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Accelerated Spatial Fibrin Growth and Impaired Contraction of Blood Clots in Patients with Rheumatoid Arthritis
Authors:Alina D Peshkova  Tatiana A Evdokimova  Timur B Sibgatullin  Fazoil I Ataullakhanov  Rustem I Litvinov  John W Weisel
Affiliation:1.Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia; (A.D.P.); (T.A.E.); (R.I.L.);2.Department of Rheumatology, University Hospital, Kazan Federal University, Kazan 420008, Russia;3.Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow 119991, Russia;4.Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
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.
Keywords:rheumatoid arthritis  blood coagulation  hypercoagulability  contraction of blood clots
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