Journal of Thrombosis and Haemostasis最新文献

筛选
英文 中文
Pathogenic but sweet: factor VIII inhibitor hits the hot spot 致病但甜蜜:因子 VIII 抑制剂击中热点
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-08-20 DOI: 10.1016/j.jtha.2024.06.013
Vladimir N. Kolyadko
{"title":"Pathogenic but sweet: factor VIII inhibitor hits the hot spot","authors":"Vladimir N. Kolyadko","doi":"10.1016/j.jtha.2024.06.013","DOIUrl":"10.1016/j.jtha.2024.06.013","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cutting the Gordian knot of neutrophil extracellular traps research 解开中性粒细胞胞外捕获物研究的死结
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-08-20 DOI: 10.1016/j.jtha.2024.06.016
Frederik Denorme
{"title":"Cutting the Gordian knot of neutrophil extracellular traps research","authors":"Frederik Denorme","doi":"10.1016/j.jtha.2024.06.016","DOIUrl":"10.1016/j.jtha.2024.06.016","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
“2023 ISTH update of the 2022 ISTH guidelines for antithrombotic treatment in COVID-19”: reply "2023年ISTH对2022年ISTH COVID-19抗血栓治疗指南的更新":回复
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-08-20 DOI: 10.1016/j.jtha.2024.06.009
Sam Schulman , Helaine E. Resnick
{"title":"“2023 ISTH update of the 2022 ISTH guidelines for antithrombotic treatment in COVID-19”: reply","authors":"Sam Schulman , Helaine E. Resnick","doi":"10.1016/j.jtha.2024.06.009","DOIUrl":"10.1016/j.jtha.2024.06.009","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rapid and ordered cleavage of prothrombin by Hopsarin D in the absence of phospholipid membranes 在没有磷脂膜的情况下,啤酒花素 D 能快速有序地裂解凝血酶原。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-08-14 DOI: 10.1016/j.jtha.2024.07.027
Fatma Işık Üstok, Ty E. Adams, James A. Huntington
{"title":"Rapid and ordered cleavage of prothrombin by Hopsarin D in the absence of phospholipid membranes","authors":"Fatma Işık Üstok,&nbsp;Ty E. Adams,&nbsp;James A. Huntington","doi":"10.1016/j.jtha.2024.07.027","DOIUrl":"10.1016/j.jtha.2024.07.027","url":null,"abstract":"<div><h3>Background</h3><div>Thrombin is produced by the prothrombinase complex, composed of factor (f)Xa and fVa on a phospholipid (PL) membrane surface. Snakes of the Elapidae family have venom versions of these factors that cause coagulopathy in prey. Group C venoms contain both fⅩa and fⅤa orthologues. Group D venoms only contain a fXa orthologue and hijack fⅤa of the prey. Hopsarin D (HopD) is the venom fⅩa of the Stephen’s banded snake (<em>Hoplocephalus stephensii</em>).</div></div><div><h3>Objectives</h3><div>We set out to address the following: does HopD bind to human fⅤa with high affinity in the absence of PL? Does it process prothrombin through the meizothrombin pathway? Is the order of cleavage PL-dependent? Can HopD activate fⅤ?</div></div><div><h3>Methods</h3><div>We produced and characterized full-length and truncated HopD.</div></div><div><h3>Results</h3><div>HopD is only able to clot plasma that contains fⅤ and competes with human fⅩa for fⅤa binding. HopD binds to both human fⅤa and fⅤ with high affinity (dissociation constant, ∼10 nM), in contrast to fⅩa. HopD processes prothrombin down the meizothrombin route in the absence and presence of PL. Although HopD can bind to fⅤ, conversion to fⅤa is necessary for prothrombin processing. HopD initiates clotting in the blood of prey by activating fⅤ.</div></div><div><h3>Conclusion</h3><div>HopD binds to fⅤa with high affinity and rapidly activates prothrombin in the absence of PL, exclusively through the meizothrombin intermediate. HopD binds with high affinity to both fⅤa and fⅤ, suggesting that the B-domain does not sterically block fⅩa binding, but inhibits productive interaction in another way, and additionally prevents prothrombin binding.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endothelial protein disulfide isomerase A1 enhances membrane stiffness and platelet-endothelium interaction in hyperglycemia via SLC3A2 and LAMC1 内皮蛋白二硫化物异构酶-A1 通过 SLC3A2 和 LAMC1 增强高血糖时膜的硬度和血小板与内皮的相互作用
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-08-14 DOI: 10.1016/j.jtha.2024.08.001
Renato S. Gaspar , Álefe Roger Silva França , Percillia Victoria Santos Oliveira , Joel Félix Silva Diniz-Filho , Livia Teixeira , Iuri Cordeiro Valadão , Victor Debbas , Clenilton Costa dos Santos , Mariana Pereira Massafera , Silvina Odete Bustos , Luciana Magalhães Rebelo Alencar , Graziella Eliza Ronsein , Francisco R.M. Laurindo
{"title":"Endothelial protein disulfide isomerase A1 enhances membrane stiffness and platelet-endothelium interaction in hyperglycemia via SLC3A2 and LAMC1","authors":"Renato S. Gaspar ,&nbsp;Álefe Roger Silva França ,&nbsp;Percillia Victoria Santos Oliveira ,&nbsp;Joel Félix Silva Diniz-Filho ,&nbsp;Livia Teixeira ,&nbsp;Iuri Cordeiro Valadão ,&nbsp;Victor Debbas ,&nbsp;Clenilton Costa dos Santos ,&nbsp;Mariana Pereira Massafera ,&nbsp;Silvina Odete Bustos ,&nbsp;Luciana Magalhães Rebelo Alencar ,&nbsp;Graziella Eliza Ronsein ,&nbsp;Francisco R.M. Laurindo","doi":"10.1016/j.jtha.2024.08.001","DOIUrl":"10.1016/j.jtha.2024.08.001","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes carries an increased risk of cardiovascular disease and thromboembolic events. Upon endothelial dysfunction, platelets bind to endothelial cells to precipitate thrombus formation; however, it is unclear which surface proteins regulate platelet-endothelium interaction. We and others have shown that peri/epicellular protein disulfide isomerase A1 (pecPDI) influences the adhesion and migration of vascular cells.</div></div><div><h3>Objectives</h3><div>We investigated whether pecPDI regulates adhesion-related molecules on the surface of endothelial cells and platelets that influence the binding of these cells in hyperglycemia.</div></div><div><h3>Methods</h3><div>Immunofluorescence was used to assess platelet-endothelium interaction <em>in vitro,</em> cytoskeleton reorganization, and focal adhesions. Hydrogen peroxide production was assessed via Amplex Red assays (ThermoFisher Scientific). Cell biophysics was assessed using atomic force microscopy. Secreted proteins of interest were identified through proteomics (secretomics), and targets were knocked down using small interfering RNA. Protein disulfide isomerase A1 (PDI) contribution was assessed using whole-cell PDI or pecPDI inhibitors or small interfering RNA.</div></div><div><h3>Results</h3><div>Platelets of healthy donors adhered more onto hyperglycemic human umbilical vein endothelial cells (HUVECs). Endothelial, but not platelet, pecPDI regulated this effect. Hyperglycemic HUVECs showed marked cytoskeleton reorganization, increased H<sub>2</sub>O<sub>2</sub> production, and elongated focal adhesions. Indeed, hyperglycemic HUVECs were stiffer compared with normoglycemic cells. PDI and pecPDI inhibition reversed the abovementioned processes in hyperglycemic cells. A secretomics analysis revealed 8 proteins secreted in a PDI-dependent manner by hyperglycemic cells. Among these, we showed that genetic deletion of LAMC1 and SLC3A2 decreased platelet-endothelium interaction and did not potentiate the effects of PDI inhibitors.</div></div><div><h3>Conclusion</h3><div>Endothelial pecPDI regulates platelet-endothelium interaction in hyperglycemia through adhesion-related proteins and alterations in endothelial membrane biophysics.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hereditary antithrombin deficiency pilot project registry from the American Thrombosis and Hemostasis Network 美国血栓与止血网络(ATHN)遗传性抗凝血酶缺乏症试点项目登记处。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-08-14 DOI: 10.1016/j.jtha.2024.07.026
Maria T. DeSancho , Erin Suvar , Jonathan C. Roberts , Michael D. Tarantino , Jonathan Schwartz , Jessica Callis , Michael Recht
{"title":"Hereditary antithrombin deficiency pilot project registry from the American Thrombosis and Hemostasis Network","authors":"Maria T. DeSancho ,&nbsp;Erin Suvar ,&nbsp;Jonathan C. Roberts ,&nbsp;Michael D. Tarantino ,&nbsp;Jonathan Schwartz ,&nbsp;Jessica Callis ,&nbsp;Michael Recht","doi":"10.1016/j.jtha.2024.07.026","DOIUrl":"10.1016/j.jtha.2024.07.026","url":null,"abstract":"<div><h3>Background</h3><div>Patients with hereditary antithrombin deficiency (HAD) have an increased risk of venous thromboembolism (VTE). The American Thrombosis and Hemostasis Network (ATHN) 12: HAD Pilot Project established a registry to collect data on patients with HAD.</div></div><div><h3>Objectives</h3><div>To inform current practice and serve as a platform to design a multicenter global registry for patients with HAD.</div></div><div><h3>Methods</h3><div>The HAD registry was designed in 2020 to identify 100 patients with HAD receiving care at ATHN-affiliated centers. Demographics, type of HAD, thrombotic events, risk factors, anticoagulants, and antithrombin (AT) concentrate administration were recorded.</div></div><div><h3>Results</h3><div>Ninety-four patients were included; 65% were females; 51% had type 1 HAD. Mean age at diagnosis was 26 years (SD, 18 years); 61% had VTE: 55% deep vein thrombosis and 27% pulmonary embolisms. Eight patients had arterial thrombosis. Recurrent thrombosis occurred in 58.6% of patients (44.8%) despite anticoagulation. The main risk factor for thrombosis in females was estrogen. Direct oral anticoagulants were prescribed in 30%, heparin in 34%, and warfarin in 32%. There were 139 pregnancies. Low-molecular-weight heparin was administered in 33% and AT concentrate in 19% and 11% prior to and after delivery, respectively. Twelve patients developed thrombosis in pregnancy. Seventy-nine patients underwent 239 surgeries or procedures, mainly gastrointestinal and vascular. Overall, 35% of participants received AT concentrate without adverse events.</div></div><div><h3>Conclusion</h3><div>In ATHN 12, VTE was the predominant manifestation, frequently recurrent. There was a trend toward using direct oral anticoagulants. Low-molecular-weight heparin was administered in one-third of pregnancies and AT concentrate in one-fifth without adverse events. These data should encourage prospective studies to optimize the management of these patients.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rapid diagnosis of coagulopathies from vitamin K deficiency in a consecutive case cohort evaluated by comparative assessment of factor II by 1-stage assays with prothrombin time vs Ecarin reagents 通过凝血酶原时间与 Ecarin 试剂的单阶段测定法对因子 II 进行比较评估,评估连续病例队列中维生素 K 缺乏所致凝血病的快速诊断。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-08-14 DOI: 10.1016/j.jtha.2024.08.002
Alex Bourguignon , Natalie Mathews , Subia Tasneem , James Douketis , Catherine P.M. Hayward
{"title":"Rapid diagnosis of coagulopathies from vitamin K deficiency in a consecutive case cohort evaluated by comparative assessment of factor II by 1-stage assays with prothrombin time vs Ecarin reagents","authors":"Alex Bourguignon ,&nbsp;Natalie Mathews ,&nbsp;Subia Tasneem ,&nbsp;James Douketis ,&nbsp;Catherine P.M. Hayward","doi":"10.1016/j.jtha.2024.08.002","DOIUrl":"10.1016/j.jtha.2024.08.002","url":null,"abstract":"<div><h3>Background</h3><div>Vitamin K (VK) deficiency (VKD) impairs γ-carboxylation of VK-dependent factors (VKDFs), resulting in higher factor (F)II levels measured by Ecarin (FIIE) reagents (that convert des-γ-carboxylated FII to meizothrombin) than by prothrombin time (FII) reagents.</div></div><div><h3>Objectives</h3><div>To evaluate FII/FIIE abnormalities among patients assessed for coagulopathies and identify findings predictive of coagulopathy improvement after VK.</div></div><div><h3>Methods</h3><div>We retrospectively assessed consecutive cases from 2002 to 2021 with FII/FIIE tests and the sensitivity and specificity of FII/FIIE ratios and FIIE-FII differences for VKD defined as international normalized ratio correction/improvement of ≥0.5 after VK.</div></div><div><h3>Results</h3><div>Two hundred ninety-two patients (males, 58.2%; adults, 85.6%; median age, 73 years) were evaluated (84.2% hospitalized, 48.3% in intensive care, 71.6% with active liver disease, and 28% deceased at discharge) and 25% to 38% had FII/FIIE findings suggestive of VKD. Among 170 patients assessed for response to VK, FII/FIIE ratios of ≤0.84 to 0.91 and FIIE-FII differences of &gt;0.04 U/mL had similar modest sensitivity (47.7%-69.3%) and modest to good specificity (67.1%-91.5%) for VKD. FII/FIIE ratios of &lt;0.86, suggestive of VKD (sensitivity, 47.7%; specificity, 90.2%), were more common in patients deficient in only VKDF (<em>P</em> = .0001), but were detected in 16% with non-VKDF deficiencies. Low FIIE was commonly associated with active liver disease (<em>P</em> = .0002). Patients with and without probable VKD (based on FII/FIIE ratios of &lt;0.86) had similar mortality, bleeding, and rates of prothrombin complex concentrate and red cell transfusions (<em>P</em> ≥ .78), but fewer with probable VKD received plasma and fibrinogen replacement (<em>P</em> ≤ .024).</div></div><div><h3>Conclusion</h3><div>FII/FIIE comparison aids the diagnosis of VKD and predicts clinical responses to VK treatment among patients with coagulopathies.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Universal clinical decision support tool for thromboprophylaxis in hospitalized COVID-19 patients: post hoc analysis of the IMPROVE-DD cluster randomized trial COVID-19住院患者血栓预防的通用临床决策支持工具:IMPROVE-DD 群组随机试验的事后分析。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-08-14 DOI: 10.1016/j.jtha.2024.07.025
Mark Goldin , Nikolaos Tsaftaridis , Ioannis Koulas , Jeffrey Solomon , Michael Qiu , Tungming Leung , Kolton Smith , Kanta Ochani , Thomas McGinn , Alex C. Spyropoulos
{"title":"Universal clinical decision support tool for thromboprophylaxis in hospitalized COVID-19 patients: post hoc analysis of the IMPROVE-DD cluster randomized trial","authors":"Mark Goldin ,&nbsp;Nikolaos Tsaftaridis ,&nbsp;Ioannis Koulas ,&nbsp;Jeffrey Solomon ,&nbsp;Michael Qiu ,&nbsp;Tungming Leung ,&nbsp;Kolton Smith ,&nbsp;Kanta Ochani ,&nbsp;Thomas McGinn ,&nbsp;Alex C. Spyropoulos","doi":"10.1016/j.jtha.2024.07.025","DOIUrl":"10.1016/j.jtha.2024.07.025","url":null,"abstract":"<div><h3>Background</h3><div>Inpatient and extended postdischarge thromboprophylaxis of COVID-19 patients remains suboptimal despite antithrombotic guidelines.</div></div><div><h3>Objectives</h3><div>To determine whether a novel electronic health record–agnostic clinical decision support (CDS) tool incorporating the International Medical Prevention Registry on Venous Thromboembolism plus D-dimer (IMPROVE-DD) venous thromboembolism (VTE) scores increases appropriate inpatient and extended postdischarge thromboprophylaxis and improves outcomes in COVID-19 inpatients.</div></div><div><h3>Methods</h3><div>This post hoc analysis of the IMPROVE-DD cluster randomized trial evaluated thromboprophylaxis CDS among COVID-19 inpatients at 4 New York hospitals between December 21, 2020, and January 21, 2022. Hospitals were randomized 1:1 to CDS (intervention, <em>n</em> = 2) vs no CDS (usual care, <em>n</em> = 2). The primary outcome was rate of appropriate thromboprophylaxis. Secondary outcomes included rates of major thromboembolism, all-cause and VTE-related readmissions and death, major bleeding (MB), and all-cause mortality 30 days after discharge.</div></div><div><h3>Results</h3><div>Two thousand four hundred fifty-two COVID-19 inpatients were analyzed (CDS, 1355; no CDS, 1097). Mean age was 73.7 ± 9.37 years; 50.1% of participants were male. CDS adoption was 96.8% (intervention group). CDS was associated with increased appropriate at-discharge extended thromboprophylaxis (42.6% vs 28.8%; odds ratio [OR], 1.83; 95% CI, 1.39-2.41; <em>P</em> &lt; .001). CDS was associated with reduced VTE (OR, 0.54; 95% CI, 0.39-0.75; <em>P</em> &lt; .001), arterial thromboembolism (OR, 0.10; 95% CI, 0.01-0.81; <em>P</em> = .01), total thromboembolism (OR, 0.50; 95% CI, 0.36-0.69; <em>P</em> &lt; .001), and 30-day all-cause readmission/death (OR, 0.78; 95% CI, 0.62-0.99; <em>P</em> = .04). There were no differences in MB, VTE-related readmissions/death, or all-cause mortality.</div></div><div><h3>Conclusion</h3><div>Electronic health record–agnostic CDS incorporating IMPROVE-DD VTE scores had high adoption, was associated with increased appropriate at-discharge extended thromboprophylaxis, and reduced thromboembolism and all-cause readmission/death without increasing MB in COVID-19 inpatients.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel GPIb-independent platelet aggregation induced by botrocetin: implications for diagnosis and antithrombotic therapy 肉毒杆菌素诱导的新型 GPIb 依赖性血小板聚集:对诊断和抗血栓治疗的意义。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-08-13 DOI: 10.1016/j.jtha.2024.06.030
Chuanbin Shen , Daniel T. Mackeigan , Aron A. Shoara , Preeti Bhoria , Guangheng Zhu , Danielle Karakas , Wenjing Ma , Zi Yan Chen , Runjia Xu , Sladjana Slavkovic , Dachuan Zhang , Viktor Prifti , Zhenze Liu , Eric G. Cerenzia , Pingguo Chen , Miguel A.D. Neves , Huiyuan Li , Feng Xue , Renchi Yang , Junling Liu , Heyu Ni
{"title":"Novel GPIb-independent platelet aggregation induced by botrocetin: implications for diagnosis and antithrombotic therapy","authors":"Chuanbin Shen ,&nbsp;Daniel T. Mackeigan ,&nbsp;Aron A. Shoara ,&nbsp;Preeti Bhoria ,&nbsp;Guangheng Zhu ,&nbsp;Danielle Karakas ,&nbsp;Wenjing Ma ,&nbsp;Zi Yan Chen ,&nbsp;Runjia Xu ,&nbsp;Sladjana Slavkovic ,&nbsp;Dachuan Zhang ,&nbsp;Viktor Prifti ,&nbsp;Zhenze Liu ,&nbsp;Eric G. Cerenzia ,&nbsp;Pingguo Chen ,&nbsp;Miguel A.D. Neves ,&nbsp;Huiyuan Li ,&nbsp;Feng Xue ,&nbsp;Renchi Yang ,&nbsp;Junling Liu ,&nbsp;Heyu Ni","doi":"10.1016/j.jtha.2024.06.030","DOIUrl":"10.1016/j.jtha.2024.06.030","url":null,"abstract":"<div><h3>Background</h3><div>Snake venom botrocetin facilitates von Willebrand factor (VWF) binding to platelet GPIbα and has been widely used for the diagnosis of von Willebrand disease and GPIb-related disorders. Botrocetin is also commonly employed for the development/characterization of antithrombotics targeting the GPIb-VWF axis.</div></div><div><h3>Objectives</h3><div>To explore the alternative receptor(s)/mechanisms that participate in botrocetin-induced platelet aggregation.</div></div><div><h3>Methods</h3><div>The effects of botrocetin on platelet aggregation were examined using platelets from wild-type, <em>VWF</em>- and <em>fibrinogen</em>-deficient, <em>GPIbα</em>-deficient, <em>IL4Rα/GPIbα</em>-transgenic, <em>ITGA2B</em> and <em>ITGB3</em>-deficient mice, and Bernard–Soulier syndrome and healthy human samples. Platelet-fibrinogen and platelet-VWF interaction were measured using flow cytometry. GPIbα-VWF binding was evaluated utilizing enzyme-linked immunosorbent assay. Botrocetin-α<sub>IIb</sub>β<sub>3</sub> and botrocetin-GPIbα interactions were measured using enzyme-linked immunosorbent assay and fluorescence anisotropy assays. Heparinized whole blood from healthy donors was examined for thrombus formation and growth in a perfusion chamber.</div></div><div><h3>Results</h3><div>Botrocetin could induce aggregation of platelets from a Bernard–Soulier syndrome patient and <em>GPIbα</em>-deficient mice as well as platelets lacking the N-terminal extracellular domain of GPIbα. Botrocetin could interact with α<sub>IIb</sub>β<sub>3</sub> and facilitated α<sub>IIb</sub>β<sub>3</sub>-VWF interaction independent of GPIb. Botrocetin competitively bound to the ligand-binding domain of activated rather than resting α<sub>IIb</sub>β<sub>3</sub>. Although botrocetin-induced platelet aggregation requires VWF, strikingly, in the absence of VWF, botrocetin blocked fibrinogen and other ligand binding to α<sub>IIb</sub>β<sub>3</sub> and inhibited platelet aggregation and thrombus formation. Consistently, recombinant botrocetin defective in VWF binding inhibited α<sub>IIb</sub>β<sub>3</sub>- and GPIb-mediated platelet aggregation, spreading, and thrombus formation.</div></div><div><h3>Conclusion</h3><div>Our study provides insights into avoiding the misdiagnosis of GPIb-related disorders and developing botrocetin mutants as potential new antithrombotics that may simultaneously target both α<sub>IIb</sub>β<sub>3</sub> and GPIbα.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sensitivity and specificity of strategies to identify patients with hemostasis abnormalities leading to an increased risk of bleeding before scheduled intervention: the Hemorisk study 在计划干预前识别止血异常导致出血风险增加的患者策略的敏感性和特异性:Hemorisk 研究。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-08-10 DOI: 10.1016/j.jtha.2024.07.024
Nadine Ajzenberg , Dan Longrois , Dorothée Faille , Christian de Tymowski , Emmanuelle De Raucourt , Larbi Boudaoud , Stéphanie Sigaut , Isabelle Martin-Toutain , Mathieu Raux , Dominique Helley , Julien Josserand , Claire Flaujac , Jérome Duchemin , Charles-Marc Samama , Isabelle Gouin-Thibault , Hélène Beloeil , Edith Peynaud-Debayle , Hawa Keita-Meyer , Marie-Charlotte Bourrienne , Caroline Quintin , Florence Tubach
{"title":"Sensitivity and specificity of strategies to identify patients with hemostasis abnormalities leading to an increased risk of bleeding before scheduled intervention: the Hemorisk study","authors":"Nadine Ajzenberg ,&nbsp;Dan Longrois ,&nbsp;Dorothée Faille ,&nbsp;Christian de Tymowski ,&nbsp;Emmanuelle De Raucourt ,&nbsp;Larbi Boudaoud ,&nbsp;Stéphanie Sigaut ,&nbsp;Isabelle Martin-Toutain ,&nbsp;Mathieu Raux ,&nbsp;Dominique Helley ,&nbsp;Julien Josserand ,&nbsp;Claire Flaujac ,&nbsp;Jérome Duchemin ,&nbsp;Charles-Marc Samama ,&nbsp;Isabelle Gouin-Thibault ,&nbsp;Hélène Beloeil ,&nbsp;Edith Peynaud-Debayle ,&nbsp;Hawa Keita-Meyer ,&nbsp;Marie-Charlotte Bourrienne ,&nbsp;Caroline Quintin ,&nbsp;Florence Tubach","doi":"10.1016/j.jtha.2024.07.024","DOIUrl":"10.1016/j.jtha.2024.07.024","url":null,"abstract":"<div><h3>Background</h3><div>Preoperative identification of patients with hemostasis abnormalities leading to an increased bleeding risk is based on routine hemostasis tests: prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet count. Because of their low predictive performance, guidelines recommend replacing them with structured bleeding risk questionnaires, but none is validated in this population.</div></div><div><h3>Objectives</h3><div>To assess the diagnostic accuracy of 3 strategies, performed at the preanesthesia visit before scheduled interventions, and to identify patients with hemostasis abnormalities leading to an increased bleeding risk</div></div><div><h3>Methods</h3><div>A multicenter study was performed in 7 French academic hospitals, involving patients scheduled for surgical intervention, without antiplatelet/anticoagulant treatment. The 3 strategies consisted of 1-a structured screening questionnaire; 2-PT, APTT, and platelet count ordered in selected patients; and 3-systematic PT, APTT, and platelet count. The reference standard comprised von Willebrand factor activity/antigen, factor (F)VIII, FIX, FXI, platelet function analyzer, and, when required, FII, FV, FX, and FVII and hemostasis consultation.</div></div><div><h3>Results</h3><div>Eighteen (1.2%) of 1484 patients had a hemostasis abnormality leading to an increased bleeding risk according to reference standard. In the overall cohort, sensitivity of the questionnaire-based strategy was 50% (95% CI, 26%-74%; specificity, 87% [95% CI, 85%-88%]); sensitivity was 0% (95% CI, 0%-41%) in men vs 82% (95% CI, 48%-98%) in women. For selective routine tests, sensitivity was 33% (95% CI, 13%-59%) and specificity 97% (95% CI, 96%-98%). Corresponding values for systematic routine tests were 44% (95% CI, 22%-69%) and 93% (95% CI, 91%-94%).</div></div><div><h3>Conclusion</h3><div>Sensitivity was low for all 3 strategies investigated. The structured screening questionnaire had clinically acceptable diagnostic accuracy only in women.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信