In the current literature, the utility of transient ischemic attack (TIA) diagnosis is under revision by the scientific community and experts. If initially this term was considered a valid diagnostic category, over the years the definition of TIA has been completely subverted, underlining the scientific lability of this nosological entity [...]
{"title":"Is transient ischemic attack a minor stroke?","authors":"Ettore Dolcetti, Antonio Bruno, D. Centonze","doi":"10.4081/btvb.2022.31","DOIUrl":"https://doi.org/10.4081/btvb.2022.31","url":null,"abstract":"In the current literature, the utility of transient ischemic attack (TIA) diagnosis is under revision by the scientific community and experts. If initially this term was considered a valid diagnostic category, over the years the definition of TIA has been completely subverted, underlining the scientific lability of this nosological entity [...]","PeriodicalId":186928,"journal":{"name":"Bleeding, Thrombosis, and Vascular Biology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129255995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
For many years, the brain was considered as a closed system protected by the blood-brain barrier (BBB), where only the hormones produced by the body can mediate the interplay between the brain and the blood. Indeed, hormones, crossing the BBB and binding to specific receptors on the brain cells, regulates neuronal and synaptic plasticity and neurogenesis [...].
{"title":"Are platelets more than a model of brain neurons?","authors":"I. Canobbio, S. Barbieri","doi":"10.4081/btvb.2022.29","DOIUrl":"https://doi.org/10.4081/btvb.2022.29","url":null,"abstract":"For many years, the brain was considered as a closed system protected by the blood-brain barrier (BBB), where only the hormones produced by the body can mediate the interplay between the brain and the blood. Indeed, hormones, crossing the BBB and binding to specific receptors on the brain cells, regulates neuronal and synaptic plasticity and neurogenesis [...].","PeriodicalId":186928,"journal":{"name":"Bleeding, Thrombosis, and Vascular Biology","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134442564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Lancellotti, M. Sacco, M. Tardugno, A. Ferretti, R. De Cristofaro
Von Willebrand factor (VWF), a blood multimeric protein with a very high molecular weight, plays a crucial role in the primary hemostasis, the physiological process characterized by the adhesion of blood platelets to the injured vessel wall. Hydrodynamic forces are responsible for the VWF multimers conformational transitions from a globular to a stretched linear conformation. These characteristics render this protein a valuable object to be investigated by mechanochemistry, the biophysical chemistry branch that studies the effects of shear forces on protein conformation. This review will focus on the structural elements of the VWF molecule involved in the biochemical response to shear forces. The stretched VWF conformation favors the interaction with the platelet GpIb and at the same time with ADAMTS-13, the zinc-protease that cleaves VWF in the A2 domain, limiting its prothrombotic capacity. It is important to consider the level or the function of VWF or ADAMTS-13 always in relation each other, keeping in mind that in many thrombotic forms of microangiopathies the reduction of the ratio between the ADAMTS-13 activity and the VWF level (lower than 0.5) can be a valuable parameter to predict a real thrombotic risk. Hence, a significant increase in VWF level alone, even without any reduction of ADAMTS-13 concentration, would still be responsible for a significant reduction of the ADAMTS-13/VWF ratio, which ultimately could reflect or predict a prothrombotic risk. Future studies will have to validate the concept whether ADAMTS-13/VWF ratio could a valuable and reliable biomarker to predict or confirm the presence of thrombotic risk in several morbid conditions.
{"title":"The Von Willebrand factor-ADAMTS-13 axis: a two-faced Janus in bleeding and thrombosis","authors":"S. Lancellotti, M. Sacco, M. Tardugno, A. Ferretti, R. De Cristofaro","doi":"10.4081/btvb.2022.11","DOIUrl":"https://doi.org/10.4081/btvb.2022.11","url":null,"abstract":"Von Willebrand factor (VWF), a blood multimeric protein with a very high molecular weight, plays a crucial role in the primary hemostasis, the physiological process characterized by the adhesion of blood platelets to the injured vessel wall. Hydrodynamic forces are responsible for the VWF multimers conformational transitions from a globular to a stretched linear conformation. These characteristics render this protein a valuable object to be investigated by mechanochemistry, the biophysical chemistry branch that studies the effects of shear forces on protein conformation. This review will focus on the structural elements of the VWF molecule involved in the biochemical response to shear forces. The stretched VWF conformation favors the interaction with the platelet GpIb and at the same time with ADAMTS-13, the zinc-protease that cleaves VWF in the A2 domain, limiting its prothrombotic capacity. It is important to consider the level or the function of VWF or ADAMTS-13 always in relation each other, keeping in mind that in many thrombotic forms of microangiopathies the reduction of the ratio between the ADAMTS-13 activity and the VWF level (lower than 0.5) can be a valuable parameter to predict a real thrombotic risk. Hence, a significant increase in VWF level alone, even without any reduction of ADAMTS-13 concentration, would still be responsible for a significant reduction of the ADAMTS-13/VWF ratio, which ultimately could reflect or predict a prothrombotic risk. Future studies will have to validate the concept whether ADAMTS-13/VWF ratio could a valuable and reliable biomarker to predict or confirm the presence of thrombotic risk in several morbid conditions.","PeriodicalId":186928,"journal":{"name":"Bleeding, Thrombosis, and Vascular Biology","volume":"74 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122199572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The phase 3 clinical study of gene transfer in hemophilia A using the BioMarin vector AAV5-hFVIII-SQ (also identified as valoctocogene roxaparvovec) recently reported the results obtained in as many as 134 adult men with severe hemophilia A, so that it is at the moment the largest gene transfer study ever conducted in a rare monogenic disorder [...].
{"title":"Gene transfer in hemophilia A: not cogent yet","authors":"P. Mannucci","doi":"10.4081/btvb.2022.32","DOIUrl":"https://doi.org/10.4081/btvb.2022.32","url":null,"abstract":"The phase 3 clinical study of gene transfer in hemophilia A using the BioMarin vector AAV5-hFVIII-SQ (also identified as valoctocogene roxaparvovec) recently reported the results obtained in as many as 134 adult men with severe hemophilia A, so that it is at the moment the largest gene transfer study ever conducted in a rare monogenic disorder [...].","PeriodicalId":186928,"journal":{"name":"Bleeding, Thrombosis, and Vascular Biology","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133763145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. De Girolamo, L. Sarti, Sonia Cecoli, K. Bonora, C. Ajolfi, F. Bellelli, V. Coluccio, G. Palareti, M. Marietta
This is a retrospective, record-linkage study aimed at comparing the effectiveness and safety of two management models of vitamin K antagonists: a Network model (NAS), in which anticoagulation clinics and general practitioners (GP) share the same management software and database, and an individual General Practitioners model. Main outcomes were thromboembolic events (TE), major bleeding (MB) and all-cause mortality. Crude incidence rate and sub-distribution hazard ratio were calculated. Fine and Grey models were used to calculate SHR in multi-variable analysis. 9,418 patients in the NAS and 5,508 in the Routine General Care (RGC) cohort were included. Patients in the NAS cohort had a lower incidence of TE and mortality in respect to the RGC (sHR 0.76%, 95% CI 0.64-0.90 and 0.82%, 95% CI 0.75-0.89, respectively). More patients in the NAS than in the RGC cohort attained a Time in Therapeutic Range >60% (62.2% vs 35.7%, p<0.001). No statistically significant difference was found in MB incidence. This study shows that the NAS model for vitamin K antagonist oral anticoagulants management significantly improves the TTR and reduces the incidence of TE and mortality, without affecting the MB rate.
这是一项回顾性的记录链接研究，旨在比较两种维生素K拮抗剂管理模式的有效性和安全性:一种是网络模式(NAS)，其中抗凝诊所和全科医生(GP)共享相同的管理软件和数据库，另一种是个体全科医生模式。主要结局为血栓栓塞事件(TE)、大出血(MB)和全因死亡率。计算粗发病率和亚分布风险比。在多变量分析中，采用精细模型和灰色模型计算SHR。纳入了9418名NAS队列患者和5508名常规普通护理(RGC)队列患者。与RGC组相比，NAS组患者TE发病率和死亡率较低(sHR分别为0.76%，95% CI 0.64-0.90和0.82%，95% CI 0.75-0.89)。NAS组比RGC组有更多的患者达到治疗范围内的时间为60% (62.2% vs 35.7%， p<0.001)。两组间MB发病率无统计学差异。本研究表明，NAS模型对维生素K拮抗剂口服抗凝剂管理可显著改善TTR，降低TE发生率和死亡率，而不影响MB率。
{"title":"Safety and efficacy of treatment with vitamin K antagonists in patients managed in a network of anticoagulation services or as routine general care","authors":"G. De Girolamo, L. Sarti, Sonia Cecoli, K. Bonora, C. Ajolfi, F. Bellelli, V. Coluccio, G. Palareti, M. Marietta","doi":"10.4081/btvb.2022.9","DOIUrl":"https://doi.org/10.4081/btvb.2022.9","url":null,"abstract":"This is a retrospective, record-linkage study aimed at comparing the effectiveness and safety of two management models of vitamin K antagonists: a Network model (NAS), in which anticoagulation clinics and general practitioners (GP) share the same management software and database, and an individual General Practitioners model. Main outcomes were thromboembolic events (TE), major bleeding (MB) and all-cause mortality. Crude incidence rate and sub-distribution hazard ratio were calculated. Fine and Grey models were used to calculate SHR in multi-variable analysis. 9,418 patients in the NAS and 5,508 in the Routine General Care (RGC) cohort were included. Patients in the NAS cohort had a lower incidence of TE and mortality in respect to the RGC (sHR 0.76%, 95% CI 0.64-0.90 and 0.82%, 95% CI 0.75-0.89, respectively). More patients in the NAS than in the RGC cohort attained a Time in Therapeutic Range >60% (62.2% vs 35.7%, p<0.001). No statistically significant difference was found in MB incidence. This study shows that the NAS model for vitamin K antagonist oral anticoagulants management significantly improves the TTR and reduces the incidence of TE and mortality, without affecting the MB rate.","PeriodicalId":186928,"journal":{"name":"Bleeding, Thrombosis, and Vascular Biology","volume":"925 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133216508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
For almost 90 years, the discovery and development of anticoagulant drugs have focused on maximizing their antithrombotic efficacy while minimizing the risk of bleeding, in addition to providing manageable compounds with predictable and/or monitorable effects [...].
{"title":"Milvexian and other drugs targeting Factor XI: a new era of anticoagulation?","authors":"M. Donadini, W. Ageno","doi":"10.4081/btvb.2022.22","DOIUrl":"https://doi.org/10.4081/btvb.2022.22","url":null,"abstract":"For almost 90 years, the discovery and development of anticoagulant drugs have focused on maximizing their antithrombotic efficacy while minimizing the risk of bleeding, in addition to providing manageable compounds with predictable and/or monitorable effects [...].","PeriodicalId":186928,"journal":{"name":"Bleeding, Thrombosis, and Vascular Biology","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126081397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Scientific literature is overflowing of significance testing and p-values. P-value states how discordant the observed finding is with a null hypothesis. P<0.05 indicates that an association greater than that detected would happen less than 5% of the time under a null hypothesis of no association [...].
{"title":"Moving beyond p-value","authors":"A. Di Castelnuovo, L. Iacoviello","doi":"10.4081/btvb.2022.30","DOIUrl":"https://doi.org/10.4081/btvb.2022.30","url":null,"abstract":"Scientific literature is overflowing of significance testing and p-values. P-value states how discordant the observed finding is with a null hypothesis. P<0.05 indicates that an association greater than that detected would happen less than 5% of the time under a null hypothesis of no association [...].","PeriodicalId":186928,"journal":{"name":"Bleeding, Thrombosis, and Vascular Biology","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133722604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
While on conventional anticoagulation, up to 50% of patients with one or more episodes of proximal deep vein thrombosis (DVT) can develop post-thrombotic (PTS) manifestations. The potential strategies for PTS prevention are the treatment of acute DVT with catheter-directed thrombolysis (CDT), the use of elastic compression stockings (ECS) and that of the direct oral anticoagulants (DOAC) in place of vitamin K antagonists (VKA) for the initial and long-term treatment of DVT. Based on the results of three randomized clinical trials, CDT cannot be recommended on a routine basis because of its invasiveness, the associated risk of major bleedings and the uncertainty about its efficacy. According to the results of a placebo-controlled randomized clinical trial, ECS are no longer recommended for PTS prevention on a routine basis. However, based on the results of a recent subanalysis of a prospective cohort study, patients with residual vein thrombosis and/or popliteal valve reflux at three months are likely to benefit from ECS for at least six months. Finally, following the demonstration that the inadequacy of VKA therapy plays a key role in the PTS development, several retrospective and prospective studies have shown that the use of DOACs for the initial and long-term treatment of DVT in place of VKAs reduces the risk of PTS by approximately 50%. In conclusion, the availability of DOACs and the potential of ECS in selected patients with proximal DVT are expected to play a key role for decreasing the rate and the severity of PTS in the forthcoming years.
{"title":"New perspectives for prevention of the post-thrombotic syndrome","authors":"P. Prandoni","doi":"10.4081/btvb.2022.20","DOIUrl":"https://doi.org/10.4081/btvb.2022.20","url":null,"abstract":"While on conventional anticoagulation, up to 50% of patients with one or more episodes of proximal deep vein thrombosis (DVT) can develop post-thrombotic (PTS) manifestations. The potential strategies for PTS prevention are the treatment of acute DVT with catheter-directed thrombolysis (CDT), the use of elastic compression stockings (ECS) and that of the direct oral anticoagulants (DOAC) in place of vitamin K antagonists (VKA) for the initial and long-term treatment of DVT. Based on the results of three randomized clinical trials, CDT cannot be recommended on a routine basis because of its invasiveness, the associated risk of major bleedings and the uncertainty about its efficacy. According to the results of a placebo-controlled randomized clinical trial, ECS are no longer recommended for PTS prevention on a routine basis. However, based on the results of a recent subanalysis of a prospective cohort study, patients with residual vein thrombosis and/or popliteal valve reflux at three months are likely to benefit from ECS for at least six months. Finally, following the demonstration that the inadequacy of VKA therapy plays a key role in the PTS development, several retrospective and prospective studies have shown that the use of DOACs for the initial and long-term treatment of DVT in place of VKAs reduces the risk of PTS by approximately 50%. In conclusion, the availability of DOACs and the potential of ECS in selected patients with proximal DVT are expected to play a key role for decreasing the rate and the severity of PTS in the forthcoming years.","PeriodicalId":186928,"journal":{"name":"Bleeding, Thrombosis, and Vascular Biology","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117335141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. de Gaetano, C. Cerletti, L. Iacoviello, M. Donati
In the Sixties, the few anti-thrombotic drugs available were administered following several criteria including tradition of the “School”, preference of the doctor in charge, pressure of pharmaceutical companies [...]
{"title":"The night of randomized clinical trials where all patients are black: a need to estimate variability in treatment effects","authors":"G. de Gaetano, C. Cerletti, L. Iacoviello, M. Donati","doi":"10.4081/btvb.2022.24","DOIUrl":"https://doi.org/10.4081/btvb.2022.24","url":null,"abstract":"In the Sixties, the few anti-thrombotic drugs available were administered following several criteria including tradition of the “School”, preference of the doctor in charge, pressure of pharmaceutical companies [...]","PeriodicalId":186928,"journal":{"name":"Bleeding, Thrombosis, and Vascular Biology","volume":"69 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130041668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This narrative review article summarizes the strong available evidence that casually links indoor and outdoor air pollution to cardiovascular disease. It also discusses as a possible approach to mitigate this ubiquitous risk factor the use in the household of ornamental potted plants, and their variable degree of effectiveness for the removal of different indoor pollutants such as volatile organic compounds (formaldehyde, benzene, toluene, xylene). Thus, the choice of the plants should be tailored to the types and concentrations of the pollutants present in each household. Outdoor air is less polluted than indoor air in terms of concentrations of the gaseous (NO2) and particulate components (PM10, PM2.5, PM0.1), but it does hamper to a higher extent health because a large fraction of the population is inevitably exposed at the time of breezing. Being cognizant of the difficulties currently encountered in the attempts to mitigate the major sources of ambient air pollution (vehicle traffic and domestic heating) a strategy based upon a massive increase of green spaces in urban areas has been shown not only to positively mitigate air pollution but also improve life expectancy, general health and resilience.
{"title":"An ecological alliance against air pollution and cardiovascular disease","authors":"P. Mannucci","doi":"10.4081/btvb.2022.21","DOIUrl":"https://doi.org/10.4081/btvb.2022.21","url":null,"abstract":"This narrative review article summarizes the strong available evidence that casually links indoor and outdoor air pollution to cardiovascular disease. It also discusses as a possible approach to mitigate this ubiquitous risk factor the use in the household of ornamental potted plants, and their variable degree of effectiveness for the removal of different indoor pollutants such as volatile organic compounds (formaldehyde, benzene, toluene, xylene). Thus, the choice of the plants should be tailored to the types and concentrations of the pollutants present in each household. Outdoor air is less polluted than indoor air in terms of concentrations of the gaseous (NO2) and particulate components (PM10, PM2.5, PM0.1), but it does hamper to a higher extent health because a large fraction of the population is inevitably exposed at the time of breezing. Being cognizant of the difficulties currently encountered in the attempts to mitigate the major sources of ambient air pollution (vehicle traffic and domestic heating) a strategy based upon a massive increase of green spaces in urban areas has been shown not only to positively mitigate air pollution but also improve life expectancy, general health and resilience.","PeriodicalId":186928,"journal":{"name":"Bleeding, Thrombosis, and Vascular Biology","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123576096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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