急性和慢性肝病患者血浆纤溶酶介导的血管性血友病因子蛋白水解

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2025-08-01 DOI:10.1016/j.rpth.2025.103166

Hinde El Otmani , Marilena Stamouli , Jelle Adelmeijer , William Bernal , Coen Maas , Vishal C. Patel , Ton Lisman

{"title":"急性和慢性肝病患者血浆纤溶酶介导的血管性血友病因子蛋白水解","authors":"Hinde El Otmani , Marilena Stamouli , Jelle Adelmeijer , William Bernal , Coen Maas , Vishal C. Patel , Ton Lisman","doi":"10.1016/j.rpth.2025.103166","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>In patients with acute and chronic liver disease, von Willebrand factor (VWF) antigen levels are markedly elevated, whereas a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS13) activity is often reduced. The role of VWF proteolysis by other proteases, such as plasmin, remains unclear.</div></div><div><h3>Objectives</h3><div>To investigate whether plasmin-mediated VWF cleavage occurs in patients with acute and chronic liver disease and to assess its association with VWF parameters, ADAMTS13 activity, and fibrinolytic markers.</div></div><div><h3>Methods</h3><div>Plasma samples from 191 patients with stable or decompensated cirrhosis, acute liver failure or acute liver injury, acute-on-chronic liver failure, or sepsis without underlying chronic liver disease and 41 healthy controls were analyzed. VWF antigen and collagen-binding activity, ADAMTS13 antigen and activity, ADAMTS13-cleaved VWF, plasmin-cleaved VWF (cVWF), plasmin-α2-antiplasmin complexes, and D-dimer were measured by ELISA.</div></div><div><h3>Results</h3><div>VWF antigen levels were higher in all patient groups and increased with disease severity. VWF activity was also elevated but was not proportional to VWF antigen level. ADAMTS13 activity and specific activity decreased with worsening disease. cVWF was undetectable in healthy controls and patients with stable cirrhosis but was increased in patients with decompensated cirrhosis, acute liver failure or injury, and acute-on-chronic liver failure. cVWF levels correlated with D-dimer but not with plasmin-α2-antiplasmin complexes or VWF activity.</div></div><div><h3>Conclusion</h3><div>cVWF is detectable in patients with decompensated cirrhosis, acute liver failure or injury, and acute-on-chronic liver failure but not in those with stable cirrhosis or healthy individuals. Its association with D-dimer supports a link with fibrinolytic activation. These findings suggest that cVWF may reflect disease severity or ongoing microvascular thrombosis in patients with advanced liver disease.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 6","pages":"Article 103166"},"PeriodicalIF":3.4000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Plasmin-mediated proteolysis of von Willebrand factor in patients with acute and chronic liver disease\",\"authors\":\"Hinde El Otmani , Marilena Stamouli , Jelle Adelmeijer , William Bernal , Coen Maas , Vishal C. Patel , Ton Lisman\",\"doi\":\"10.1016/j.rpth.2025.103166\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>In patients with acute and chronic liver disease, von Willebrand factor (VWF) antigen levels are markedly elevated, whereas a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS13) activity is often reduced. The role of VWF proteolysis by other proteases, such as plasmin, remains unclear.</div></div><div><h3>Objectives</h3><div>To investigate whether plasmin-mediated VWF cleavage occurs in patients with acute and chronic liver disease and to assess its association with VWF parameters, ADAMTS13 activity, and fibrinolytic markers.</div></div><div><h3>Methods</h3><div>Plasma samples from 191 patients with stable or decompensated cirrhosis, acute liver failure or acute liver injury, acute-on-chronic liver failure, or sepsis without underlying chronic liver disease and 41 healthy controls were analyzed. VWF antigen and collagen-binding activity, ADAMTS13 antigen and activity, ADAMTS13-cleaved VWF, plasmin-cleaved VWF (cVWF), plasmin-α2-antiplasmin complexes, and D-dimer were measured by ELISA.</div></div><div><h3>Results</h3><div>VWF antigen levels were higher in all patient groups and increased with disease severity. VWF activity was also elevated but was not proportional to VWF antigen level. ADAMTS13 activity and specific activity decreased with worsening disease. cVWF was undetectable in healthy controls and patients with stable cirrhosis but was increased in patients with decompensated cirrhosis, acute liver failure or injury, and acute-on-chronic liver failure. cVWF levels correlated with D-dimer but not with plasmin-α2-antiplasmin complexes or VWF activity.</div></div><div><h3>Conclusion</h3><div>cVWF is detectable in patients with decompensated cirrhosis, acute liver failure or injury, and acute-on-chronic liver failure but not in those with stable cirrhosis or healthy individuals. Its association with D-dimer supports a link with fibrinolytic activation. These findings suggest that cVWF may reflect disease severity or ongoing microvascular thrombosis in patients with advanced liver disease.</div></div>\",\"PeriodicalId\":20893,\"journal\":{\"name\":\"Research and Practice in Thrombosis and Haemostasis\",\"volume\":\"9 6\",\"pages\":\"Article 103166\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Research and Practice in Thrombosis and Haemostasis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S247503792500490X\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Research and Practice in Thrombosis and Haemostasis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S247503792500490X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

在急性和慢性肝病患者中，血管性血友病因子（VWF）抗原水平显著升高，而具有1型凝血反应蛋白基元的崩解素和金属蛋白酶13成员（ADAMTS13）活性经常降低。其他蛋白酶（如纤溶酶）对VWF蛋白的水解作用尚不清楚。目的探讨纤溶酶介导的VWF切割是否发生在急慢性肝病患者中，并评估其与VWF参数、ADAMTS13活性和纤溶标志物的关系。方法分析191例稳定型或失代偿性肝硬化、急性肝功能衰竭或急性肝损伤、急性伴慢性肝功能衰竭或败血症（无基础慢性肝病）患者和41例健康对照者的血浆。ELISA法测定VWF抗原及胶原结合活性、ADAMTS13抗原及活性、ADAMTS13裂解VWF、纤溶蛋白裂解VWF （cVWF）、纤溶蛋白-α2-抗纤溶蛋白复合物、d -二聚体。结果各组vwf抗原水平均较高，且随病情加重而升高。VWF活性也升高，但与VWF抗原水平不成比例。ADAMTS13活性和特异性活性随疾病加重而降低。cVWF在健康对照组和稳定型肝硬化患者中检测不到，但在失代偿性肝硬化、急性肝衰竭或损伤以及急性慢性肝衰竭患者中升高。cVWF水平与d -二聚体相关，但与纤溶蛋白-α2-抗纤溶蛋白复合物或VWF活性无关。结论cvwf在失代偿性肝硬化、急性肝功能衰竭或损伤、急性伴慢性肝功能衰竭患者中可检测到，而在稳定型肝硬化或健康人中未检测到。它与d -二聚体的关联支持与纤溶激活的联系。这些发现表明cVWF可能反映了晚期肝病患者的疾病严重程度或持续的微血管血栓形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Plasmin-mediated proteolysis of von Willebrand factor in patients with acute and chronic liver disease

Background

In patients with acute and chronic liver disease, von Willebrand factor (VWF) antigen levels are markedly elevated, whereas a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS13) activity is often reduced. The role of VWF proteolysis by other proteases, such as plasmin, remains unclear.

Objectives

To investigate whether plasmin-mediated VWF cleavage occurs in patients with acute and chronic liver disease and to assess its association with VWF parameters, ADAMTS13 activity, and fibrinolytic markers.

Methods

Plasma samples from 191 patients with stable or decompensated cirrhosis, acute liver failure or acute liver injury, acute-on-chronic liver failure, or sepsis without underlying chronic liver disease and 41 healthy controls were analyzed. VWF antigen and collagen-binding activity, ADAMTS13 antigen and activity, ADAMTS13-cleaved VWF, plasmin-cleaved VWF (cVWF), plasmin-α2-antiplasmin complexes, and D-dimer were measured by ELISA.

Results

VWF antigen levels were higher in all patient groups and increased with disease severity. VWF activity was also elevated but was not proportional to VWF antigen level. ADAMTS13 activity and specific activity decreased with worsening disease. cVWF was undetectable in healthy controls and patients with stable cirrhosis but was increased in patients with decompensated cirrhosis, acute liver failure or injury, and acute-on-chronic liver failure. cVWF levels correlated with D-dimer but not with plasmin-α2-antiplasmin complexes or VWF activity.

Conclusion

cVWF is detectable in patients with decompensated cirrhosis, acute liver failure or injury, and acute-on-chronic liver failure but not in those with stable cirrhosis or healthy individuals. Its association with D-dimer supports a link with fibrinolytic activation. These findings suggest that cVWF may reflect disease severity or ongoing microvascular thrombosis in patients with advanced liver disease.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊