Antithrombin Deficiency Is Associated with Prothrombotic Plasma Fibrin Clot Phenotype.

Autor: Natorska J; Department of Experimental Cardiac Surgery, Anesthesiology and Cardiology, Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland.; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Kraków, Poland., Corral J; Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, IMIB, CIBERER-ISCIII, Universidad de Murcia, Murcia, Spain., de la Morena-Barrio ME; Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, IMIB, CIBERER-ISCIII, Universidad de Murcia, Murcia, Spain., Bravo-Pérez C; Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, IMIB, CIBERER-ISCIII, Universidad de Murcia, Murcia, Spain., Bagoly Z; Division of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Bereczky Z; Division of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Treliński J; Department of Haemostasis Disorders, Medical University of Lodz, Łódź, Poland.; Department of Haematology, Copernicus Memorial Hospital, Łódź, Poland., Witkowski M; Department of Haematology, Copernicus Memorial Hospital, Łódź, Poland., Klajmon A; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Kraków, Poland., Undas A; Department of Experimental Cardiac Surgery, Anesthesiology and Cardiology, Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland.; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Kraków, Poland., Ząbczyk M; Department of Experimental Cardiac Surgery, Anesthesiology and Cardiology, Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland.; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Kraków, Poland.
Jazyk: angličtina
Zdroj: Thrombosis and haemostasis [Thromb Haemost] 2023 Sep; Vol. 123 (9), pp. 880-891. Date of Electronic Publication: 2023 May 18.
DOI: 10.1055/s-0043-1768712
Abstrakt: 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 (K s ) 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 K s 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 K s , 18% prolonged CLT, and 30% higher ETP (all p  < 0.01). Reduced K s 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 K s (+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.
Competing Interests: None declared.
(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/).)
Databáze: MEDLINE
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