Репозиторий Университета

© 2018 Elsevier Ltd The space-filling fibrin network is a major part of clots and thrombi formed in blood. Fibrin polymerization starts when fibrinogen, a plasma protein, is proteolytically converted to fibrin, which self-assembles to form double-stranded protofibrils. When reaching a critical length, these intermediate species aggregate laterally to transform into fibers arranged into branched fibrin network. We combined multiscale modeling in silico with atomic force microscopy (AFM) imaging to reconstruct complete atomic models of double-stranded fibrin protofibrils with γ-γ crosslinking, A:a and B:b knob-hole bonds, and αC regions—all important structural determinants not resolved crystallographically. Structures of fibrin oligomers and protofibrils containing up to 19 monomers were successfully validated by quantitative comparison with high-resolution AFM images. We characterized the protofibril twisting, bending, kinking, and reversibility of A:a knob-hole bonds, and calculated hydrodynamic parameters of fibrin oligomers. Atomic structures of protofibrils provide a basis to understand mechanisms of early stages of fibrin polymerization. Zhmurov et al. used 27 relevant crystal structures to computationally reconstruct the full-atomic models of fibrin oligomers and protofibrils, which correlate with high-resolution atomic force microscopy images. The structures contain much valuable information for understanding the early stages of fibrin polymerization.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Aim of the study. To compare the effects of tranexamic acid (TXA), factor XIII concentrate (FXIII) and fibrinogen concentrate on clot formation and fibrinolytic resistance in the in vitro model of hyperfibrinolysis induced by tissue-(tPA) vs urokinase-type (uPA) plasminogen activators. Materials and methods. Citrated whole blood from 28 adult healthy volunteers was supplemented with 10 μg/ mL TXA, 2 lU/mL FXIII, or 3 mg/mL fibrinogen concentrate. Hyperfibrinolysis was induced by spiking the blood with PA or uPA at their half-maximal effective concentrations (90 and 33 lU/mL, respectively). Clotting was induced by recalcification and addition of tissue factor and monitored using rotation thromboelastometry. Results. The use of TXA increased maximal clot firmness in the presence of tPA and markedly inhibited clot lysis in the presence of any of the plasminogen activators. Supplementation of blood with FXIII significantly increased clot firmness and improved fibrinolytic resistance in the presence of either PA or uPA. Supplementation with fibrinogen concentrate elicited a strikingly different effect on clot formation and lysis depending on the type of plasminogen activator. In the presence of tPA, fibrinogen concentrate significantly increased clot firmness and attenuated clot lysis. In contrast, in the presence of uPA, the use of fibrinogen markedly reduced clot firmness and promoted clot lysis. Similar effects of fibrinogen concentrate were observed in platelet-rich and microparticles-free plasma. Conclusion. In hyperfibrinolysis, effect of the hemostatic drugs significantly depends on the type of plasminogen activator used. Therefore, mechanisms of hyperfibrinolysis should be taken into consideration while administering hemostatic drugs.

According to current guidelines, non-sedative H1-antihistamines (nsAH) are the first-line therapy of chronic spontaneous urticaria (CSU). But even up-dosed antihistamines (to four times the standard dose) produce symptom resolution in less than 50% of patients. Biomarkers that can predict the response to nsAH are still unknown. We carried out a prospective study and used discriminant analysis to evaluate the combination of D-dimer, fibrinogen, C-reac- tive protein and ESR values for predicting the outcome of treatment with levocetirizine in 84 CSU patients. We found that elevation of these parameters is associated with more active disease, low quality of life and lack of response to standard doses of levocetirizine. Thus, eval-uation of these markers may be considered useful before starting treatment with nsAH. The mechanisms behind the increase in these parameters in CSU patients need to be elucidated in further studies.

According to current guidelines, non-sedative H1-antihistamines (nsAH) are the first-line therapy of chronic spontaneous urticaria (CSU). But even up-dosed antihistamines (to four times the standard dose) produce symptom resolution in less than 50% of patients. Biomarkers that can predict the response to nsAH are still unknown. We carried out a prospective study and used discriminant analysis to evaluate the combination of D-dimer, fibrinogen, C-reac- tive protein and ESR values for predicting the outcome of treatment with levocetirizine in 84 CSU patients. We found that elevation of these parameters is associated with more active disease, low quality of life and lack of response to standard doses of levocetirizine. Thus, eval-uation of these markers may be considered useful before starting treatment with nsAH. The mechanisms behind the increase in these parameters in CSU patients need to be elucidated in further studies.