Abstract
ObjectivesThis study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity.MethodNinety 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.ResultsThe 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.ConclusionsOur 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.
Highlights
In addition to the progressive disability secondary to the joint impairment, the increased risk of cardiovascular disease (CVD) is a major issue in patients with rheumatoid arthritis (RA) [1]
RA is associated with most subtypes of CVD, and ischemic heart disease (IHD) and in particular myocardial infarction has been most extensively studied [2]
Disease-related risk factors that potentiate the inflammatory burden are of importance, especially elevated levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) [10, 11], as well as the presence of extra-articular manifestations [12], and high disease activity is associated with low functional status [13, 14]
Summary
In addition to the progressive disability secondary to the joint impairment, the increased risk of cardiovascular disease (CVD) is a major issue in patients with rheumatoid arthritis (RA) [1]. The risk of IHD is increased in both men and women with RA, and it seems to develop rather rapidly after disease onset [3]. Despite improvements in RA treatment and improved disease control, the risk for IHD has remained constant over time [4]. Cardiovascular events are a major cause of mortality in patients with RA [5], and recent studies point towards an increased risk of venous thromboembolism and cerebrovascular disease in RA [6, 7]. The positivity for rheumatoid factor (RF) and antibodies to citrullinated protein antigens (ACPAs) has been associated with the risk of clinically significant CVD in RA [15,16,17]
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