Rare Variants in the ADAMTS13 Von Willebrand Factor-Binding Domain Contribute to Pediatric Stroke Original Articles

Background— Recently, we reported a gene network of ADAMTS (A Disintegrin-like and Metalloprotease with Thrombospondin motifs) genes as central component of the genetic risk contributing to pediatric stroke. ADAMTS13 is a prime example for such a key component as it cleaves von Willebrand factor multimers, reduces platelet adhesion and aggregation, and downregulates thrombus formation and inflammation. Methods and Results— We characterized the genetic architecture of ADAMTS13 through targeted next-generation sequencing of 48 affected children and their unaffected siblings and identified in total 241 variants (single nucleotide polymorphisms or insertions/deletions) in the ADAMTS13 gene. From these, based on significance in the sibship disequilibrium test (P
Source: Circulation: Cardiovascular Genetics - Category: Cardiology Authors: Tags: Cardiovascular Disease, Genetic, Association Studies, Ischemic Stroke, Thrombosis Original Articles Source Type: research

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AbstractThe interplay between thrombosis and inflammation, termed thrombo-inflammation, causes acute organ damage in diseases such as ischaemic stroke and venous thrombosis. We have recently identified tetraspanin Tspan18 as a novel regulator of thrombo-inflammation. The tetraspanins are a family of 33 membrane proteins in humans that regulate the trafficking, clustering, and membrane diffusion of specific partner proteins. Tspan18 partners with the store-operated Ca2+ entry channel Orai1 on endothelial cells. Orai1 appears to be expressed in all cells and is critical in health and disease. Orai1 mutations cause human immu...
Source: Medical Microbiology and Immunology - Category: Microbiology Source Type: research
CONCLUSION: Clots in diabetic patients had more fibrin and fewer erythrocyte components compared with patients without diabetes mellitus, while hyperglycemia on admission did not show association with clot composition. Further studies are needed to confirm these results. PMID: 31924102 [PubMed - as supplied by publisher]
Source: Interventional Neuroradiology - Category: Radiology Tags: Interv Neuroradiol Source Type: research
von Willebrand factor (VWF) and platelets are key mediators of normal hemostasis. At sites of vascular injury, VWF recruits platelets via binding to the platelet receptor glycoprotein Ibα (GPIbα). Over the past decades, it has become clear that many hemostatic factors, including VWF and platelets, are also involved in inflammatory processes, forming intriguing links between hemostasis, thrombosis, and inflammation. The so-called “thrombo-inflammatory” nature of the VWF-platelet axis becomes increasingly recognized in different cardiovascular pathologies, making it a potential therapeutic target to i...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Authors: Leebeek FWG, Muslem R Abstract Chronic heart failure (HF) is a growing health problem, and it is associated with high morbidity and mortality. Left ventricular assist devices (LVADs) are nowadays an important treatment option for patients with end-stage HF not only as a bridging tool to heart transplantation but also, as a permanent therapy for end-stage HF (destination therapy). The use of LVAD is associated with a high risk for bleeding complications and thromboembolic events, including pump thrombosis and ischemic stroke. Bleeding is the most frequent complication, occurring in 30% to 60% of patients, b...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Ischemic stroke is among the leading causes of disability and death worldwide. In acute ischemic stroke, the rapid recanalization of occluded cranial vessels is the primary therapeutic aim. However, experimental data (obtained using mostly the transient middle cerebral artery occlusion model) indicates that progressive stroke can still develop despite successful recanalization, a process termed “reperfusion injury.” Mounting experimental evidence suggests that platelets and T cells contribute to cerebral ischemia/reperfusion injury, and ischemic stroke is increasingly considered a thrombo-inflammatory disease. ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Publication date: Available online 8 August 2019Source: Canadian Journal of CardiologyAuthor(s): Leszek Drabik, Małgorzata Konieczyńska, Anetta UndasAbstractBackgroundFormation of dense fibrin clots has been reported in both atrial fibrillation (AF) and ischemic stroke. We have previously demonstrated that such clot properties can predict thromboembolism and major bleeding in AF patients treated with vitamin K antagonists (VKA). In this longitudinal cohort study, we evaluated whether impaired fibrinolysis is associated with clinical outcomes in AF.MethodsIn 236 patients with AF receiving with vitamin K antagonists (VKA),...
Source: Canadian Journal of Cardiology - Category: Cardiology Source Type: research
Thrombosis is the main pathogenesis of acute ischemic stroke (AIS). The main treatments for stroke either have limited efficacy or increase the risk of bleeding. ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is a metal protease that can effectively break down VWF (Von Willebrand Factor, VWF), the key factor in thrombus formation. Previous studies have proven that the abnormality of its activity is associated with many diseases. In recent years, it has been found that ADAMTS13 is closely related to stroke. We focus on the relationship between ADAMTS13 and acute ischemic stroke,...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
er SF Abstract Ischemic stroke is caused by a thromboembolic occlusion of cerebral arteries. Treatment is focused on fast and efficient removal of the occluding thrombus, either via intravenous thrombolysis or via endovascular thrombectomy. Recanalization, however, is not always successful and factors contributing to failure are not completely understood. Although the occluding thrombus is the primary target of acute treatment, little is known about its internal organization and composition. The aim of this study, therefore, was to better understand the internal organization of ischemic stroke thrombi on a molecul...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Von Willebrand Factor (VWF), ADAMTS13, fibrinogen and fibrinogen γ’ are associated with an increased risk of ischemic stroke. Carotid atherosclerosis is an important risk factor for ischemic stroke. Characteristics of the vulnerable plaque; intraplaque hemorrhage (IPH), plaque ulceration and lipid-rich necrotic core (LRNC) can be visualized with imaging techni ques. Since atherosclerosis might attribute to the association between coagulation factors and ischemic stroke risk, the aim of this study is to investigate the association between coagulation factors and atherosclerotic plaque characteristics in more detail.
Source: Thrombosis Research - Category: Hematology Authors: Tags: Full Length Article Source Type: research
Authors: Kreuziger LB, Massicotte MP Abstract Mechanical circulatory support (MCS) is the overarching term that encompasses the temporary and durable devices used in patients with severe heart failure. MCS disturbs the hematologic and coagulation system, leading to platelet activation, activation of the contact pathway of coagulation, and acquired von Willebrand syndrome. Ischemic stroke and major hemorrhage occur in up to 30% of patients. Hematologists are an essential part of the MCS team because they understand the delicate balance between bleeding and clotting and alteration of hemostasis with antithrombotic th...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
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