Oxidatively-modified fibrinogen induces platelet aggregation and potentiates ADP-induced platelet aggregation and production of active oxygen forms in zymosan-stimulated leukocytes. Fibrinogen induces IL-8 production in primary culture of endothelial cells from human umbilical vein; the oxidized form of fibrinogen is more active, similarly as during induction of the expression cell adhesion molecules (P-selectin and ICAM-1). Oxidized fibrinogen (10 and 20% oxidation degree) impairs microrheological properties of the blood, sharply reduces erythrocyte deformability, modifies blood viscosity, and reduces suspension stability of the blood. Oxidized fibrinogen modified blood clotting parameters and ADP-, ristocetin-, and collagen-induced platelet aggregation in whole blood. Oxidized fibrinogen disordered the formation of fibrin clot and blood clotting process. Platelet aggregation was activated in response to ADP, but not to ristocetin and collagen, the degree of activation increased in direct proportion to the degree of fibrinogen oxidation. This indicates the "dysregulatory" effect of oxidized fibrinogen on platelets. The formation of platelet complexes with polymorphonuclear leukocytes was intensified in the presence of oxidized fibrinogen; polymorphonuclear leukocyte luminol-dependent fluorescence intensity in the presence of platelets increased after incubation with oxidized fibrinogen in comparison with native fibrinogen. Hence, oxidized fibrinogen plays an important role in the development of atherosclerosis and its complications (thromboses).

We studied the effect of UV-irradiated fibrinogen on blood coagulation. Fibrinogen with oxidation degree of 10% moderately activated the intrinsic pathway, but inhibited the extrinsic pathway of blood coagulation. Fibrinogen with oxidation degree of 20% inhibited both the extrinsic and intrinsic blood coagulation pathways. We revealed disturbances in the formation of fibrin clot with oxidized fibrinogen, suppression of platelet aggregation mediated by collagen receptors, and inhibition of aggregation associated with von Willebrand factor activity. ADP initiated platelet aggregation, which was in direct proportion to the degree of fibrinogen oxidation. Our results indicate that oxidized fibrinogen produces a dysregulatory effect on platelets.

After heart transplantation a number of factors such as pre- and postoperative hypoxia of the myocardium, myocardial failure of the early postoperative period, acute rejection episodes, cytomegalovirus infection, and finally the progressive atherosclerosis of the coronary arteries lead to the development of transplanted heart failure. Severe alterations of the myocardial function at this end stage of the process correspond to incurable cardiomyopathy. The target of plasmapheresis in this case is to decrease the extent of the disturbances in the lipoprotein contents and blood rheology for the improvement of the coronary perfusion of the transplanted heart. Nine patients with 3-7 year survival periods after heart transplantations underwent plasmapheresis twice a year using the Haemonetics PCS-plus machine. 2,100-2,700 ml of plasma was removed. Biochemical data, rheology and coagulation, and the concentration of Sandimmune (Sandoz Pharma Ltd., Basel, Switzerland) were controlled, and radionuclide scintigraphy of the myocardium, coronarographia, and transesophageal ultrasound investigations were completed for these patients. The result was the significant improvement of the coronary perfusion of the myocardium. The level of immunosuppression after the plasmapheresis procedures did not change and therefore did not demand any correction. Thus, we think that plasmapheresis can be an effective method of treatment of posttransplantation cardiomyopathy; the improvement of coronary perfusion decreases the extent of chronic ischemia. Further studies are necessary to answer the question as to whether it is possible to prolong the time before retransplantation with the help of plasmapheresis.

We studied the effect of UV-oxidized fibrinogen with oxidation degrees of 10 and 20% on rheological parameters of the blood. The effect of fibrinogen with 10% oxidation degree was moderate and variable, which attests to its partial compensation with the pool of natural antioxidants. The effect of fibrinogen with 20% oxidation degree was more pronounced. It dramatically decreased deformability of erythrocytes, delayed formation of linear aggregates, accelerated formation of 3D-aggregates, enhanced the total hydrodynamic strength of aggregates, but decreased stability of the largest aggregates. It did not increase plasma viscosity, but enhanced viscosity of the blood at all shear rates. At both degrees of oxidation, suspension stability of the blood decreased, the Caisson viscosity did not change, and the difference between the values of Caisson and asymptotic viscosities markedly increased. On the whole, oxidative fibrinogen produces negative changes in blood rheological parameters, and its effect depends on the degree of oxidation.

Expert Council: Drapkina O. M., Vavilova T. V., Karpov Yu. A., Kobalava Zh. D., Lomakin N. V., Martynov A. I., Roitman E. V., Sychev D. A.Scientific communities: the Russian Society for the Prevention of Non-Communicable Diseases (ROPNIZ), the Russian Scientific Medical Society of Therapists (RNMOT), the Russian Antithrombotic Forum (RAF), the National Association for Thrombosis and Hemostasis (NATH).