Journal of Thrombosis and Haemostasis最新文献

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Meta-analyzing antithrombotic therapy in myeloproliferative neoplasm–related splanchnic vein thrombosis: a first step in understanding a rare complication of a rare disease
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-12-01 DOI: 10.1016/j.jtha.2024.09.015
Douglas Tremblay
{"title":"Meta-analyzing antithrombotic therapy in myeloproliferative neoplasm–related splanchnic vein thrombosis: a first step in understanding a rare complication of a rare disease","authors":"Douglas Tremblay","doi":"10.1016/j.jtha.2024.09.015","DOIUrl":"10.1016/j.jtha.2024.09.015","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3395-3396"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748074","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
Early thrombus formation is required for eccentric and heterogeneous neointimal hyperplasia under disturbed flow 在血流紊乱的情况下,偏心和异源性新内膜增生需要早期血栓形成。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-12-01 DOI: 10.1016/j.jtha.2024.07.028
Hualong Bai , Zhuo Li , Weichang Zhang , Carly Thaxton , Yuichi Ohashi , Luis Gonzalez , Masaki Kano , Bogdan Yatsula , John Hwa , Alan Dardik
{"title":"Early thrombus formation is required for eccentric and heterogeneous neointimal hyperplasia under disturbed flow","authors":"Hualong Bai ,&nbsp;Zhuo Li ,&nbsp;Weichang Zhang ,&nbsp;Carly Thaxton ,&nbsp;Yuichi Ohashi ,&nbsp;Luis Gonzalez ,&nbsp;Masaki Kano ,&nbsp;Bogdan Yatsula ,&nbsp;John Hwa ,&nbsp;Alan Dardik","doi":"10.1016/j.jtha.2024.07.028","DOIUrl":"10.1016/j.jtha.2024.07.028","url":null,"abstract":"<div><h3>Background</h3><div>Anticoagulation and antiplatelet therapy effectively inhibit neointimal hyperplasia (NIH) in both arterial and venous systems but not in arteriovenous fistulae (AVF). The main site of AVF failure is the juxta-anastomotic area that is characterized by disturbed flow compared with laminar flow in the arterial inflow and the venous outflow.</div></div><div><h3>Objectives</h3><div>We hypothesized that early thrombus formation is required for eccentric and heterogeneous NIH in the presence of disturbed flow.</div></div><div><h3>Methods</h3><div>Needle puncture and sutured AVF were created in C57BL/6 mice, in PF4-Cre × mT/mG reporter mice, and in Wistar rats. Human AVF samples were second-stage basilic vein transpositions. The tissues were examined by histology, immunofluorescence, immunohistochemistry, and en face staining.</div></div><div><h3>Results</h3><div>In the presence of disturbed flow, both mouse and human AVF showed eccentric and heterogeneous NIH. Maladapted vein wall was characterized by eccentric and heterogeneous neointima that was composed of a different abundance of thrombus and smooth muscle cells. PF4-cre × mT/mG reporter mice AVF showed that green fluorescent protein-labeled platelets deposit on the wall directly facing the fistula exit with endothelial cell loss and continue to accumulate in the presence of disturbed flow. Neither disturbed flow with limited endothelial cell loss nor nondisturbed flow induced heterogeneous neointima in different animal models.</div></div><div><h3>Conclusion</h3><div>Early thrombus contributes to late heterogeneous NIH in the presence of disturbed flow. Disturbed flow, large area of endothelial cell loss, and thrombus formation are critical to form eccentric and heterogeneous NIH. Categorization of adapted or maladapted walls may be helpful for therapy targeting heterogeneous NIH.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3614-3628"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036170","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
Lack of factor VIII detection in humans and dogs with an intron 22 inversion challenges hypothesis regarding inhibitor risk 人类和狗体内未检测到 FVIII 内含子-22 倒位,这对有关抑制剂风险的假设提出了挑战。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-12-01 DOI: 10.1016/j.jtha.2024.08.007
Pooja Vir , Devi Gunasekera , Batsukh Dorjbal , Dennis McDaniel , Atul Agrawal , Elizabeth P. Merricks , Margaret V. Ragni , Cindy A. Leissinger , Allen I. Stering , Kenneth Lieuw , Timothy C. Nichols , Kathleen P. Pratt
{"title":"Lack of factor VIII detection in humans and dogs with an intron 22 inversion challenges hypothesis regarding inhibitor risk","authors":"Pooja Vir ,&nbsp;Devi Gunasekera ,&nbsp;Batsukh Dorjbal ,&nbsp;Dennis McDaniel ,&nbsp;Atul Agrawal ,&nbsp;Elizabeth P. Merricks ,&nbsp;Margaret V. Ragni ,&nbsp;Cindy A. Leissinger ,&nbsp;Allen I. Stering ,&nbsp;Kenneth Lieuw ,&nbsp;Timothy C. Nichols ,&nbsp;Kathleen P. Pratt","doi":"10.1016/j.jtha.2024.08.007","DOIUrl":"10.1016/j.jtha.2024.08.007","url":null,"abstract":"<div><h3>Background</h3><div>Almost half of severe hemophilia A (HA) cases are caused by an intron 22 inversion (Int22Inv) mutation, which truncates the 26-exon <em>F8</em> messenger RNA (mRNA) after exon 22. Another <em>F8</em> transcript, <em>F8</em><sub><em>B</em></sub>, is initiated from within <em>F8</em>-intron-22. <em>F8</em><sub><em>B</em></sub> mRNA consists of a short exon spliced to exons 23 to 26 and is expressed in multiple human cell types. It has been hypothesized that Int22Inv patients have self-tolerance to partial factor (F)VIII proteins expressed from these 2 transcripts. FVIII is expressed in endothelial cells, primarily in the liver and lungs. Several studies have reported FVIII expression in other cell types, although this has been controversial.</div></div><div><h3>Objectives</h3><div>To determine if partial FVIII proteins are expressed from intron 22–inverted and/or <em>F8</em><sub><em>B</em></sub> mRNA and if FVIII is expressed in nonendothelial cells.</div></div><div><h3>Methods</h3><div>A panel of FVIII-specific antibodies was validated and employed to label FVIII in cells and tissues and for immunoprecipitation followed by western blots and mass spectrometry proteomics analysis.</div></div><div><h3>Results</h3><div>Immunofluorescent staining localized FVIII to endothelial cells in liver sections from non-HA but not HA-Int22Inv dogs. Neither FVIII nor FVIII<sub>B</sub> was detected in human peripheral blood mononuclear cells, B cell or T cell lines, or cell lines expanded from peripheral blood mononuclear cells, whereas FVIII antigen and activity were readily detected in primary nonhemophilic liver sinusoidal endothelial cells.</div></div><div><h3>Conclusion</h3><div>If FVIII is expressed in nonendothelial cells or if partial FVIII proteins are expressed in HA-Int22Inv, the concentrations are below the detection limits of these sensitive assays. Our results argue against promotion of immune tolerance through expression of partial FVIII proteins in Int-22Inv patients.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3415-3430"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133043","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
Clinical validation and application of targeted long-range polymerase chain reaction and long-read sequencing–based analysis for hemophilia: experience from a hemophilia treatment center in China 基于长程定量 PCR 和长序列测序的血友病靶向分析的临床验证和应用:来自中国一家血友病治疗中心的经验。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-12-01 DOI: 10.1016/j.jtha.2024.08.013
Meizhen Shi , Yunting Ma , Xianwei Peng , Xu Zhou , Zifeng Cheng , Bobo Xie , Xianda Wei , Chunrong Gui , Aiping Mao , Wenting Lin , Jiefeng Luo , Yinghui Lai , Baoheng Gui
{"title":"Clinical validation and application of targeted long-range polymerase chain reaction and long-read sequencing–based analysis for hemophilia: experience from a hemophilia treatment center in China","authors":"Meizhen Shi ,&nbsp;Yunting Ma ,&nbsp;Xianwei Peng ,&nbsp;Xu Zhou ,&nbsp;Zifeng Cheng ,&nbsp;Bobo Xie ,&nbsp;Xianda Wei ,&nbsp;Chunrong Gui ,&nbsp;Aiping Mao ,&nbsp;Wenting Lin ,&nbsp;Jiefeng Luo ,&nbsp;Yinghui Lai ,&nbsp;Baoheng Gui","doi":"10.1016/j.jtha.2024.08.013","DOIUrl":"10.1016/j.jtha.2024.08.013","url":null,"abstract":"<div><h3>Background</h3><div>Targeted long-read sequencing (LRS) is expected to comprehensively analyze diverse complex variants in hemophilia A (HA) and hemophilia B (HB) caused by the <em>F8</em> and <em>F9</em> genes, respectively. However, its clinical applicability still requires extensive validation.</div></div><div><h3>Objectives</h3><div>To evaluate the clinical applicability of targeted LRS-based analysis compared with routine polymerase chain reaction (PCR)–based methods.</div></div><div><h3>Methods</h3><div>Gene variants of retrieved subjects were retrospectively and prospectively analyzed. Whole-genome sequencing was performed to further analyze undiagnosed cases. Breakpoints of novel genomic rearrangements were mapped and validated using long-distance PCR and long-range PCR combined with sequencing.</div></div><div><h3>Results</h3><div>In total, 122 subjects were retrieved. In retrospective analysis of the 90 HA cases, HA-LRS assay showed consistent results in 84 cases compared with routine methods and characterized 6 large deletions with their exact breakpoints confirmed by further validation in 6 cases (routine methods only presented failure in amplifying the involved exons). In prospective analysis of the 21 HA subjects, 20 variants of <em>F8</em> were identified in 20 cases. For the remaining HA patient, no duplication/deletion or single-nucleotide variant (SNV)/insertion and deletion (InDel) was found, but a potential recombination involving exons 14 and 21 of <em>F8</em> was observed by LRS. Whole-genome sequencing analysis and further verification defined a 30 478 base pairs (bp) tandem repeat involving exons 14 to 21 of <em>F8</em>. Among the 11 HB patients, HB-LRS analysis detected 11 SNVs/InDels in <em>F9</em>, consistent with routine methods.</div></div><div><h3>Conclusion</h3><div>Targeted LRS-based analysis was efficient and comprehensive in identifying SNVs/InDels and genomic rearrangements of hemophilia genes, especially when we first expanded the panel to include <em>F9</em>. However, further investigation for complex gross rearrangement is still essential.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3431-3447"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182689","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
The eccentric nature of the neointima
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-12-01 DOI: 10.1016/j.jtha.2024.08.005
Filipe F. Stoyell-Conti , Laisel Martinez , Roberto I. Vazquez-Padron
{"title":"The eccentric nature of the neointima","authors":"Filipe F. Stoyell-Conti ,&nbsp;Laisel Martinez ,&nbsp;Roberto I. Vazquez-Padron","doi":"10.1016/j.jtha.2024.08.005","DOIUrl":"10.1016/j.jtha.2024.08.005","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3397-3399"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748075","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
Shifting focus from venous to arterial thromboembolism in patients with cancer
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-12-01 DOI: 10.1016/j.jtha.2024.09.020
Anniek Strijdhorst , Nick van Es
{"title":"Shifting focus from venous to arterial thromboembolism in patients with cancer","authors":"Anniek Strijdhorst ,&nbsp;Nick van Es","doi":"10.1016/j.jtha.2024.09.020","DOIUrl":"10.1016/j.jtha.2024.09.020","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3403-3405"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748178","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
RUNX1 isoforms regulate RUNX1 and target genes differentially in platelets-megakaryocytes: association with clinical cardiovascular events RUNX1 异构体对血小板-巨核细胞中的 RUNX1 和靶基因有不同的调控作用:与临床心血管事件的关系
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-12-01 DOI: 10.1016/j.jtha.2024.07.032
Liying Guan , Deepak Voora , Rachel Myers , Fabiola Del Carpio-Cano , A. Koneti Rao
{"title":"RUNX1 isoforms regulate RUNX1 and target genes differentially in platelets-megakaryocytes: association with clinical cardiovascular events","authors":"Liying Guan ,&nbsp;Deepak Voora ,&nbsp;Rachel Myers ,&nbsp;Fabiola Del Carpio-Cano ,&nbsp;A. Koneti Rao","doi":"10.1016/j.jtha.2024.07.032","DOIUrl":"10.1016/j.jtha.2024.07.032","url":null,"abstract":"<div><h3>Background</h3><div>Hematopoietic transcription factor RUNX1 is expressed from proximal P2 and distal P1 promoters to yield isoforms RUNX1 B and C, respectively. The roles of these isoforms in RUNX1 autoregulation and downstream gene regulation in megakaryocytes and platelets are unknown.</div></div><div><h3>Objectives</h3><div>To understand the regulation of <em>RUNX1</em> and its target genes by RUNX1 isoforms.</div></div><div><h3>Methods</h3><div>We performed studies on RUNX1 isoforms in megakaryocytic human erythroleukemia (HEL) cells and HeLa cells (lack endogenous RUNX1), in platelets from 85 healthy volunteers administered aspirin or ticagrelor, and on the association of RUNX1 target genes with acute events in 587 patients with cardiovascular disease (CVD).</div></div><div><h3>Results</h3><div>In chromatin immunoprecipitation and luciferase promoter assays, RUNX1 isoforms B and C bound and regulated P1 and P2 promoters. In HeLa cells, RUNX1B decreased and RUNX1C increased P1 and P2 activities, respectively. In HEL cells, RUNX1B overexpression decreased RUNX1C and RUNX1A expression; RUNX1C increased RUNX1B and RUNX1A. RUNX1B and RUNX1C regulated target genes (<em>MYL9</em>, <em>F13A1</em>, <em>PCTP</em>, <em>PDE5A</em>, and others) differentially in HEL cells. In platelets, <em>RUNX1B</em> transcripts (by RNA sequencing) correlated negatively with <em>RUNX1C</em> and <em>RUNX1A</em>; <em>RUNX1C</em> correlated positively with <em>RUNX1A</em>. <em>RUNX1B</em> correlated positively with <em>F13A1</em>, <em>PCTP</em>, <em>PDE5A</em>, <em>RAB1B</em>, and others, and negatively with <em>MYL9</em>. In our previous studies, <em>RUNX1C</em> transcripts in whole blood were protective against acute events in CVD patients. We found that higher expression of RUNX1 targets <em>F13A1</em> and <em>RAB31</em> associated with acute events.</div></div><div><h3>Conclusion</h3><div>RUNX1 isoforms B and C autoregulate <em>RUNX1</em> and regulate downstream genes in a differential manner, and this is associated with acute events in CVD.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3581-3598"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055959","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
Treatment of atrial fibrillation and venous thromboembolism with factor Xa inhibitors in severely obese patients 用 Xa 因子抑制剂治疗严重肥胖患者的心房颤动和静脉血栓栓塞。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-12-01 DOI: 10.1016/j.jtha.2024.08.009
Paul Dobry , Stephanie B. Edwin , Brian Haymart , Geoffrey D. Barnes , Scott Kaatz , Mona A. Ali , Christopher Giuliano
{"title":"Treatment of atrial fibrillation and venous thromboembolism with factor Xa inhibitors in severely obese patients","authors":"Paul Dobry ,&nbsp;Stephanie B. Edwin ,&nbsp;Brian Haymart ,&nbsp;Geoffrey D. Barnes ,&nbsp;Scott Kaatz ,&nbsp;Mona A. Ali ,&nbsp;Christopher Giuliano","doi":"10.1016/j.jtha.2024.08.009","DOIUrl":"10.1016/j.jtha.2024.08.009","url":null,"abstract":"<div><h3>Background</h3><div>A paucity of data exists to support the use of factor (F)Xa inhibitors in severely obese patients with a weight of ≥150 kg or body mass index (BMI) of ≥50 kg/m<sup>2</sup>.</div></div><div><h3>Objectives</h3><div>The purpose of this study was to evaluate whether FXa inhibitors are as safe and effective as warfarin for the treatment of atrial fibrillation (AF) and/or venous thromboembolism (VTE) in individuals with a BMI of ≥50 kg/m<sup>2</sup> and/or weight of ≥150 kg.</div></div><div><h3>Methods</h3><div>This was a multicenter retrospective cohort study of severely obese adult patients with AF and/or VTE treated with a FXa inhibitor or warfarin. The primary effectiveness outcome was composite odds of stroke, systemic embolism, or VTE; the primary safety outcome was odds of major bleeding. Secondary outcomes included incidence of stroke or systemic embolism, VTE, major bleeding, clinically relevant nonmajor bleeding, all-cause mortality, change in anticoagulation, and total number of hospital encounters. Outcomes were assessed for 12 months following initiation of study drug.</div></div><div><h3>Results</h3><div>A total of 1736 patients were included. The mean weight and BMI of the overall cohort were 164.4 kg and 54.6 kg/m<sup>2</sup>, respectively. There was no difference in odds of stroke, systemic embolism or VTE (odds ratio, 1.005; 95% CI, 0.6-1.68), or major bleeding (odds ratio, 0.9; 95% CI, 0.47-1.7) between groups.</div></div><div><h3>Conclusion</h3><div>These data suggest that apixaban and rivaroxaban are safe and effective alternatives to warfarin for the treatment of AF and/or VTE in individuals with a BMI of ≥50 kg/m<sup>2</sup> and/or weight of ≥150 kg.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3500-3509"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145870","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
Low von Willebrand factor—unraveling an enigma wrapped in a conundrum 低 VWF--揭开谜团中的谜底。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-12-01 DOI: 10.1016/j.jtha.2024.08.015
James S. O’Donnell , Ross I. Baker , Ferdows Atiq
{"title":"Low von Willebrand factor—unraveling an enigma wrapped in a conundrum","authors":"James S. O’Donnell ,&nbsp;Ross I. Baker ,&nbsp;Ferdows Atiq","doi":"10.1016/j.jtha.2024.08.015","DOIUrl":"10.1016/j.jtha.2024.08.015","url":null,"abstract":"<div><div>The 2021 ASH ISTH NHF WFH guidelines recommendation that patients with von Willebrand factor (VWF) levels of 30 to 50 IU/dL and an increased bleeding phenotype be categorized as type 1 von Willebrand disease (VWD) rather than Low VWF has proved controversial. However, in support of that decision, recent data have demonstrated that individuals with partial quantitative VWF deficiency exhibit an age-dependent evolving phenotype and confirmed that Low VWF represents a subgroup within heterogeneous type 1 VWD. Nonetheless, type 1 VWD heterogeneity continues to pose significant diagnostic challenges. In this Forum article, we address outstanding issues critical to preventing the inappropriate overdiagnosis of type 1 VWD while maximizing access to healthcare and minimizing diagnostic delays. In addition, we propose an algorithm for type 1 VWD diagnosis. This algorithm pays special attention to individuals with plasma VWF levels in the 30 to 50 IU/dL range who have no or minimal bleeding history and have not yet been exposed to significant hemostatic challenges.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3383-3388"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251215","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
Enhanced venous thrombosis and hypercoagulability in murine and human metabolic dysfunction-associated steatohepatitis 小鼠和人类代谢功能障碍相关性脂肪性肝炎的静脉血栓形成和高凝状态增强
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-12-01 DOI: 10.1016/j.jtha.2024.08.023
Nilesh Pandey , Sumit Kumar Anand , Harpreet Kaur , Koral S.E. Richard , Lakshmi Chandaluri , Megan E. Butler , Xiaolu Zhang , Brenna Pearson-Gallion , Sumati Rohilla , Sandeep Das , Tarek Magdy , Palaniappan Sethu , Kelley G. Núñez , A. Wayne Orr , Karen Y. Stokes , Paul T. Thevenot , Ari J. Cohen , Oren Rom , Nirav Dhanesha
{"title":"Enhanced venous thrombosis and hypercoagulability in murine and human metabolic dysfunction-associated steatohepatitis","authors":"Nilesh Pandey ,&nbsp;Sumit Kumar Anand ,&nbsp;Harpreet Kaur ,&nbsp;Koral S.E. Richard ,&nbsp;Lakshmi Chandaluri ,&nbsp;Megan E. Butler ,&nbsp;Xiaolu Zhang ,&nbsp;Brenna Pearson-Gallion ,&nbsp;Sumati Rohilla ,&nbsp;Sandeep Das ,&nbsp;Tarek Magdy ,&nbsp;Palaniappan Sethu ,&nbsp;Kelley G. Núñez ,&nbsp;A. Wayne Orr ,&nbsp;Karen Y. Stokes ,&nbsp;Paul T. Thevenot ,&nbsp;Ari J. Cohen ,&nbsp;Oren Rom ,&nbsp;Nirav Dhanesha","doi":"10.1016/j.jtha.2024.08.023","DOIUrl":"10.1016/j.jtha.2024.08.023","url":null,"abstract":"<div><h3>Background</h3><div>Patients with metabolic dysfunction-associated steatohepatitis (MASH) are at an increased risk of developing venous thromboembolic events, including deep vein thrombosis (DVT). To date, the study of DVT in MASH has been hampered by the lack of reliable models that mimic the pathologic aspects of human disease.</div></div><div><h3>Objectives</h3><div>To evaluate DVT severity and hypercoagulability in murine and human MASH.</div></div><div><h3>Methods</h3><div>Transcriptional changes in the liver, plasma markers of coagulation, and DVT severity were evaluated in mice fed a standard chow diet or a high-fructose, high-fat, and high-cholesterol MASH diet for 24 weeks. Plasma analyses of coagulation markers and thrombin generation assays were performed in a well-characterized cohort of patients with or without MASH.</div></div><div><h3>Results</h3><div>Mice fed the MASH diet developed steatohepatitis and fibrosis, mimicking human MASH. Liver RNA sequencing revealed a significant upregulation of pathways related to inflammation and coagulation concomitant with increased levels of plasma coagulation markers including increased prothrombin fragment 1+2, thrombin-antithrombin complex, plasminogen activator inhibitor-1 levels, and endothelin 1. MASH exacerbated DVT severity in mice, as evidenced by increased thrombus weight and higher thrombosis incidence (15/15 vs 11/15 in controls, <em>P</em> = .0317). Higher endothelin 1 release and increased apoptosis were found in endothelial cells stimulated with supernatants of palmitate-stimulated HepG2 cells. Patients with MASH exhibited increased levels of plasma coagulation markers and delayed thrombin generation.</div></div><div><h3>Conclusion</h3><div>We report enhanced DVT severity and hypercoagulability, both in murine and human MASH. Our model of MASH-DVT can facilitate a better understanding of the fundamental mechanisms leading to increased venous thromboembolic events in patients with MASH.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3572-3580"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289961","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}
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