Intrinsic pathway activation in patients with antiphospholipid syndrome and healthy controls

IF 3.4 3区 医学 Q2 HEMATOLOGY
Dagmar J.M. van Mourik , Valérie L.B.I. Jansen , Michiel Coppens , Saskia Middeldorp , Hugo ten Cate , Harry R. Büller , Henri M.H. Spronk , Magdolna Nagy , Thijs E. van Mens
{"title":"Intrinsic pathway activation in patients with antiphospholipid syndrome and healthy controls","authors":"Dagmar J.M. van Mourik ,&nbsp;Valérie L.B.I. Jansen ,&nbsp;Michiel Coppens ,&nbsp;Saskia Middeldorp ,&nbsp;Hugo ten Cate ,&nbsp;Harry R. Büller ,&nbsp;Henri M.H. Spronk ,&nbsp;Magdolna Nagy ,&nbsp;Thijs E. van Mens","doi":"10.1016/j.rpth.2025.102694","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Antiphospholipid syndrome (APS) is a thrombotic autoimmune disease. Activation of the intrinsic coagulation pathway contributes to inflammatory and cardiovascular diseases, but its role in APS is unknown. Increased release of neutrophil extracellular traps and reduced effectiveness of direct oral anticoagulants support the hypothesis of increased intrinsic pathway activation in patients with APS, which is relevant considering the ongoing development and clinical testing of intrinsic pathway inhibitors.</div></div><div><h3>Objectives</h3><div>To compare <em>in vivo</em> intrinsic pathway activation of patients with APS and healthy controls.</div></div><div><h3>Methods</h3><div>Patients with APS without recent thrombotic or obstetric events and healthy controls were investigated. ELISAs were used to measure activated coagulation factors in complex with the natural inhibitors antithrombin or C1-esterase inhibitor in plasma. The primary outcome of this study was factor (F)XII activation, which initiates the intrinsic pathway. Secondary outcomes included activation of downstream intrinsic coagulation FXI and FIX.</div></div><div><h3>Results</h3><div>Plasma of 73 patients with APS and 19 healthy controls showed no significant difference in activated FXII-inhibitor complexes. The concentrations of activated FXI and FIX and inhibitor complexes likewise did not differ between the groups. A subanalysis of patients with APS by anticoagulant use showed no difference for FXII and FXI activation.</div></div><div><h3>Conclusion</h3><div>Intrinsic pathway activation in patients with APS without recent thrombotic or obstetric events did not differ significantly compared with healthy controls.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102694"},"PeriodicalIF":3.4000,"publicationDate":"2025-01-01","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/S2475037925000184","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

Abstract

Background

Antiphospholipid syndrome (APS) is a thrombotic autoimmune disease. Activation of the intrinsic coagulation pathway contributes to inflammatory and cardiovascular diseases, but its role in APS is unknown. Increased release of neutrophil extracellular traps and reduced effectiveness of direct oral anticoagulants support the hypothesis of increased intrinsic pathway activation in patients with APS, which is relevant considering the ongoing development and clinical testing of intrinsic pathway inhibitors.

Objectives

To compare in vivo intrinsic pathway activation of patients with APS and healthy controls.

Methods

Patients with APS without recent thrombotic or obstetric events and healthy controls were investigated. ELISAs were used to measure activated coagulation factors in complex with the natural inhibitors antithrombin or C1-esterase inhibitor in plasma. The primary outcome of this study was factor (F)XII activation, which initiates the intrinsic pathway. Secondary outcomes included activation of downstream intrinsic coagulation FXI and FIX.

Results

Plasma of 73 patients with APS and 19 healthy controls showed no significant difference in activated FXII-inhibitor complexes. The concentrations of activated FXI and FIX and inhibitor complexes likewise did not differ between the groups. A subanalysis of patients with APS by anticoagulant use showed no difference for FXII and FXI activation.

Conclusion

Intrinsic pathway activation in patients with APS without recent thrombotic or obstetric events did not differ significantly compared with healthy controls.
抗磷脂综合征患者和健康对照的内在通路激活
背景:抗磷脂综合征(APS)是一种血栓性自身免疫性疾病。内在凝血途径的激活有助于炎症和心血管疾病,但其在APS中的作用尚不清楚。中性粒细胞胞外陷阱释放增加和直接口服抗凝剂有效性降低支持APS患者内在途径激活增加的假设,考虑到内在途径抑制剂的持续开发和临床试验,这是相关的。目的比较APS患者与健康对照者体内内通路的激活情况。方法对近期无血栓或产科事件的APS患者和健康对照组进行调查。采用elisa法测定血浆中活化凝血因子与天然抑制剂抗凝血酶或c1 -酯酶抑制剂的复合物。本研究的主要结果是因子(F)XII激活,它启动了内在途径。次要结局包括下游内在凝血FXI和FIX的激活。结果73例APS患者与19例健康对照者血浆fxii -抑制剂复合物活性差异无统计学意义。激活的FXI和FIX以及抑制剂复合物的浓度同样在两组之间没有差异。对APS患者使用抗凝剂的亚分析显示FXII和FXI激活没有差异。结论近期无血栓或产科事件的APS患者的内在通路激活与健康对照组相比无显著差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
5.60
自引率
13.00%
发文量
212
审稿时长
7 weeks
×
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×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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