Lytic Susceptibility, Structure, and Mechanical Properties of Fibrin in Systemic Lupus Erythematosus

Abstract

Among complications of systemic lupus erythematosus (SLE), thrombotic events are relatively common and contribute significantly to the morbidity and mortality rates. An increased risk of thrombosis in various diseases has been shown to be associated with the lytic stability and mechanical stiffness of the fibrin clot determined by its structure. Here we studied alterations of the fibrin clot properties in relation to disease severity in SLE patients. Plasma clots from 28 SLE patients were characterized by the kinetics of formation and fibrinolytic dissolution (using dynamic turbidimetry), the network and fiber ultrastructure (scanning electron microscopy), viscoelasticity (shear rheometry), and the rate and degree of crosslinking (Western blotting) correlated with the disease activity, blood composition, and compared to clotting of pooled normal human plasma. Clots made from plasma of SLE patients were lysed faster with exogenous t-PA than control clots from normal plasma without a significant difference between those from active (SLEDAI>4) and inactive (SLEDAI<4) SLE patients. Clots from the blood of patients with active SLE were characterized by significantly slower onset, but faster rate of fibrin polymerization and a higher optical density due to thicker fibers compared to those from inactive SLE and control pooled normal plasma. The rheological parameters of the clots (storage and loss moduli) were significantly increased in the active SLE patients along with enhanced fibrin crosslinking and hyperfibrinogenemia. The structural and rheological alterations displayed a strong positive correlation with high fibrinogen levels and other laboratory markers of immune inflammation. In conclusion, changes in the blood composition associated with active systemic inflammation in SLE cause significant alterations in the lytic resistance of fibrin clots associated with changes in polymerization kinetics, viscoelastic properties, and structure. The formation of more rigid prothrombotic fibrin clots in the plasma of SLE patients is likely due to the inflammatory hyperfibrinogenemia and greater extent of crosslinking. However, the higher susceptibility of the SLE clots to fibrinolysis may be a protective and/or compensatory mechanism that reduces the risk of thrombotic complications and improves patient outcomes.

Systemic lupus erythematosus combined with primary hyperfibrinolysis and protein C and protein S deficiency: A case report

“…SLE patients with positive APL are prone to thromboembolism. The rheological parameters of clots were significantly increased in active SLE patients along with enhanced fibrin crosslinking and hyperfibrinogenemia[ 7 ]. Impaired fibrinolysis has been reported in patients with SLE and may contribute to both the development of hypercoagulability and an increased risk of thrombosis[ 8 ].…”

Changes in the Parameters of Thrombodynamics and Blood Clot Contraction in Patients With Rheumatoid Arthritis

“…Высокая концентрация фибриногена в крови пациентов с РА, выявляемая в том числе по повышению оптической плотности сгустка в тесте тромбодинамики, может быть дополнительной причиной уменьшения степени КСК [19]. Важно отметить, что повышение плотности фибриновой сети и изменение ее структуры [38] при гиперфибриногенемии может способствовать снижению проницаемости фибриновой сети для фибринолитичских ферментов, дополнительно увеличивая протромботический потенциал [29].…”

Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation

“…Many factors in the blood affect the outcome of fibrin clot formation and its characteristics [37]. Further, some pathologies are characterized by fibrin clots that have thicker fibers compared to healthy controls, but these clots also have lower porosity [38].…”