TH open : companion journal to thrombosis and haemostasis最新文献_第8页

Topically Applied Etamsylate: A New Orphan Drug for HHT-Derived Epistaxis (Antiangiogenesis through FGF Pathway Inhibition) 局部应用依坦磺酸:治疗hht源性鼻出血的孤儿药(通过抑制FGF途径抑制血管生成)

TH open : companion journal to thrombosis and haemostasis Pub Date : 2019-07-01 DOI: 10.1055/s-0039-1693710

Virginia Albiñana, G. Giménez-Gallego, Ángela García-Mato, P. Palacios, Lucía Recio-Poveda, A. Cuesta, J. Patier, L. Botella

{"title":"Topically Applied Etamsylate: A New Orphan Drug for HHT-Derived Epistaxis (Antiangiogenesis through FGF Pathway Inhibition)","authors":"Virginia Albiñana, G. Giménez-Gallego, Ángela García-Mato, P. Palacios, Lucía Recio-Poveda, A. Cuesta, J. Patier, L. Botella","doi":"10.1055/s-0039-1693710","DOIUrl":"https://doi.org/10.1055/s-0039-1693710","url":null,"abstract":"Abstract Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by recurrent and spontaneous epistaxis (nose bleeds), telangiectases on skin and mucosa, internal organ arteriovenous malformations, and dominant autosomal inheritance. Mutations in Endoglin and ACVRL1/ALK1, genes mainly expressed in endothelium, are responsible in 90% of the cases for the pathology. These genes are involved in the transforming growth factor-β(TGF-β) signaling pathway. Epistaxis remains as one of the most common symptoms impairing the quality of life of patients, becoming life-threatening in some cases. Different strategies have been used to decrease nose bleeds, among them is antiangiogenesis. The two main angiogenic pathways in endothelial cells depend on vascular endothelial growth factor and fibroblast growth factor (FGF). The present work has used etamsylate, the diethylamine salt of the 2,5-dihydroxybenzene sulfonate anion, also known as dobesilate, as a FGF signaling inhibitor. In endothelial cells, in vitro experiments show that etamsylate acts as an antiangiogenic factor, inhibiting wound healing and matrigel tubulogenesis. Moreover, etamsylate decreases phosphorylation of Akt and ERK1/2. A pilot clinical trial (EudraCT: 2016–003982–24) was performed with 12 HHT patients using a topical spray of etamsylate twice a day for 4 weeks. The epistaxis severity score (HHT-ESS) and other pertinent parameters were registered in the clinical trial. The significant reduction in the ESS scale, together with the lack of significant side effects, allowed the designation of topical etamsylate as a new orphan drug for epistaxis in HHT (EMA/OD/135/18).","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"3 1","pages":"e230 - e243"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78477500","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}

引用次数: 4

The Metabolites of the Dietary Flavonoid Quercetin Possess Potent Antithrombotic Activity, and Interact with Aspirin to Enhance Antiplatelet Effects 膳食类黄酮槲皮素的代谢物具有有效的抗血栓活性，并与阿司匹林相互作用增强抗血小板作用

TH open : companion journal to thrombosis and haemostasis Pub Date : 2019-07-01 DOI: 10.1055/s-0039-1694028

A. Stainer, P. Sasikumar, A. Bye, A. Unsworth, L. Holbrook, M. Tindall, J. Lovegrove, J. Gibbins

{"title":"The Metabolites of the Dietary Flavonoid Quercetin Possess Potent Antithrombotic Activity, and Interact with Aspirin to Enhance Antiplatelet Effects","authors":"A. Stainer, P. Sasikumar, A. Bye, A. Unsworth, L. Holbrook, M. Tindall, J. Lovegrove, J. Gibbins","doi":"10.1055/s-0039-1694028","DOIUrl":"https://doi.org/10.1055/s-0039-1694028","url":null,"abstract":"Abstract Quercetin, a dietary flavonoid, has been reported to possess antiplatelet activity. However, its extensive metabolism following ingestion has resulted in difficulty elucidating precise mechanisms of action. In this study, we aimed to characterize the antiplatelet mechanisms of two methylated metabolites of quercetin—isorhamnetin and tamarixetin—and explore potential interactions with aspirin. Isorhamnetin and tamarixetin inhibited human platelet aggregation, and suppressed activatory processes including granule secretion, integrin αIIbβ3 function, calcium mobilization, and spleen tyrosine kinase (Syk)/linker for activation of T cells (LAT) phosphorylation downstream of glycoprotein VI with similar potency to quercetin. All three flavonoids attenuated thrombus formation in an in vitro microfluidic model, and isoquercetin, a 3-O-glucoside of quercetin, inhibited thrombosis in a murine laser injury model. Isorhamnetin, tamarixetin, and quercetin enhanced the antiplatelet effects of aspirin more-than-additively in a plate-based aggregometry assay, reducing aspirin IC50 values by an order of magnitude, with this synergy maintained in a whole blood test of platelet function. Our data provide mechanistic evidence for the antiplatelet activity of two quercetin metabolites, isorhamnetin and tamarixetin, and suggest a potential antithrombotic role for these flavonoids. In combination with their interactions with aspirin, this may represent a novel avenue of investigation for the development of new antithrombotic strategies and management of current therapies.","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"47 1","pages":"e244 - e258"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74993471","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}

引用次数: 36

Trends and Inpatient Outcomes of Venous Thromboembolism-Related Admissions in Patients with Philadelphia-Negative Myeloproliferative Neoplasms 费城阴性骨髓增生性肿瘤患者静脉血栓栓塞相关入院的趋势和住院结果

TH open : companion journal to thrombosis and haemostasis Pub Date : 2019-07-01 DOI: 10.1055/s-0039-1692988

Vatsala Katiyar, Alok Uprety, A. Mendez-Hernandez, H. Fuentes, X. A. Andrade, M. Zia

{"title":"Trends and Inpatient Outcomes of Venous Thromboembolism-Related Admissions in Patients with Philadelphia-Negative Myeloproliferative Neoplasms","authors":"Vatsala Katiyar, Alok Uprety, A. Mendez-Hernandez, H. Fuentes, X. A. Andrade, M. Zia","doi":"10.1055/s-0039-1692988","DOIUrl":"https://doi.org/10.1055/s-0039-1692988","url":null,"abstract":"Abstract Background Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (MF), have a significant risk of venous thromboembolism (VTE). We aim to determine the trends in annual rates of VTE-related admissions, associated cost, length of stay (LOS), and in-hospital mortality in patients with MPN. Methods We identified patients with PV, ET, and MF from the Nationwide Inpatient Sample (NIS) database from 2006 to 2014 using ICD-9CM coding. Hospitalizations where VTE was among the top-three diagnoses were considered VTE-related. We compared in-hospital outcomes between VTE and non-VTE hospitalizations using chi-square and Mann–Whitney U-test and used linear regression for trend analysis. Results We identified 1,046,666 admissions with a diagnosis of MPN. Patients were predominantly white (65.6%), females (52.7%), with a median age of 66 years (range: 18–108). The predominant MPN was ET (54%). There was no difference in in-hospital mortality between groups (VTE: 3.4% vs. non-VTE: 3.2%; p = 0.12); however, VTE admissions had a longer LOS (median: 6 vs. 5 days; p < 0.01) and higher cost (median: VTE US$32,239 vs. 28,403; p ≤ 0.01). The annual rate of VTE admissions decreased over time (2006: 3.94% vs. 2014: 2.43%; p ≤ 0.01), compared with non-VTE–related admissions. Conclusion In our study, VTE-related admissions had similar in-hospital mortality as compared with non-VTE–related admissions. The rates of hospitalizations due to VTE have decreased over time but are associated with a higher cost and LOS. Newer risk assessment tools may assist in preventing VTE in high-risk patients and optimizing resource utilization.","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"31 1","pages":"e203 - e209"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89578682","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}

引用次数: 3

The International Prospective Glanzmann Thrombasthenia Registry: Pediatric Treatment and Outcomes 国际前瞻性Glanzmann血栓缺失登记:儿童治疗和结果

TH open : companion journal to thrombosis and haemostasis Pub Date : 2019-07-01 DOI: 10.1055/s-0039-1696657

R. Zotz, M. Poon, G. Di Minno, R. d’Oiron

{"title":"The International Prospective Glanzmann Thrombasthenia Registry: Pediatric Treatment and Outcomes","authors":"R. Zotz, M. Poon, G. Di Minno, R. d’Oiron","doi":"10.1055/s-0039-1696657","DOIUrl":"https://doi.org/10.1055/s-0039-1696657","url":null,"abstract":"Abstract Background Standard treatment for Glanzmann thrombasthenia (GT), a severe inherited bleeding disorder, is platelet transfusion. Recombinant activated factor VII (rFVIIa) is reported to be effective in GT with platelet antibodies and/or refractoriness to platelet transfusions. Methods We evaluated rFVIIa effectiveness and safety for the treatment and prevention of surgical and nonsurgical bleeding in children <18 years old, with or without platelet antibodies and/or refractoriness, as reported in the GT Registry (GTR). Data were used from the GTR, an international, multicenter, observational, postmarketing study of rFVIIa that prospectively collected data on the treatment and outcomes of bleeds in patients with GT. Only patients with a diagnosis of congenital GT were included in the registry. Results Between 2007 and 2011, 27 children were treated for 44 surgical procedures (minor: 36; major: 8); nonsurgical bleeds occurred in 104 patients (599 episodes: severe, 145; moderate, 454; spontaneous, 423; posttraumatic, 176). The effectiveness of treatment for minor procedures, major procedures, nonsurgical bleeds was 6/6, 1/1, and 75/84 for rFVIIa, 6/6, 2/2, and 64/76 for rFVIIa + antifibrinolytics (AF), 11/12, 1/1, and 162/214 for platelets ± AF, and 5/6, 0/3, and 33/45 for rFVIIa + platelets ± AF. In all, 25 adverse events were reported in children; no thromboembolic events were reported. Conclusion For all patients, regardless of platelet antibody or refractoriness status, rFVIIa, administered with or without platelets (± AF), provided effective hemostasis with a low frequency of adverse events in surgical, as well as nonsurgical, bleeding in patients with GT. clinicaltrials.gov identifier: NCT01476423.","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"28 1","pages":"e286 - e294"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75205084","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}

引用次数: 9

Coagulation Factor XIII in Cerebral Venous Thrombosis 凝血因子XIII在脑静脉血栓中的作用

TH open : companion journal to thrombosis and haemostasis Pub Date : 2019-07-01 DOI: 10.1055/s-0039-1693487

Bojun Li, M. Heldner, M. Arnold, J. Coutinho, S. Zuurbier, J. Meijers, H. Kohler, V. Schroeder

引用次数: 3