Aetiopathogenesis
Thrombin generation potential is enhanced in systemic sclerosis: impact of selected endothelial biomarkers
P. Kuszmiersz1, R. Pacholczak-Madej2, A. Siwiec3, M. Celińska-Lowenhoff4, T. Iwaniec5, J. Kosałka-Węgiel6, L. Zaręba7, S. Bazan-Socha8, J. Dropiński9
- Rheumatology and Immunology Clinic, University Hospital, Cracow, Poland.
- Department of Anatomy, Jagiellonian University Medical College, Cracow, and National Cancer Institute, Maria Skłodowska-Curie Memorial Institute, Kraków Branch, Poland.
- Rheumatology and Immunology Clinic, University Hospital, Cracow, Poland.
- Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland.
- Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland.
- Rheumatology and Immunology Clinic, University Hospital, Cracow, and Department of Rheumatology and Balneology, Jagiellonian University Medical College, Cracow, Poland.
- Interdisciplinary Centre for Computational Modeling, University of Rzeszow, Poland.
- Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland.
- Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland. jerzy.dropinski@uj.edu.pl
CER13954
2021 Vol.39, N°4 ,Suppl.131
PI 0013, PF 0019
Aetiopathogenesis
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PMID: 33769265 [PubMed]
Received: 19/08/2020
Accepted : 19/11/2020
In Press: 24/03/2021
Published: 28/07/2021
Abstract
OBJECTIVES:
Systemic sclerosis (SSc) is a rare immune-mediated heterogenous entity characterised by excessive tissue fibrosis and vascular injury. Recently, increased risk of thromboembolic events has been documented in that disease. Our aim was to investigate prothrombotic plasma properties together with selected laboratory biomarkers of endothelial injury in SSc.
METHODS:
In 56 clinically stable SSc patients and 67 well-matched controls we assessed plasma thrombin generation profile and measured circulating vascular cell adhesion molecule-1 (VCAM-1), cellular fibronectin (cFN), and thrombomodulin, as well as analysed their relationships with disease clinical parameters and autoimmune antibodies profile.
RESULTS:
SSc was characterised by 18.3% increased endogenous thrombin potential (ETP), 14.5% higher thrombin peak (p<0.001 both, also after adjustment for potential confounders), and similar endothelial damage biomarkers, as compared to controls. Surprisingly, raised thrombin generation was related to the lower thrombomodulin and VCAM-1. Inflammatory markers, factor VIII activity, and blood eosinophilia predicted positively ETP, whereas platelet count and thrombomodulin had negative impact on that parameter in a multiple regression model. Intriguingly, patient group had also 6.7% extended lag-time (p=0.01 after adjustment for confounders) which was independently determined by higher thrombomodulin and cFN, as well as lower VCAM-1. Former cyclophosphamide therapy, thus more severe type of the disease was referred to the increased thrombin generation.
CONCLUSIONS:
SSc is characterised by enhanced thrombin generation potential which might contribute to the higher risk of thromboembolic events in that disease. Endothelium may play hereby an additional role, although large observational and experimental studies are needed to verify this hypothesis.
