Accelerated Spatial Fibrin Growth and Impaired Contraction of Blood Clots in Patients with Rheumatoid Arthritis.

Alina D Peshkova,Rustem I Litvinov,Timur B Sibgatullin,Tatiana A Evdokimova,John W Weisel,Fazoil I Ataullakhanov

doi:10.3390/ijms21249434

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease associated with thrombotic complications. To elucidate pathogenic mechanisms, hemostatic disorders in RA were correlated with other laboratory and clinical manifestations. Hemostasis was assessed using relatively new complementary tests, the spatial growth of a plasma clot (Thrombodynamics assay), and contraction of whole blood clots. Platelet functionality was assessed with flow cytometry that quantified the expression of P-selectin and the fibrinogen-binding capacity of platelets before and after activation with a thrombin receptor-activating peptide. Parameters of fibrin clot growth and the kinetics of contraction of blood clots were significantly altered in patients with RA compared to the control group. In Thrombodynamics measurements, an increase in the clot growth rate, size, and optical density of plasma clots altogether indicated chronic hypercoagulability. The rate and extent of blood clot contraction in patients with RA was significantly reduced and associated with platelet dysfunction revealed by an impaired response to activation. Changes in the parameters of clot growth and contraction correlated with the laboratory signs of systemic inflammation, including hyperfibrinogenemia. These results confirm the pathogenic role of hemostatic disorders in RA and support the validity of fibrin clot growth and the blood clot contraction assay as indicators of a (pro)thrombotic state.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation associated with pain, edema, and deformation in joints, resulting in immobility and disability [1]
The results show that the parameters of the Thrombodynamics assay and contraction of blood clots in patients with RA are significantly altered compared to healthy donors
The blood clot contraction assay shows a substantial decrease in the extent of clot contraction, median velocity, the area under the kinetic curve, and a longer lag time in patients with RA compared with the control group

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation associated with pain, edema, and deformation in joints, resulting in immobility and disability [1]. RA is not a direct cause of thrombosis, chronic inflammation in RA together with prothrombotic changes in blood composition and endothelial dysfunction lead to the development of atherothrombosis [8]. Inflammation of a joint is accompanied by production and secretion into the blood of cytokines, which induce a prothrombotic state by activating endothelium, resulting in expression of tissue factor, as well as inhibition of the fibrinolysis and protein C pathways [5,10]. All of the above provides mechanistic evidence that RA is a risk factor for thrombotic complications that lead to relatively high rates of premature mortality from cardiovascular diseases in patients with early seropositive arthritis [9]

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