-surface receptors. The interaction of TF with MAGI1 protein was examined as a means of regulating TF activity. MDA-MB-231 cell line was used which express TF and MAGI1, and respond well to protease activated receptor (PAR)2 activation. Proximity ligation assay (PLA), co-immunoprecipitation and pull-down experiments were used to examine the interaction of TF with MAGI1-3 proteins and to investigate the influence of PAR2 activation. Furthermore, by cloning and expressing the PDZ domains from MAGI1, the TF-binding domain was identified. The ability of the recombinant PDZ domains to act as competitors for MAGI1, allowing the induction of TF procoagulant and signalling activity was then examined. PLA and fluorescence microscopic analysis indicated that TF predominantly associates with MAGI1 and less with MAGI2 and MAGI3 proteins. The interaction of TF with MAGI1 was also demonstrated by both co-immunoprecipitation of TF with MAGI1, and co-immunoprecipitation of MAGI1 with TF. Moreover, activation of PAR2 resulted in reduction in the association of these two proteins. Pull-down assays using TF-cytoplasmic domain peptides indicated that the phosphorylation of Ser253 within TF prevents its association with MAGI1. Additionally, the five HA-tagged PDZ domains of MAGI1 were overexpressed separately, and the putative TF-binding domain was identified as PDZ1 domain. Expression of this PDZ domain in cells significantly augmented the TF activity measured both as thrombin-generation and also TF-mediated proliferative signalling. Our data indicate a stabilising interaction between TF and the PDZ-1 domain of MAGI1 and demonstrate that the activation of PAR2 disrupts this interaction. The release of TF from MAGI1 appears to be an initial step in TF de-encryption, associated with increased TF-mediated procoagulant and signalling activities. This mechanism is also likely to lead to further interactions and modifications leading to further enhancement of procoagulant activity, or the release of TF.","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139481665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spontaneous coronary artery dissection in a young patient with antiphospholipid syndrome 一名抗磷脂综合征年轻患者的自发性冠状动脉夹层
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-01-17 DOI: 10.1186/s12959-023-00573-5
Ai Phi Thuy Ho, Eirik Tjønnfjord, Oliver Meyerdierks, Ellen Elisabeth Brodin
A 28-year-old man diagnosed with triple positive antiphospholipid syndrome (APS) and undergoing warfarin experienced three separate admissions to the cardiac ward within a one-month period due to escalating chest pain. While the initial two admissions revealed normal results in cardiological investigations, such as blood tests, electrocardiogram, and echocardiography, the third admission unveiled signs of ST-elevation myocardial infarction (STEMI), despite the patient maintaining an INR (International Normalized Ratio) of 4. Subsequent percutaneous coronary intervention (PCI) exposed spontaneous coronary artery dissection (SCAD) of type 3. Faced with hemodynamic instability and worsening symptoms, the patient underwent stenting and was prescribed dual antiplatelet therapy in addition to warfarin. A follow-up evaluation one month later indicated a normalization of his condition.
一名被诊断为抗磷脂综合征(APS)三阳性并服用华法林的 28 岁男子因胸痛加剧,在一个月内三次入住心脏科病房。最初两次入院时,血液化验、心电图和超声心动图等心脏检查结果显示正常,而第三次入院时,尽管患者的 INR(国际正常化比值)保持在 4,但还是出现了 ST 段抬高型心肌梗死(STEMI)的迹象。面对血流动力学不稳定和不断恶化的症状,患者接受了支架植入术,并在华法林的基础上接受了双联抗血小板治疗。一个月后的随访评估表明,他的病情趋于正常。
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引用次数: 0
Factors influencing DVT formation in sepsis 影响败血症中深静脉血栓形成的因素
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-01-16 DOI: 10.1186/s12959-024-00582-y
Lu Wang, Xudong Ma, Yujie Chen, Sifa Gao, Wei Pan, Jieqing Chen, Longxiang Su, Huaiwu He, Yun Long, Chang Yin, Xiang Zhou
Sepsis is a global public health burden. Deep vein thrombosis (DVT) is the third most common cause of death from cardiovascular disease after heart attacks and strokes. We designed this experiment to investigate the factors influencing DVT formation in patients with sepsis. In this survey, 918 septic patients admitted to Peking Union Medical College Hospital, who underwent DVT screening were enrolled. The data were collected from June 8, 2013 to October 12, 2022. The differences between septic patients with and without DVT were studied from following aspects: basic information, comorbidities, inflammatory cytokines, albumin, source of infection, sequential organ failure assessment (SOFA) score, coagulation and prognosis. In this study, the prevalence of DVT in patients with sepsis was 0.23. Elderly patients with sepsis were prone to DVT (p value < 0.001). In terms of comorbidities, septic patients with hypertension and atrial fibrillation were prone to DVT (p value 0.045 and 0.048). Inflammatory cytokines, such as procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, had no significant correlation with DVT in patients with sepsis (p value 0.364, 0.882, 0.912, 0.789, 0.245, and 0.780). Levels of serum albumin correlated with DVT in patients with sepsis (p value 0.003). The SOFA total score had no relationship with DVT formation (p value 0.254). Coagulation and respiration function were negatively correlated with DVT (p value 0.018). Liver function was positively correlated with DVT (p value 0.020). Patients in the DVT group had longer duration of mechanical ventilation and longer intensive care unit (ICU) stays (p value < 0.001 and 0.006). There was no significant difference in survival in septic patients with and without DVT (p value 0.868). The SOFA total score had no relationship with DVT formation. The function of each organ had different effects on DVT formation. Better coagulation and respiration function, easier DVT formation. Poorer liver function, easier DVT formation. DVT was associated with longer duration of mechanical ventilation and longer ICU stays.
败血症是一项全球性的公共卫生负担。深静脉血栓(DVT)是继心脏病发作和中风之后导致心血管疾病死亡的第三大常见原因。我们设计了这项实验来研究影响败血症患者深静脉血栓形成的因素。本次调查共纳入了 918 名在北京协和医院住院并接受深静脉血栓筛查的败血症患者。数据收集时间为 2013 年 6 月 8 日至 2022 年 10 月 12 日。从基本信息、合并症、炎性细胞因子、白蛋白、感染来源、序贯器官功能衰竭评估(SOFA)评分、凝血功能和预后等方面研究了有深静脉血栓与无深静脉血栓脓毒症患者的差异。在这项研究中,脓毒症患者深静脉血栓的发病率为 0.23。老年败血症患者容易发生深静脉血栓(P值<0.001)。在合并症方面,患有高血压和心房颤动的脓毒症患者容易发生深静脉血栓(P 值为 0.045 和 0.048)。炎性细胞因子,如降钙素原(PCT)、C反应蛋白(CRP)、白细胞介素(IL)-6、IL-8、IL-10、肿瘤坏死因子(TNF)-α,与脓毒症患者深静脉血栓形成无明显相关性(P值分别为0.364、0.882、0.912、0.789、0.245和0.780)。脓毒症患者的血清白蛋白水平与深静脉血栓相关(p 值为 0.003)。SOFA 总分与深静脉血栓形成无关(P 值为 0.254)。凝血功能和呼吸功能与深静脉血栓呈负相关(p 值 0.018)。肝功能与深静脉血栓呈正相关(p 值 0.020)。深静脉血栓组患者的机械通气时间和重症监护室(ICU)停留时间较长(p 值分别小于 0.001 和 0.006)。有深静脉血栓和没有深静脉血栓的脓毒症患者在存活率方面没有明显差异(P值为0.868)。SOFA总分与深静脉血栓的形成没有关系。各器官的功能对深静脉血栓的形成有不同的影响。凝血和呼吸功能越好,深静脉血栓形成越容易。肝功能较差,深静脉血栓更容易形成。深静脉血栓与机械通气时间较长和重症监护室停留时间较长有关。
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引用次数: 0
Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis 抗凝血酶和凝血酶原联合疗法对败血症相关弥散性血管内凝血的影响:系统综述和荟萃分析
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-01-15 DOI: 10.1186/s12959-023-00579-z
Takaaki Totoki, Yuto Makino, Kazuma Yamakawa, Hiroyuki Koami, Takeshi Wada, Takashi Ito, Toshiaki Iba
Disseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) on DIC syndrome have previously been examined, the results are inconsistent and inconclusive. Therefore, we conducted a systematic review on the combined administration of AT and rTM for the treatment of septic DIC to investigate the superiority of the combination therapy over either AT or rTM monotherapy using a random-effects analysis model. We searched electronic databases, including Medline, Cochrane Central Register of Controlled Trials, Scopus, and Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web from inception to January 2022. Studies assessing the efficacy of combined AT and rTM were included. The primary outcome was all-cause mortality, and the secondary outcome was occurrence of serious bleeding complications compared to monotherapy. We presented the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) depending on reporting results in each primary study. We analyzed seven enrolled clinical trials, all of which were observational studies. Combination therapy had a non-significant favorable association with lower 28-day mortality compared to monotherapy (HR 0.67 [0.43–1.05], OR 0.73 [0.45–1.18]). The I2 values were 60% and 72%, respectively, suggesting high heterogeneity. As a secondary outcome, bleeding complications were similar between the two groups (pooled OR 1.11 [0.55–2.23], I2 value 55%). Although the findings in this analysis could not confirm a statistically significant effect of AT and rTM combination therapy for septic DIC, it showed a promising effect in terms of improving mortality. The incidence of bleeding was low and clinically feasible. Further research is warranted to draw more conclusive results. This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: 000049820).
弥散性血管内凝血(DIC)综合征是一种高度致命的疾病,其特点是并发多器官损伤。虽然以前曾研究过抗凝血酶(AT)和重组血栓调节蛋白(rTM)联合应用对 DIC 综合征的影响,但结果并不一致,也没有定论。因此,我们对联合应用 AT 和 rTM 治疗脓毒症 DIC 进行了系统性综述,采用随机效应分析模型研究联合疗法优于 AT 或 rTM 单药疗法。我们检索了从开始到 2022 年 1 月的电子数据库,包括 Medline、Cochrane Central Register of Controlled Trials、Scopus 和 Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web。纳入的研究评估了AT和rTM联合治疗的疗效。与单一疗法相比,主要结果是全因死亡率,次要结果是严重出血并发症的发生率。根据每项主要研究的报告结果,我们列出了汇总的几率比(OR)或危险比(HR)及 95% 置信区间(CI)。我们分析了七项入选的临床试验,所有试验均为观察性研究。与单一疗法相比,联合疗法与较低的 28 天死亡率之间存在非显著的有利关联(HR 0.67 [0.43-1.05],OR 0.73 [0.45-1.18])。I2值分别为60%和72%,表明异质性很高。作为次要结果,两组的出血并发症相似(汇总 OR 1.11 [0.55-2.23],I2 值 55%)。虽然这项分析结果不能证实 AT 和 rTM 联合疗法对脓毒症 DIC 有统计学意义上的显著效果,但在改善死亡率方面却显示出良好的效果。出血发生率较低,临床上可行。要得出更确切的结果,还需要进一步研究。本研究已在大学医院医学信息网(UMIN)临床试验注册中心注册(UMIN ID:000049820)。
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引用次数: 0
Oxidative stress in acute pulmonary embolism: emerging roles and therapeutic implications. 急性肺栓塞中的氧化应激:新的作用和治疗意义。
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-01-12 DOI: 10.1186/s12959-023-00577-1
Jingchao Yang, Jinzhu Xu, Shuanglan Xu, Zeqin Fan, Chenshao Zhu, Jianyuan Wan, Jiao Yang, Xiqian Xing

Oxidative stress is an imbalance between the body's reactive oxygen species and antioxidant defense mechanisms. Oxidative stress is involved in the development of several cardiovascular diseases, such as pulmonary hypertension, atherosclerosis, and diabetes mellitus. A growing number of studies have suggested the potential role of oxidative stress in the pathogenesis of pulmonary embolism. Biomarkers of oxidative stress in pulmonary embolism have also been explored, such as matrix metalloproteinases, asymmetric dimethylarginine, and neutrophil/lymphocyte ratio. Here, we comprehensively summarize some oxidative stress mechanisms and biomarkers in the development of acute pulmonary embolism and summarize related treatments based on antioxidant stress to explore effective treatment strategies for acute pulmonary embolism.

氧化应激是体内活性氧与抗氧化防御机制之间的失衡。氧化应激与肺动脉高压、动脉粥样硬化和糖尿病等多种心血管疾病的发病有关。越来越多的研究表明,氧化应激在肺栓塞的发病机制中可能发挥作用。人们还探索了肺栓塞中氧化应激的生物标志物,如基质金属蛋白酶、不对称二甲基精氨酸和中性粒细胞/淋巴细胞比率。在此,我们全面总结了急性肺栓塞发病过程中的一些氧化应激机制和生物标志物,并总结了基于抗氧化应激的相关治疗方法,以探讨急性肺栓塞的有效治疗策略。
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引用次数: 0
Progress in the clinical effects and adverse reactions of ticagrelor 替卡格雷的临床效果和不良反应研究进展
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-01-10 DOI: 10.1186/s12959-023-00559-3
Peng Wei, Xiaoqing Wang, Qiang Fu, Bangming Cao
Ticagrelor is a novel receptor antagonist that selectively binds to the P2Y12 receptor, thereby inhibiting adenosine diphosphate (ADP)-mediated platelet aggregation. Compared to clopidogrel, ticagrelor has the advantages of a fast onset, potent effects, and a reversible platelet inhibition function, which make this drug clinically suitable for treating acute coronary syndrome (ACS), especially acute ST-segment elevation myocardial infarction (STEMI). This review was performed to determine the basic characteristics, clinical effects, and adverse reactions of ticagrelor. Relevant trials and reports were obtained from the MEDLINE, Embase, and Cochrane Library databases. Ticagrelor is rapidly absorbed by the body after oral administration, exhibits inherent activity without requiring metabolic activation, and binds reversibly to the P2Y12 receptor. Ticagrelor has been recommended in ACS treatment guidelines worldwide due to its advantageous pharmacological properties and significant clinical benefits. Ticagrelor inhibits platelet aggregation, inhibits inflammatory response, enhances adenosine function, and has cardioprotective effects. However, ticagrelor also causes adverse reactions such as bleeding tendency, dyspnea, ventricular pause, gout, kidney damage, and thrombotic thrombocytopenic purpura in clinical treatment. Therefore, it is necessary to pay attention to risk assessments when using ticagrelor. Ticagrelor is a promising drug for the effective treatment of ACS. When using ticagrelor, individualized treatment should be provided based on the specific conditions of the patients to avoid serious adverse events.
替卡格雷是一种新型受体拮抗剂,可选择性地与P2Y12受体结合,从而抑制二磷酸腺苷(ADP)介导的血小板聚集。与氯吡格雷相比,替卡格雷具有起效快、作用强、血小板抑制功能可逆等优点,因此在临床上适用于治疗急性冠脉综合征(ACS),尤其是急性ST段抬高型心肌梗死(STEMI)。本综述旨在了解替卡格雷的基本特征、临床效果和不良反应。相关试验和报告来自 MEDLINE、Embase 和 Cochrane Library 数据库。替卡格雷口服后可迅速被人体吸收,无需代谢激活即可显示出固有活性,并可逆性地与 P2Y12 受体结合。由于其优越的药理特性和显著的临床疗效,全世界的 ACS 治疗指南都推荐使用替卡格雷。替卡格雷可抑制血小板聚集,抑制炎症反应,增强腺苷功能,并具有保护心脏的作用。但在临床治疗中,替卡格雷也会引起出血倾向、呼吸困难、心室停搏、痛风、肾损害、血栓性血小板减少性紫癜等不良反应。因此,在使用替卡格雷时必须注意风险评估。替卡格雷是一种有望有效治疗 ACS 的药物。在使用替卡格雷时,应根据患者的具体情况进行个体化治疗,以避免严重不良事件的发生。
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引用次数: 0
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Thrombosis Journal
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