Aleksandra Vranic1, Iva Pruner2, Mirjana Veselinovic3, Nida Soutari4, Anica Petkovic1, Vladimir Jakovljevic5,6, Aleksandra Antovic7,8. 1. Faculty of Medical Sciences, Department of Pharmacy, University of Kragujevac, Kragujevac, Serbia. 2. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 3. Faculty of Medical Sciences, Department of Internal Medicine, University of Kragujevac, Kragujevac, Serbia. 4. Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden. 5. Faculty of Medical Sciences, Department of Physiology, University of Kragujevac, Kragujevac, Serbia. 6. 1st Moscow State Medical, University IM Sechenov, Department of Human Pathology, Moscow, Russia. 7. Department of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden. aleksandra.antovic@ki.se. 8. Academic Specialist Center, Center for Rheumatology, Stockholm Health Services, Stockholm, Sweden. aleksandra.antovic@ki.se.
Abstract
OBJECTIVES: This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. METHOD: Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. RESULTS: The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients. CONCLUSIONS: Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting. Key Points • Extensive assessment points towards persistent coagulation activation in premenopausal women with established rheumatoid arthritis. • Impaired thrombin generation and fibrin formation are associated with menopause in healthy women, while rheumatoid arthritis closes the gap within patients regarding menopause. • Fibrin morphology is unfavorably altered and fibrinolysis is decreased in patients with established rheumatoid arthritis. • Increased activity of thrombin activatable fibrinolysis inhibitor (TAFI) may contribute to impaired fibrinolysis in patients with rheumatoid arthritis.
OBJECTIVES: This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. METHOD: Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. RESULTS: The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RApatients compared with the postmenopausal RApatients. SEM images showed denser clots composed of thinner fibers in samples from RApatients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RApatients. CONCLUSIONS: Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting. Key Points • Extensive assessment points towards persistent coagulation activation in premenopausal women with established rheumatoid arthritis. • Impaired thrombin generation and fibrin formation are associated with menopause in healthy women, while rheumatoid arthritis closes the gap within patients regarding menopause. • Fibrin morphology is unfavorably altered and fibrinolysis is decreased in patients with established rheumatoid arthritis. • Increased activity of thrombin activatable fibrinolysis inhibitor (TAFI) may contribute to impaired fibrinolysis in patients with rheumatoid arthritis.
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