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CC BY-NC-ND 4.0 · Thromb Haemost 2023; 123(09): 880-891
DOI: 10.1055/s-0043-1768712
Coagulation and Fibrinolysis

Antithrombin Deficiency Is Associated with Prothrombotic Plasma Fibrin Clot Phenotype

Joanna Natorska 
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
,
Javier Corral 
3   Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, IMIB, CIBERER-ISCIII, Universidad de Murcia, Murcia, Spain
,
Maria Eugenia de la Morena-Barrio 
3   Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, IMIB, CIBERER-ISCIII, Universidad de Murcia, Murcia, Spain
,
Carlos Bravo-Pérez 
3   Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, IMIB, CIBERER-ISCIII, Universidad de Murcia, Murcia, Spain
,
Zsuzsa Bagoly 
4   Division of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
,
Zsuzsanna Bereczky 
4   Division of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
,
Jacek Treliński 
5   Department of Haemostasis Disorders, Medical University of Lodz, Łódź, Poland
6   Department of Haematology, Copernicus Memorial Hospital, Łódź, Poland
,
Michał Witkowski 
6   Department of Haematology, Copernicus Memorial Hospital, Łódź, Poland
,
Adrianna Klajmon 
2   Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Kraków, Poland
,
Anetta Undas 
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
,
Michał Ząbczyk 
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
› Institutsangaben Funding This work was supported by the Polish National Science Centre (UMO-2018/31/D/NZ5/01299), Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional -ISCIII & FEDER- (PI21/00174), and by the Hungarian Scientific Research Fund (OTKA K-139293 and FK-128582).
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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.

Keywords

antithrombin deficiency - fibrin clot - fibrinolysis - thrombin generation - venous thromboembolism

Authors' Contribution

Conception and design of the study: M. Z.; data collection, analysis, and interpretation: J. N., J. C., M. E. M.-B., C. B.-P., Z. Ba., Z. Be., J. T., M. W., A. K., and A. U.; drafting the article: J. N. and M. Z.; revising the article: J. C., M. E. M.-B., C. B.-P., Z. Ba., Z. Be., J. T., M. W., A. K., and A. U.


Supplementary Material



Publikationsverlauf

Eingereicht: 09. Dezember 2022

Angenommen: 26. März 2023

Artikel online veröffentlicht:
18. Mai 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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