SummaryImmunoglobulin G (IgG) isolated from normal human blood plasma stabilizes the structure of perfused crosslinked fibrin and prolongs the time for its dissolution with plasmin, when the fibrin surface is exposed to 500 s-1 shear rate flow. The IgG from patients suffering in antiphospholipid syndrome with thrombotic complications exerts even stronger antifibrinolytic effect. A patient, whose IgG does not affect the fibrin dissolution with plasmin, displays a bleeding tendency. The shear stress-induced disassembly of the fibrin clots containing IgGs with antifibrinolytic potency occurs at a much more advanced stage of fibrin digestion, as evidenced by the electrophoretic pattern of the ureatreated samples. The antifibrinolytic effects are also produced under static conditions and these are caused by the variable portion of the IgG molecules (fragment Fab), whereas the constant part (fragment Fc) has no inhibitory effect. The IgGs with antifibrinolytic properties do not affect directly the plasmin activity in amidolytic assay, but the IgGs from APS patients obliterate the competition of the fibrin and the peptidyl-p-nitroanilide for the protease in the same assay system suggesting interference of the IgGs with the plasmin action on the fibrin substrate. Thus, the correlation of the clinical symptoms with the effect of the isolated IgG on the dissolution of perfused fibrin clots supports a physiological and a pathological role of IgG in the fibrinolytic process related to the variability of the cross-reactions of immunoglobulins with fibrin, fibrin degradation products or fibrin-plasmin complexes.

The Coronavirus Disease 2019 (COVID-19) pandemic and the measures of social distancing and national lockdown had a significant impact on everyday life. Individuals with BVI (blindness and visual impairment) are assumed to face increased barriers in numerous domains of their lives. This online survey research investigates, among Hungarian adults with BVI ( N = 132), the impact of the lockdown on their access to shopping, daily support needs, access to remote studies of higher education or work, and leisure habits. Respondents accounted for negative impacts of the lockdown on their participation and independence in all research topics. Issues of accessibility were common both concerning shopping for essential goods and access to remote study and work.

Myosin modulates the fibrinolytic process as a cofactor of the tissue plasminogen activator and as a substrate of plasmin. We report now that myosin is present in arterial thrombi and it forms reversible noncovalent complexes with fibrinogen and fibrin with equilibrium dissociation constants in the micromolar range (1.70 and 0.94 M, respectively). Competition studies using a peptide inhibitor of fibrin polymerization (glycl-prolyl-arginyl-proline [GPRP]) indicate that myosin interacts with domains common in fibrinogen and fibrin and this interaction is independent of the GPRP-binding polymerization site in the fibrinogen molecule. An association rate constant of 1.81 ؋ 10 2 M ؊1 ⅐ s ؊1 and a dissociation rate constant of 3.07 ؋ 10 ؊4 s ؊1 are determined for the fibrinogen-myosin interaction. Surface plasmon resonance studies indicate that fibrin serves as a matrix core for myosin aggregation. The fibrin clots equilibrated with myosin are stabilized against dissolution initiated by plasminogen and tissuetype plasminogen activator (tPA) or urokinase (at fibrin monomer-myosin molar ratio as high as 30) and by plasmin under static and flow conditions (at fibrin monomer-myosin molar ratio lower than 15).Myosin exerts similar effects on the tPAinduced dissolution of blood plasma clots. Covalent modification involving factor XIIIa does not contribute to this stabilizing effect; myosin is not covalently attached to the clot by the time of complete cross-linking of fibrin. Thus, our in vitro data suggest that myosin detected in arterial thrombi binds to the polymerized fibrin, in the bound form its tPA-cofactor properties are masked, and the myosin- IntroductionThe appropriate timing and localization of the proteolytic removal of the fibrin clots in the vascular bed is based on elaborate regulatory mechanisms that determine the availability of fibrinolytic proteases at the level of plasminogen activation 1 and inactivation of the enzymes. 2 Quantitative 3,4 and morphologic 5 data have revealed the importance of the structure of the fibrin substrate in determining the efficiency of fibrinolysis; the fiber diameter, the pore size of the gel, and the frequency of branching points profoundly affect the rate of fibrin dissolution. In experimental models it is rather convenient to modify the structural characteristics of the fibrin gel by changing the concentrations of thrombin and fibrinogen when fibrin is generated 6,7 or the ionic strength at polymerization 4,8 for evaluation of the efficiency of fibrinolysis on various fibrin substrates. In vivo, however, fibrinogen, the precursor of fibrin, circulates in blood surrounded by cells and proteins. Thus, when thrombin converts it to fibrin, the polymerization occurs in a milieu highly enriched in macromolecules. The fibrin assembly is definitely modified by the presence of plasma proteins (eg, albumin 9 ), cellular elements (eg, erythrocytes 10 ), or specific proteins of isolated compartments (eg, amyloid ␤-protein 11 ). This modification can be attributed to the effect of vo...

The contribution of neutrophil leukocyte elastase (NE) to in vivo thrombolysis is still an open question. The present study examines the impact of variable levels of alpha1-proteinase inhibitor (alpha1-PI) (the major plasma inhibitor of NE) on fibrinolysis within the setting of thromboembolic diseases. Blood samples were taken from 56 patients with pulmonary thromboembolism prior to treatment. alpha1-PI and alpha1-PI-NE complex were measured in the serum and plasma with immunoturbidimetric and enzyme-linked immunosorbent assay (ELISA) methods, respectively. The fibrinolytic potential [spontaneous, tissue-type plasminogen activator (tPA) induced, and plasmin induced] of the plasma was evaluated in vitro with turbidimetric clot lysis assay. Correlation analysis (Pearson product-moment correlation coefficient, r) of the turbidimetric lysis parameters and the blood levels of alpha1-PI and alpha1-PI-NE complex was carried out. Fibrinolysis is slower in clots prepared from plasma containing elevated levels of alpha1-PI and alpha1-PI-NE complex. The maximal turbidity of the plasma clots shows significant correlation with the alpha1-PI level (r=0.39, p=0.003) and the correlation of the maximal turbidity and the tPA-induced lysis time is also significant (r=0.77, p<0.001). The lysis time correlates with the plasma level of alpha1-PI-NE complex, if fibrinolysis is induced with tPA (r=0.37, p=0.02), but not with plasmin (r=0.19, p=0.4). Our study shows that in pulmonary thromboembolism elevated levels of alpha1-PI are associated with suppressed plasma fibrinolytic potential. This effect can be at least partially explained by the coarse fibrin network structure and retarded plasminogen activator-dependent fibrinolysis.