Assessment of hemostatic disturbances in women with established rheumatoid arthritis

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.

Detection of Citrullinated Fibrin in Plasma Clots of Rheumatoid Arthritis Patients and Its Relation to Altered Structural Clot Properties, Disease-Related Inflammation and Prothrombotic Tendency

“…Some studies have indicated that thin fibrin fibers have higher tensile strength than thicker fibers, concluding that dense networks consisting of predominantly thin fibers are more resistant to degradation (32). Fibrin networks of this nature in RA were observed by Vrancic et al (33). However, study by Buclay et al (34) concluded that thicker fibers are more resistant to plasmin degradation than thinner fibers, owing to their ability to elongate during lysis.…”

Evaluation of global haemostatic assays and fibrin structure in patients with pre‐eclampsia

“…Two additional parameters were also measured: the overall coagulation potential (OCP), which is the Abs‐sum under the fibrin aggregation curve obtained without t‐PA addition and the overall fibrinolysis potential (OFP), which is calculated using the equation: OFP (%) = ((OCP‐OHP)/OCP) × 100. The intra‐ and interassay CVs for the normal plasma pool for OHP were 1.61% and 6.83%, while for OCP they were 1.25% and 5.75%, respectively …”

The Silence Speaks, but We Do Not Listen: Synonymous c.1824C>T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor

“…The controls were used to verify the observation that both cases and controls included from the emergency department displayed hypercoagulable profiles. They were also used to calculate 95th percentile ranges for the 2019 modification of the OHP for study III 166 . Healthy blood donors were also collected for study IV and V. For study IV, 432 Serbian donors, with no thrombotic disorder, family history or known thrombophilia.…”

“…The 2001 protocol 161 was used in study II and the OCP, OHP and OFP in study IV. The 2019 protocol 166 was used in III and for the turbidity times in study IV. The ETP results and OHP results from study III were normalized against standard human plasma, giving results in %.…”