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Implementation of early prophylaxis for deep-vein thrombosis in intracerebral hemorrhage patients: an observational study from the Chinese Stroke Center Alliance. 脑出血患者深静脉血栓早期预防的实施:来自中国卒中中心联盟的观察性研究。
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-02-28 DOI: 10.1186/s12959-024-00592-w
Ran Zhang, Weige Sun, Yana Xing, Yongjun Wang, Zixiao Li, Liping Liu, Hongqiu Gu, Kaixuan Yang, Xin Yang, Chunjuan Wang, Qingbo Liu, Qian Xiao, Weixin Cai

Background: There is substantial evidence to support the use of several methods for preventing deep-vein thrombosis (DVT) following intracerebral hemorrhage (ICH). However, the extent to which these measures are implemented in clinical practice and the factors influencing patients' receipt of preventive measures remain unclear. Therefore, we aimed to evaluate the rate of the early implementation of DVT prophylaxis and the factors associated with its success in patients with ICH.

Methods: This study enrolled 49,950 patients with spontaneous ICH from the Chinese Stroke Center Alliance (CSCA) between August 2015 and July 2019. Early DVT prophylaxis implementation was defined as an intervention occurring within 48 h after admission. Univariate and multivariate logistic regression analyses were conducted to identify the rate and factors associated with the implementation of early prophylaxis for DVT in patients with ICH.

Results: Among the 49,950 ICH patients, the rate of early DVT prophylaxis implementation was 49.9%, the rate of early mobilization implementation was 29.49%, and that of pharmacological prophylaxis was 2.02%. Factors associated with an increased likelihood of early DVT prophylaxis being administered in the multivariable model included receiving early rehabilitation therapy (odds ratio [OR], 2.531); admission to stroke unit (OR 2.231); admission to intensive care unit (OR 1.975); being located in central (OR 1.879) or eastern regions (OR 1.529); having a history of chronic obstructive pulmonary disease (OR 1.292), ischemic stroke (OR 1.245), coronary heart disease or myocardial infarction (OR 1.2); taking antihypertensive drugs (OR 1.136); and having a higher Glasgow Coma Scale (GCS) score (OR 1.045). Conversely, being male (OR 0.936), being hospitalized in tertiary hospitals (OR 0.778), and having a previous intracranial hemorrhage (OR 0.733) were associated with a lower likelihood of early DVT prophylaxis being administered in patients with ICH.

Conclusions: The implementation rate of early DVT prophylaxis among Chinese patients with ICH was subpar, with pharmacological prophylaxis showing the lowest prevalence. Various controllable factors exerted an impact on the implementation of early DVT prophylaxis in this population.

背景:有大量证据支持使用多种方法预防脑内出血(ICH)后深静脉血栓形成(DVT)。然而,这些措施在临床实践中的实施程度以及影响患者接受预防措施的因素仍不清楚。因此,我们旨在评估 ICH 患者早期实施深静脉血栓预防措施的比率及其成功的相关因素:本研究在2015年8月至2019年7月期间,从中国卒中中心联盟(CSCA)招募了49950名自发性ICH患者。早期深静脉血栓预防措施的实施被定义为入院后 48 小时内进行的干预。研究人员进行了单变量和多变量逻辑回归分析,以确定ICH患者实施深静脉血栓早期预防的比率和相关因素:在 49,950 名 ICH 患者中,早期预防深静脉血栓的实施率为 49.9%,早期动员的实施率为 29.49%,药物预防的实施率为 2.02%。在多变量模型中,与早期实施深静脉血栓预防可能性增加相关的因素包括:接受早期康复治疗(几率比 [OR],2.531);入住卒中单元(OR 2.231);入住重症监护单元(OR 1.975);位于中部地区(OR 1.879)或东部地区(OR 1.529);有慢性阻塞性肺病(OR 1.292)、缺血性中风(OR 1.245)、冠心病或心肌梗死(OR 1.2)病史;服用降压药(OR 1.136);格拉斯哥昏迷量表(GCS)评分较高(OR 1.045)。相反,男性(OR 0.936)、在三级医院住院(OR 0.778)和曾有过颅内出血(OR 0.733)与 ICH 患者接受早期深静脉血栓预防的可能性较低有关:结论:中国 ICH 患者早期预防深静脉血栓形成的实施率较低,其中药物预防的实施率最低。各种可控因素对该人群实施早期深静脉血栓预防措施产生了影响。
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引用次数: 0
Establishment and validation of a nomogram predicting the risk of deep vein thrombosis before total knee arthroplasty. 建立并验证预测全膝关节置换术前深静脉血栓风险的提名图。
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-02-16 DOI: 10.1186/s12959-024-00588-6
Zehua Wang, Xingjia Mao, Zijian Guo, Guoyu Che, Changxin Xiang, Chuan Xiang

Purpose: This study aimed to analyze the independent risk factors contributing to preoperative DVT in TKA and constructed a predictive nomogram to accurately evaluate its occurrence based on these factors.

Methods: The study encompassed 496 patients who underwent total knee arthroplasty at our hospital between June 2022 and June 2023. The dataset was randomly divided into a training set (n = 348) and a validation set (n = 148) in a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis were used to screen the predictors of preoperative DVT occurrence in TKA and construct a nomogram. The performance of the predictive models was evaluated using the concordance index (C-index), calibration curves, and the receiver operating characteristic (ROC) curves. Decision curve analysis was used to analyze the clinical applicability of nomogram.

Results: A total of 496 patients who underwent TKA were included in this study, of which 28 patients were examined for lower extremity DVT preoperatively. Platelet crit, Platelet distribution width, Procalcitonin, prothrombin time, and D-dimer were predictors of preoperative occurrence of lower extremity DVT in the nomograms of the TKA patients. In addition, the areas under the curve of the ROC of the training and validation sets were 0.935 (95%CI: 0.880-0.990) and 0.854 (95%CI: 0.697-1.000), and the C-indices of the two sets were 0.919 (95%CI: 0.860-0.978) and 0.900 (95%CI: 0.791-1.009). The nomogram demonstrated precise risk prediction of preoperative DVT occurrence in TKA as confirmed by the calibration curve and decision curve analysis.

Conclusions: This Nomogram demonstrates great differentiation, calibration and clinical validity. By assessing individual risk, clinicians can promptly detect the onset of DVT, facilitating additional life monitoring and necessary medical interventions to prevent the progression of DVT effectively.

目的:本研究旨在分析导致全膝关节置换术术前深静脉血栓形成的独立风险因素,并根据这些因素构建预测提名图,以准确评估其发生率:研究对象为2022年6月至2023年6月期间在我院接受全膝关节置换术的496例患者。数据集按 7:3 的比例随机分为训练集(n = 348)和验证集(n = 148)。使用最小绝对收缩和选择算子(LASSO)和多变量逻辑回归分析筛选 TKA 术前深静脉血栓发生的预测因素并构建提名图。使用一致性指数(C-index)、校准曲线和接收者操作特征曲线(ROC)对预测模型的性能进行了评估。决策曲线分析用于分析提名图的临床适用性:本研究共纳入了 496 例接受 TKA 的患者,其中 28 例患者在术前接受了下肢深静脉血栓检查。在 TKA 患者的提名图中,血小板临界值、血小板分布宽度、降钙素原、凝血酶原时间和 D-二聚体是术前发生下肢深静脉血栓的预测因子。此外,训练集和验证集的 ROC 曲线下面积分别为 0.935(95%CI:0.880-0.990)和 0.854(95%CI:0.697-1.000),两组的 C 指数分别为 0.919(95%CI:0.860-0.978)和 0.900(95%CI:0.791-1.009)。校准曲线和决策曲线分析证实,提名图能精确预测 TKA 术前深静脉血栓发生的风险:该提名图具有很高的区分度、校准性和临床有效性。通过评估个体风险,临床医生可以及时发现深静脉血栓的发生,便于进行额外的生命监测和必要的医疗干预,从而有效预防深静脉血栓的恶化。
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引用次数: 0
Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage. 不明原因复发性流产的巴勒斯坦妇女中遗传性血栓性疾病突变及其组合的关联。
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-02-13 DOI: 10.1186/s12959-024-00587-7
Ayman A Najjar, Imam Hassouna, Mahmoud A Srour, Hany M Ibrahim, Randa Y Assi, Heba M Abd El Latif

Background: Inherited thrombophilia (IT) has a complex pathophysiology and is associated with recurrent miscarriage (RM) by causing placental insufficiency and inhibiting fetal development. However, thrombophilia screening in unexplained RM cases is still questionable. This study aimed to investigate the association between the common eight IT mutations and their combinations among Palestinian women with unexplained RM.

Methods: This is an unmatched case-control study with 200 women (100 unexplained RM cases, 100 controls). Eight common IT mutations namely Factor V Leiden (FVL), prothrombin gene (FII) G202120A, Methylenetetrahydrofolate Reductase (MTHFR) gene (C677T and A1298C), B-fibrinogen gene - 455G > A, FV HR2 A4070G, Plasminogen activator inhibitor 1 (PAI1) 5G/4G and Factor XIIIA (FXIIIA) V34L; were analyzed. The first five mutations were analyzed by Restriction Fragment Length Polymorphism PCR and the other three mutations were analyzed using Amplification Refractory Mutation System PCR.

Results: The prevalence of the eight IT mutations among the control group was in the order PAI1 5G/4G (69%), MTHFR C677T (53%) and A1298C (47%), BFG - 455G > A (35%), FVL and FV HR2 (each 18%), FXIIIA V34L (16%) and FII G20210A (3%). Patients had a higher percentage of MTHFR A1298C (heterozygotes and mutant homozygote) compared to controls (p = 0.016). Frequencies of mutant alleles MTHFR A1298C (p < 0.001) and FXIIIA V34L (p = 0.009) were higher among patients compared to controls. No significant differences were observed for all other mutations or mutant alleles. Most patients (75%) and controls (75%) have 2-4 mutant alleles out of 8 mutant alleles studied, while 1% of patients and 2% of controls have zero mutant alleles. None of the combinations of the most often studied mutations (FVL, FII G20210A, MTHFR C1677T, and MTHFR A1298C) showed a significant difference between patients and controls.

Conclusions: There was a significant association between unexplained RM and the mutant alleles of MTHFR A1298C and FXIIIA V34L. No significant association was observed between unexplained RM and the combination of both mutant alleles for the mutations studied. This study is the first Palestinian report that evaluates eight inherited thrombophilia mutations and their alleles' combinations in unexplained RM cases.

背景:遗传性血栓性疾病(IT)具有复杂的病理生理学,并通过导致胎盘功能不全和抑制胎儿发育与复发性流产(RM)有关。然而,在不明原因的流产病例中进行血栓性疾病筛查仍是个问题。本研究旨在调查原因不明的巴勒斯坦妇女中常见的八种 IT 基因突变及其组合之间的关联:这是一项非匹配病例对照研究,共有 200 名妇女参加(100 名不明原因 RM 病例,100 名对照)。研究分析了八种常见的 IT 变异,即因子 V Leiden(FVL)、凝血酶原基因(FII)G202120A、亚甲基四氢叶酸还原酶(MTHFR)基因(C677T 和 A1298C)、B-纤维蛋白原基因 - 455G > A、FV HR2 A4070G、凝血酶原激活物抑制剂 1(PAI1)5G/4G 和因子 XIIIA(FXIIIA)V34L。前五种突变通过限制性片段长度多态性聚合酶链反应(RCR)进行分析,其他三种突变通过扩增难辨突变系统聚合酶链反应(PCR)进行分析:结果:在对照组中,八种 IT 变异的发生率依次为 PAI1 5G/4G (69%)、MTHFR C677T (53%) 和 A1298C (47%)、BFG - 455G > A (35%)、FVL 和 FV HR2 (各 18%)、FXIIIA V34L (16%) 和 FII G20210A (3%)。与对照组相比,患者的 MTHFR A1298C(杂合子和突变等位基因)比例更高(p = 0.016)。突变等位基因 MTHFR A1298C 的频率(p 结论:MTHFR A1298C 的突变等位基因的频率与对照组相比更高(p = 0.016):原因不明的 RM 与 MTHFR A1298C 和 FXIIIA V34L 的突变等位基因之间存在明显关联。在所研究的突变中,没有观察到不明原因的 RM 与两个突变等位基因的组合有明显关联。这项研究是巴勒斯坦的第一份报告,评估了不明原因 RM 病例中的 8 种遗传性血栓性疾病突变及其等位基因组合。
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引用次数: 0
SERPINC1 c.1247dupC: a novel SERPINC1 gene mutation associated with familial thrombosis results in a secretion defect and quantitative antithrombin deficiency. SERPINC1 c.1247dupC:与家族性血栓症相关的新型 SERPINC1 基因突变导致分泌缺陷和定量抗凝血酶缺乏症。
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-02-12 DOI: 10.1186/s12959-024-00589-5
Maximilian Ruf, Sarah Cunningham, Alexandra Wandersee, Regine Brox, Susanne Achenbach, Julian Strobel, Holger Hackstein, Sabine Schneider

Background: Antithrombin (AT) is an important anticoagulant in hemostasis. We describe here the characterization of a novel AT mutation associated with clinically relevant thrombosis. A pair of sisters with confirmed type I AT protein deficiency was genetically analyzed on suspicion of an inherited SERPINC1 mutation. A frameshift mutation, c.1247dupC, was identified and the effect of this mutation was examined on the cellular and molecular level.

Methods: Plasmids for the expression of wild-type (WT) and mutated SERPINC1 coding sequence (CDS) fused to green fluorescent protein (GFP) or hemagglutinin (HA) tag were transfected into HEK293T cells. Subcellular localization and secretion of the respective fusion proteins were analyzed by confocal laser scanning microscopy and Western blot.

Results: The c.1247dupC mutation results in a frameshift in the CDS of the SERPINC1 gene and a subsequently altered amino acid sequence (p.Ser417LysfsTer48). This alteration affects the C-terminus of the AT antigen and results in impaired secretion as confirmed by GFP- and HA-tagged mutant AT analyzed in HEK293T cells.

Conclusion: The p.Ser417LysfsTer48 mutation leads to impaired secretion, thus resulting in a quantitative AT deficiency. This is in line with the type I AT deficiency observed in the patients.

背景:抗凝血酶(AT)是止血过程中一种重要的抗凝剂。我们在此描述了一种与临床相关血栓形成有关的新型 AT 基因突变的特征。一对姐妹被确诊为 I 型 AT 蛋白缺乏症,由于怀疑她们存在遗传性 SERPINC1 基因突变,我们对她们进行了基因分析。结果发现了一个框架移位突变(c.1247dupC),并对该突变在细胞和分子水平上的影响进行了研究:方法:将表达野生型(WT)和突变型 SERPINC1 编码序列(CDS)融合绿色荧光蛋白(GFP)或血凝素(HA)标签的质粒转染到 HEK293T 细胞中。通过激光共聚焦扫描显微镜和 Western 印迹分析了各自融合蛋白的亚细胞定位和分泌情况:结果:c.1247dupC 突变导致 SERPINC1 基因 CDS 框移位,氨基酸序列随之改变(p.Ser417LysfsTer48)。这种改变影响了 AT 抗原的 C-末端,并导致分泌受损,这一点已在 HEK293T 细胞中分析的 GFP 和 HA 标记的突变 AT 中得到证实:结论:p.Ser417LysfsTer48 突变导致分泌受损,从而导致定量 AT 缺乏。结论:p.Ser417LysfsTer48 突变导致分泌受损,从而导致定量 AT 缺乏症,这与在患者身上观察到的 I 型 AT 缺乏症相符。
{"title":"SERPINC1 c.1247dupC: a novel SERPINC1 gene mutation associated with familial thrombosis results in a secretion defect and quantitative antithrombin deficiency.","authors":"Maximilian Ruf, Sarah Cunningham, Alexandra Wandersee, Regine Brox, Susanne Achenbach, Julian Strobel, Holger Hackstein, Sabine Schneider","doi":"10.1186/s12959-024-00589-5","DOIUrl":"10.1186/s12959-024-00589-5","url":null,"abstract":"<p><strong>Background: </strong>Antithrombin (AT) is an important anticoagulant in hemostasis. We describe here the characterization of a novel AT mutation associated with clinically relevant thrombosis. A pair of sisters with confirmed type I AT protein deficiency was genetically analyzed on suspicion of an inherited SERPINC1 mutation. A frameshift mutation, c.1247dupC, was identified and the effect of this mutation was examined on the cellular and molecular level.</p><p><strong>Methods: </strong>Plasmids for the expression of wild-type (WT) and mutated SERPINC1 coding sequence (CDS) fused to green fluorescent protein (GFP) or hemagglutinin (HA) tag were transfected into HEK293T cells. Subcellular localization and secretion of the respective fusion proteins were analyzed by confocal laser scanning microscopy and Western blot.</p><p><strong>Results: </strong>The c.1247dupC mutation results in a frameshift in the CDS of the SERPINC1 gene and a subsequently altered amino acid sequence (p.Ser417LysfsTer48). This alteration affects the C-terminus of the AT antigen and results in impaired secretion as confirmed by GFP- and HA-tagged mutant AT analyzed in HEK293T cells.</p><p><strong>Conclusion: </strong>The p.Ser417LysfsTer48 mutation leads to impaired secretion, thus resulting in a quantitative AT deficiency. This is in line with the type I AT deficiency observed in the patients.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724052","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
Thrombosis-related characteristics of pregnant women with antithrombin deficiency, protein C deficiency and protein S deficiency in Japan. 日本抗凝血酶缺乏症、蛋白 C 缺乏症和蛋白 S 缺乏症孕妇的血栓相关特征。
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2024-02-08 DOI: 10.1186/s12959-024-00581-z
Takao Kobayashi, Kazuko Sugiura, Toshiyuki Ojima, Mariko Serizawa, Kyuya Hirai, Eriko Morishita

Background:  We previously conducted a primary survey of pregnant women with hereditary thrombophilia based on national surveillance in Japan, but did not examine their thrombosis-related characteristics. Antithrombin (AT) deficiency, protein C (PC) deficiency and protein S (PS) deficiency are the major types of hereditary thrombophilia in Japan.

Methods: We examined their detailed information related to thrombosis, and evaluated peripartum outcomes in comparison with control data obtained from the Japan Society of Obstetrics and Gynecology.

Results: Definite or probable AT deficiency, PC deficiency and PS deficiency were observed in 80, 50, and 317 pregnancies, respectively, from 2014 to 2018 in Japan, with prevalence rates among total deliveries of 0.011%, 0.007%, 0.044%. The number of pregnancies with AT, PC and PS deficiency might have been as many as 27, 17 and 108 every year if complete answers had been provided. In the peripartum period of current pregnancies, 27.5% of women with AT deficiency, 28.0% with PC deficiency and 13.2% with PS deficiency developed thrombosis (p < 0.001 vs. control). Pregnant women with AT and PC deficiency were more susceptible to thrombosis than those with PS deficiency (P < 0.01). Of the thromboses, 92.3% occurred during pregnancy, 62.8% at less than 15 gestational weeks. The earliest onset of thrombosis was 5 gestational weeks. Prophylactic anticoagulation significantly prevented the onset of both antepartum and postpartum thrombosis (p < 0.0001). The rate of recurrent pregnancy loss in women with low PC or PS activities was significantly higher than in controls (p < 0.0001); however, it is unknown whether recurrent pregnancy loss is related to hereditary PS deficiency. There seem to have been few serious maternal or fetal/neonatal complications due to placental insufficiency related to a hypercoagulable state other than growth restriction.

Conclusions: This survey revealed the thrombosis-related characteristics of pregnant women with hereditary thrombophilia in Japan. We suggest prophylactic anticoagulation to prevent maternal or fetal/neonatal complications.

背景: 我们曾在日本全国监测的基础上对患有遗传性血栓性疾病的孕妇进行了一次初步调查,但没有研究她们与血栓形成相关的特征。抗凝血酶(AT)缺乏症、蛋白 C(PC)缺乏症和蛋白 S(PS)缺乏症是日本遗传性血栓性疾病的主要类型:我们研究了他们与血栓形成相关的详细资料,并与日本妇产科学会的对照数据进行比较,评估了围产期的结果:2014年至2018年,在日本分别有80名、50名和317名孕妇观察到明确或可能的AT缺乏、PC缺乏和PS缺乏,在总分娩量中的患病率分别为0.011%、0.007%和0.044%。如果能提供完整的答案,每年缺乏AT、PC和PS的孕妇数量可能多达27例、17例和108例。在当前妊娠的围产期,27.5%的 AT 缺乏症妇女、28.0%的 PC 缺乏症妇女和 13.2%的 PS 缺乏症妇女出现了血栓形成(p 结论):这项调查揭示了日本遗传性血栓性疾病孕妇血栓形成的相关特征。我们建议进行预防性抗凝治疗,以预防母体或胎儿/新生儿并发症。
{"title":"Thrombosis-related characteristics of pregnant women with antithrombin deficiency, protein C deficiency and protein S deficiency in Japan.","authors":"Takao Kobayashi, Kazuko Sugiura, Toshiyuki Ojima, Mariko Serizawa, Kyuya Hirai, Eriko Morishita","doi":"10.1186/s12959-024-00581-z","DOIUrl":"10.1186/s12959-024-00581-z","url":null,"abstract":"<p><strong>Background: </strong> We previously conducted a primary survey of pregnant women with hereditary thrombophilia based on national surveillance in Japan, but did not examine their thrombosis-related characteristics. Antithrombin (AT) deficiency, protein C (PC) deficiency and protein S (PS) deficiency are the major types of hereditary thrombophilia in Japan.</p><p><strong>Methods: </strong>We examined their detailed information related to thrombosis, and evaluated peripartum outcomes in comparison with control data obtained from the Japan Society of Obstetrics and Gynecology.</p><p><strong>Results: </strong>Definite or probable AT deficiency, PC deficiency and PS deficiency were observed in 80, 50, and 317 pregnancies, respectively, from 2014 to 2018 in Japan, with prevalence rates among total deliveries of 0.011%, 0.007%, 0.044%. The number of pregnancies with AT, PC and PS deficiency might have been as many as 27, 17 and 108 every year if complete answers had been provided. In the peripartum period of current pregnancies, 27.5% of women with AT deficiency, 28.0% with PC deficiency and 13.2% with PS deficiency developed thrombosis (p < 0.001 vs. control). Pregnant women with AT and PC deficiency were more susceptible to thrombosis than those with PS deficiency (P < 0.01). Of the thromboses, 92.3% occurred during pregnancy, 62.8% at less than 15 gestational weeks. The earliest onset of thrombosis was 5 gestational weeks. Prophylactic anticoagulation significantly prevented the onset of both antepartum and postpartum thrombosis (p < 0.0001). The rate of recurrent pregnancy loss in women with low PC or PS activities was significantly higher than in controls (p < 0.0001); however, it is unknown whether recurrent pregnancy loss is related to hereditary PS deficiency. There seem to have been few serious maternal or fetal/neonatal complications due to placental insufficiency related to a hypercoagulable state other than growth restriction.</p><p><strong>Conclusions: </strong>This survey revealed the thrombosis-related characteristics of pregnant women with hereditary thrombophilia in Japan. We suggest prophylactic anticoagulation to prevent maternal or fetal/neonatal complications.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707944","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
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。
{"title":"Efficacy and safety of anticoagulant for treatment and prophylaxis of VTE patients with renal insufficiency: a systemic review and meta-analysis","authors":"Shuangshuang Ma, Guohui Fan, Feiya Xu, Xiaomeng Zhang, Yinong Chen, Yuzhi Tao, Yishan Li, Yanshuang Lyu, Peiran Yang, Dingyi Wang, Zhenguo Zhai, Chen Wang","doi":"10.1186/s12959-023-00576-2","DOIUrl":"https://doi.org/10.1186/s12959-023-00576-2","url":null,"abstract":"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.","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690412","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
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 3.1 4区 医学 Q2 Medicine 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。
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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。
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引用次数: 0
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Thrombosis Journal
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