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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01626

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

 Rustem I. Litvinov1, 2*, Rosa M. Nabiullina3, Laily D. Zubairova3, Mileusha A. Shakurova2, Izabella A. Andrianova2 and John W. Weisel1
  • 1University of Pennsylvania, United States
  • 2Kazan Federal University, Russia
  • 3Kazan State Medical University, Russia

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.

Keywords: Fibrinogen, Fibrin structure, Fibrin, Fibrinolysis, systemic lupus erythematosus

Received: 18 Mar 2019; Accepted: 01 Jul 2019.

Edited by:

Krasimir Kolev, Semmelweis University, Hungary

Reviewed by:

Anetta I. Undas, Jagiellonian University, Poland
Martin Guthold, Wake Forest University, United States  

Copyright: © 2019 Litvinov, Nabiullina, Zubairova, Shakurova, Andrianova and Weisel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Rustem I. Litvinov, University of Pennsylvania, Philadelphia, United States, litvinov@pennmedicine.upenn.edu