Pub Date : 2024-02-28DOI: 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。
{"title":"Implementation of early prophylaxis for deep-vein thrombosis in intracerebral hemorrhage patients: an observational study from the Chinese Stroke Center Alliance.","authors":"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","doi":"10.1186/s12959-024-00592-w","DOIUrl":"10.1186/s12959-024-00592-w","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991266","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}
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.
{"title":"Establishment and validation of a nomogram predicting the risk of deep vein thrombosis before total knee arthroplasty.","authors":"Zehua Wang, Xingjia Mao, Zijian Guo, Guoyu Che, Changxin Xiang, Chuan Xiang","doi":"10.1186/s12959-024-00588-6","DOIUrl":"10.1186/s12959-024-00588-6","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10873976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747446","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}
Pub Date : 2024-02-13DOI: 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.
{"title":"Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage.","authors":"Ayman A Najjar, Imam Hassouna, Mahmoud A Srour, Hany M Ibrahim, Randa Y Assi, Heba M Abd El Latif","doi":"10.1186/s12959-024-00587-7","DOIUrl":"10.1186/s12959-024-00587-7","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730536","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}
Pub Date : 2024-02-12DOI: 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}
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}
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}
Pub Date : 2024-02-01DOI: 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.
{"title":"Causes of death after first time venous thromboembolism","authors":"Frida Lonnberg, Andreas Roos, Maria Farm, André Heurlin, Mantas Okas, Bruna Gigante, Anwar J Siddiqui","doi":"10.1186/s12959-024-00586-8","DOIUrl":"https://doi.org/10.1186/s12959-024-00586-8","url":null,"abstract":"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.","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139659377","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}
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.
{"title":"Nomogram for hospital-acquired venous thromboembolism among patients with cardiovascular diseases","authors":"Qin Luo, Xin Li, Zhihui Zhao, Qing Zhao, Zhihong Liu, Weixian Yang","doi":"10.1186/s12959-024-00584-w","DOIUrl":"https://doi.org/10.1186/s12959-024-00584-w","url":null,"abstract":"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.","PeriodicalId":22982,"journal":{"name":"Thrombosis Journal","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139589670","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}
Pub Date : 2024-01-23DOI: 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":3.1,"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}
Pub Date : 2024-01-17DOI: 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.
{"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}