Antithrombin Deficiency Is Associated with Prothrombotic Plasma Fibrin Clot Phenotype

Author:

Natorska Joanna12ORCID,Corral Javier3ORCID,de la Morena-Barrio Maria Eugenia3ORCID,Bravo-Pérez Carlos3ORCID,Bagoly Zsuzsa4ORCID,Bereczky Zsuzsanna4ORCID,Treliński Jacek56ORCID,Witkowski Michał6ORCID,Klajmon Adrianna2ORCID,Undas Anetta12ORCID,Ząbczyk Michał12ORCID

Affiliation:

1. Department of Experimental Cardiac Surgery, Anesthesiology and Cardiology, Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland

2. Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Kraków, Poland

3. Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, IMIB, CIBERER-ISCIII, Universidad de Murcia, Murcia, Spain

4. Division of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

5. Department of Haemostasis Disorders, Medical University of Lodz, Łódź, Poland

6. Department of Haematology, Copernicus Memorial Hospital, Łódź, Poland

Abstract

Background Deficiency of antithrombin increases risk of venous thromboembolism. We hypothesized that antithrombin deficiency affects fibrin clot structure and function. Methods We evaluated 148 patients (age: 38 [32–50] years; 70% women) with genetically confirmed antithrombin deficiency and 50 healthy controls. Fibrin clot permeability (Ks) and clot lysis time (CLT) along with thrombin generation capacity were assessed before and after antithrombin activity normalization in vitro. Results Antithrombin-deficient patients had lower antithrombin activity (−39%) and antigen levels (−23%) compared with controls (both p < 0.01). Prothrombin fragment 1 + 2 levels were 26.5% higher in patients with antithrombin deficiency than in controls along with 94% increased endogenous thrombin potential (ETP) and 108% higher peak thrombin (all p < 0.01). Antithrombin deficiency was associated with 18% reduced Ks and 35% prolonged CLT (both p < 0.001). Patients with type I (n = 65; 43.9%) compared with type II antithrombin deficiency (n = 83; 56.1%) had 22.5% lower antithrombin activity (p < 0.001) and despite similar fibrinogen levels, 8.4% reduced Ks, 18% prolonged CLT, and 30% higher ETP (all p < 0.01). Reduced Ks was associated with lower antithrombin antigen level (β = − 6.1, 95% confidence interval [CI]: −1.7 to −10.5), while prolonged CLT was associated with lower antithrombin antigen (β = − 69.6, 95% CI: −9.6 to −129.7), activity (β = − 2.4, 95% CI: −0.3 to −4.5), higher PAI-1 (β = 12.1, 95% CI: 7.7–16.5), and thrombin-activatable fibrinolysis inhibitor levels (β = 3.8, 95% CI: 1.9–5.7). Addition of exogenous antithrombin reduced ETP (−42%) and peak thrombin (−21%), and improved Ks (+8%) and CLT (−12%; all p < 0.01). Conclusion Our study suggests that enhanced thrombin generation and prothrombotic plasma fibrin clot phenotype can contribute to increased risk of thrombosis in patients with antithrombin deficiency.

Publisher

Georg Thieme Verlag KG

Subject

Hematology

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Fibrin Clot Properties in Cancer: Impact on Cancer-Associated Thrombosis;Seminars in Thrombosis and Hemostasis;2023-06-23

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3